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Pilot Study of Nectin-4–Targeted PET Imaging Agent 68Ga-FZ-NR-1 in Triple-Negative Breast Cancer from Bench to First-in-Human | Journal of Nuclear Medicine
<!DOCTYPE html> <html lang="en" dir="ltr" xmlns="http://www.w3.org/1999/xhtml" xmlns:mml="http://www.w3.org/1998/Math/MathML"> <head prefix="og: http://ogp.me/ns# article: http://ogp.me/ns/article# book: http://ogp.me/ns/book#" > <!--[if IE]><![endif]--> <link rel="dns-prefetch" href="//securepubads.g.doubleclick.net" /> <link rel="dns-prefetch" href="//scholar.google.com" /> <meta http-equiv="Content-Type" content="text/html; charset=utf-8" /> <link rel="shortcut icon" href="https://jnm.snmjournals.org/sites/default/files/images/favicon.ico" type="image/vnd.microsoft.icon" /> <meta name="viewport" content="width=device-width, initial-scale=1" /> <link rel="shortlink" href="/node/125556" /> <meta name="article_thumbnail" content="https://jnm.snmjournals.org/content/jnumed/early/2025/02/13/jnumed.124.269024/embed/icon-1.jpg" /> <meta name="type" content="article" /> <meta name="category" content="research-article" /> <meta name="HW.identifier" content="/jnumed/early/2025/02/13/jnumed.124.269024.atom" /> <meta name="HW.pisa" content="jnumed;jnumed.124.269024v1" /> <meta name="DC.Format" content="text/html" /> <meta name="DC.Language" content="en" /> <meta name="DC.Title" content="Pilot Study of Nectin-4–Targeted PET Imaging Agent 68Ga-FZ-NR-1 in Triple-Negative Breast Cancer from Bench to First-in-Human" /> <meta name="DC.Identifier" content="10.2967/jnumed.124.269024" /> <meta name="DC.Date" content="2025-02-13" /> <meta name="DC.Publisher" content="Society of Nuclear Medicine" /> <meta name="DC.Rights" content="© 2025 by the Society of Nuclear Medicine and Molecular Imaging." /> <meta name="DC.AccessRights" content="restricted" /> <meta name="DC.Description" content="Nectin cell adhesion molecule 4 (Nectin-4) is an emerging biomarker for cancer diagnosis and therapy. We developed a Nectin-4–targeted 68Ga-DOTA-Sar10-Nectin-4 (68Ga-FZ-NR-1) PET/CT radiotracer for detecting Nectin-4 expression in a tumor model and in triple-negative breast cancer (TNBC) patients. Methods: A series of Nectin-4–targeted radiotracers—68Ga-FZ-NR-1, 68Ga-DOTA-polyethylene glycol 5-Nectin-4 (68Ga-FZ-NR-2), and 68Ga-DOTA-polyethylene glycol 10-Nectin-4 (68Ga-FZ-NR-3)—were synthesized, and their targeting ability and specificity were evaluated in vitro and in vivo. In vitro experiments were performed in the MDA-MB-468 (Nectin-4–positive) and MDA-MB-231 (Nectin-4–negative) cell lines. PET/CT imaging in tumor models was performed to assess the Nectin-4–targeting ability of the radiotracers. After preclinical experiments and screening, the 68Ga-FZ-NR-1 radiotracer was selected for safety and efficacy evaluation in a first-in-human trial in TNBC patients. Positive lesions were biopsied and analyzed by immunohistochemistry to determine Nectin-4 expression levels. Results: The 3 68Ga-labeled radiotracers exhibited high radiochemical purity, stability, and strong affinity for Nectin-4. In vitro cell uptake studies showed that the radiotracers effectively targeted Nectin-4 in MDA-MB-468 cells, and 68Ga-FZ-NR-1 showed the highest targeting efficacy. In the MDA-MB-468 tumor model, PET/CT imaging showed that 68Ga-FZ-NR-1 was taken up at higher rates than 68Ga-FZ-NR-2 and 68Ga-FZ-NR-3, and it exhibited favorable pharmacokinetics and safety profiles. 68Ga-FZ-NR-1 was thus selected for subsequent clinical trials. 68Ga-FZ-NR-1 PET/CT effectively identified tumors in 9 patients with TNBC, which was confirmed by 18F-FDG PET/CT. Biopsy samples of the tumor lesions revealed that the positive lesions identified by 68Ga-FZ-NR-1 PET/CT corresponded to areas of high Nectin-4 expression. Conclusion: A series of Nectin-4–targeted radiotracers (68Ga-FZ-NR-1, 68Ga-FZ-NR-2, and 68Ga-FZ-NR-3) was developed and evaluated. Preclinical studies demonstrated that 68Ga-FZ-NR-1 can identify tumors with high Nectin-4 expression. In a preliminary clinical study, 68Ga-FZ-NR-1 was used to effectively identify and visualize Nectin-4–expressing tumor lesions in patients with TNBC, which was confirmed by immunohistochemistry. This radiotracer provides a noninvasive approach to the assessment of Nectin-4 and a potential basis for the development of Nectin-4–targeted treatments for TNBC." /> <meta name="DC.Contributor" content="Li Sun" /> <meta name="DC.Contributor" content="Yuyun Sun" /> <meta name="DC.Contributor" content="Ke Zuo" /> <meta name="DC.Contributor" content="Lei Fan" /> <meta name="DC.Contributor" content="Xiao Wang" /> <meta name="DC.Contributor" content="Jianping Zhang" /> <meta name="DC.Contributor" content="Silong Hu" /> <meta name="DC.Contributor" content="Xiaosheng Liu" /> <meta name="DC.Contributor" content="Jindian Li" /> <meta name="DC.Contributor" content="Ye Li" /> <meta name="DC.Contributor" content="Zhiming Shao" /> <meta name="DC.Contributor" content="Xiaoping Xu" /> <meta name="DC.Contributor" content="Aiguo Wu" /> <meta name="DC.Contributor" content="Shaoli Song" /> <meta name="article:published_time" content="2025-02-13" /> <meta name="article:section" content="Molecular Imaging" /> <meta name="citation_title" content="Pilot Study of Nectin-4–Targeted PET Imaging Agent 68Ga-FZ-NR-1 in Triple-Negative Breast Cancer from Bench to First-in-Human" /> <meta name="citation_abstract" lang="en" content="<p>Nectin cell adhesion molecule 4 (Nectin-4) is an emerging biomarker for cancer diagnosis and therapy. We developed a Nectin-4–targeted <sup>68</sup>Ga-DOTA-Sar10-Nectin-4 (<sup>68</sup>Ga-FZ-NR-1) PET/CT radiotracer for detecting Nectin-4 expression in a tumor model and in triple-negative breast cancer (TNBC) patients. <b>Methods:</b> A series of Nectin-4–targeted radiotracers—<sup>68</sup>Ga-FZ-NR-1, <sup>68</sup>Ga-DOTA-polyethylene glycol 5-Nectin-4 (<sup>68</sup>Ga-FZ-NR-2), and <sup>68</sup>Ga-DOTA-polyethylene glycol 10-Nectin-4 (<sup>68</sup>Ga-FZ-NR-3)—were synthesized, and their targeting ability and specificity were evaluated in&nbsp;vitro and in&nbsp;vivo. In vitro experiments were performed in the MDA-MB-468 (Nectin-4–positive) and MDA-MB-231 (Nectin-4–negative) cell lines. PET/CT imaging in tumor models was performed to assess the Nectin-4–targeting ability of the radiotracers. After preclinical experiments and screening, the <sup>68</sup>Ga-FZ-NR-1 radiotracer was selected for safety and efficacy evaluation in a first-in-human trial in TNBC patients. Positive lesions were biopsied and analyzed by immunohistochemistry to determine Nectin-4 expression levels. <b>Results:</b> The 3 <sup>68</sup>Ga-labeled radiotracers exhibited high radiochemical purity, stability, and strong affinity for Nectin-4. In vitro cell uptake studies showed that the radiotracers effectively targeted Nectin-4 in MDA-MB-468 cells, and <sup>68</sup>Ga-FZ-NR-1 showed the highest targeting efficacy. In the MDA-MB-468 tumor model, PET/CT imaging showed that <sup>68</sup>Ga-FZ-NR-1 was taken up at higher rates than <sup>68</sup>Ga-FZ-NR-2 and <sup>68</sup>Ga-FZ-NR-3, and it exhibited favorable pharmacokinetics and safety profiles. <sup>68</sup>Ga-FZ-NR-1 was thus selected for subsequent clinical trials. <sup>68</sup>Ga-FZ-NR-1 PET/CT effectively identified tumors in 9 patients with TNBC, which was confirmed by <sup>18</sup>F-FDG PET/CT. Biopsy samples of the tumor lesions revealed that the positive lesions identified by <sup>68</sup>Ga-FZ-NR-1 PET/CT corresponded to areas of high Nectin-4 expression. <b>Conclusion:</b> A series of Nectin-4–targeted radiotracers (<sup>68</sup>Ga-FZ-NR-1, <sup>68</sup>Ga-FZ-NR-2, and <sup>68</sup>Ga-FZ-NR-3) was developed and evaluated. Preclinical studies demonstrated that <sup>68</sup>Ga-FZ-NR-1 can identify tumors with high Nectin-4 expression. In a preliminary clinical study, <sup>68</sup>Ga-FZ-NR-1 was used to effectively identify and visualize Nectin-4–expressing tumor lesions in patients with TNBC, which was confirmed by immunohistochemistry. This radiotracer provides a noninvasive approach to the assessment of Nectin-4 and a potential basis for the development of Nectin-4–targeted treatments for TNBC.</p>" /> <meta name="citation_abstract" lang="en" scheme="graphical" content="<h3>Visual Abstract</h3> " /> <meta name="citation_journal_title" content="Journal of Nuclear Medicine" /> <meta name="citation_publisher" content="Society of Nuclear Medicine" /> <meta name="citation_publication_date" content="2025/02/13" /> <meta name="citation_mjid" content="jnumed;jnumed.124.269024v1" /> <meta name="citation_id" content="jnumed.124.269024v1" /> <meta name="citation_public_url" content="https://jnm.snmjournals.org/content/early/2025/02/13/jnumed.124.269024" /> <meta name="citation_abstract_html_url" content="https://jnm.snmjournals.org/content/early/2025/02/13/jnumed.124.269024.abstract" /> <meta name="citation_full_html_url" content="https://jnm.snmjournals.org/content/early/2025/02/13/jnumed.124.269024.full" /> <meta name="citation_pdf_url" content="https://jnm.snmjournals.org/content/jnumed/early/2025/02/13/jnumed.124.269024.full.pdf" /> <meta name="citation_issn" content="0161-5505" /> <meta name="citation_issn" content="2159-662X" /> <meta name="citation_doi" content="10.2967/jnumed.124.269024" /> <meta name="citation_pmid" content="39947908" /> <meta name="citation_num_pages" content="7" /> <meta name="citation_article_type" content="Research Article" /> <meta name="citation_section" content="Molecular Imaging" /> <meta name="citation_author" content="Li Sun" /> <meta name="citation_author_institution" content="Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;" /> <meta name="citation_author_institution" content="Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, CAS Key Laboratory of Magnetic Materials and Devices, and Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, China;" /> <meta name="citation_author_institution" content="Zhejiang International Cooperation Base of Biomedical Materials Technology and Application, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Cixi Institute of Biomedical Engineering, Cixi, China;" /> <meta name="citation_author" content="Yuyun Sun" /> <meta name="citation_author_institution" content="Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;" /> <meta name="citation_author_institution" content="Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;" /> <meta name="citation_author_institution" content="Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;" /> <meta name="citation_author_institution" content="Center for Biomedical Imaging, Fudan University, Shanghai, China; and" /> <meta name="citation_author" content="Ke Zuo" /> <meta name="citation_author_institution" content="Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;" /> <meta name="citation_author" content="Lei Fan" /> <meta name="citation_author_institution" content="Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China" /> <meta name="citation_author" content="Xiao Wang" /> <meta name="citation_author_institution" content="Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;" /> <meta name="citation_author" content="Jianping Zhang" /> <meta name="citation_author_institution" content="Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;" /> <meta name="citation_author_institution" content="Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;" /> <meta name="citation_author_institution" content="Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;" /> <meta name="citation_author_institution" content="Center for Biomedical Imaging, Fudan University, Shanghai, China; and" /> <meta name="citation_author" content="Silong Hu" /> <meta name="citation_author_institution" content="Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;" /> <meta name="citation_author_institution" content="Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;" /> <meta name="citation_author_institution" content="Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;" /> <meta name="citation_author_institution" content="Center for Biomedical Imaging, Fudan University, Shanghai, China; and" /> <meta name="citation_author" content="Xiaosheng Liu" /> <meta name="citation_author_institution" content="Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;" /> <meta name="citation_author_institution" content="Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;" /> <meta name="citation_author_institution" content="Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;" /> <meta name="citation_author_institution" content="Center for Biomedical Imaging, Fudan University, Shanghai, China; and" /> <meta name="citation_author" content="Jindian Li" /> <meta name="citation_author_institution" content="Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;" /> <meta name="citation_author_institution" content="Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;" /> <meta name="citation_author_institution" content="Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;" /> <meta name="citation_author_institution" content="Center for Biomedical Imaging, Fudan University, Shanghai, China; and" /> <meta name="citation_author" content="Ye Li" /> <meta name="citation_author_institution" content="Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;" /> <meta name="citation_author_institution" content="Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;" /> <meta name="citation_author_institution" content="Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;" /> <meta name="citation_author_institution" content="Center for Biomedical Imaging, Fudan University, Shanghai, China; and" /> <meta name="citation_author" content="Zhiming Shao" /> <meta name="citation_author_institution" content="Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China" /> <meta name="citation_author" content="Xiaoping Xu" /> <meta name="citation_author_institution" content="Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;" /> <meta name="citation_author_institution" content="Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;" /> <meta name="citation_author_institution" content="Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;" /> <meta name="citation_author_institution" content="Center for Biomedical Imaging, Fudan University, Shanghai, China; and" /> <meta name="citation_author" content="Aiguo Wu" /> <meta name="citation_author_institution" content="Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, CAS Key Laboratory of Magnetic Materials and Devices, and Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, China;" /> <meta name="citation_author_institution" content="Zhejiang International Cooperation Base of Biomedical Materials Technology and Application, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Cixi Institute of Biomedical Engineering, Cixi, China;" /> <meta name="citation_author" content="Shaoli Song" /> <meta name="citation_author_institution" content="Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;" /> <meta name="citation_author_institution" content="Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;" /> <meta name="citation_author_institution" content="Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;" /> <meta name="citation_author_institution" content="Center for Biomedical Imaging, Fudan University, Shanghai, China; 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Allison;citation_title=Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update;citation_pages=2105-2122;citation_volume=36;citation_year=2018;citation_pmid=29846122;citation_doi=10.1200/JCO.2018.77.8738" /> <meta name="citation_reference" content="citation_journal_title=Eur J Nucl Med Mol Imaging.;citation_author=X. Wang;citation_author=W. Liu;citation_author=K. Li;citation_title=PET imaging of PARP expression using 68Ga-labelled inhibitors;citation_pages=2606-2620;citation_volume=50;citation_year=2023;citation_pmid=37145164" /> <meta name="citation_reference" content="citation_journal_title=Eur J Pharmacol.;citation_author=H. Wang;citation_author=D. Sun;citation_author=J. Chen;citation_author=H. Li;citation_author=L. Chen;citation_title=Nectin-4 has emerged as a compelling target for breast cancer;citation_pages=176129;citation_volume=960;citation_year=2023;citation_pmid=38059449" /> <meta name="citation_reference" content="citation_journal_title=Advanced drug delivery reviews;citation_journal_abbrev=Adv Drug Deliv Rev;citation_author=GM. Thurber;citation_author=MM. Schmidt;citation_author=KD. Wittrup;citation_title=Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance.;citation_pages=1421-1434;citation_volume=60;citation_year=2008;citation_issue=12;citation_pmid=18541331;citation_doi=10.1016/j.addr.2008.04.012" /> <meta name="twitter:title" content="Pilot Study of Nectin-4–Targeted PET Imaging Agent 68Ga-FZ-NR-1 in Triple-Negative Breast Cancer from Bench to First-in-Human" /> <meta name="twitter:card" content="summary" /> <meta name="twitter:description" content="Nectin cell adhesion molecule 4 (Nectin-4) is an emerging biomarker for cancer diagnosis and therapy. We developed a Nectin-4–targeted 68Ga-DOTA-Sar10-Nectin-4 (68Ga-FZ-NR-1) PET/CT radiotracer for detecting Nectin-4 expression in a tumor model and in triple-negative breast cancer (TNBC) patients. Methods: A series of Nectin-4–targeted radiotracers—68Ga-FZ-NR-1, 68Ga-DOTA-polyethylene glycol 5-Nectin-4 (68Ga-FZ-NR-2), and 68Ga-DOTA-polyethylene glycol 10-Nectin-4 (68Ga-FZ-NR-3)—were synthesized, and their targeting ability and specificity were evaluated in vitro and in vivo. In vitro experiments were performed in the MDA-MB-468 (Nectin-4–positive) and MDA-MB-231 (Nectin-4–negative) cell lines. PET/CT imaging in tumor models was performed to assess the Nectin-4–targeting ability of the radiotracers. After preclinical experiments and screening, the 68Ga-FZ-NR-1 radiotracer was selected for safety and efficacy evaluation in a first-in-human trial in TNBC patients. Positive lesions were biopsied and analyzed by immunohistochemistry to determine Nectin-4 expression levels. Results: The 3 68Ga-labeled radiotracers exhibited high radiochemical purity, stability, and strong affinity for Nectin-4. In vitro cell uptake studies showed that the radiotracers effectively targeted Nectin-4 in MDA-MB-468 cells, and 68Ga-FZ-NR-1 showed the highest targeting efficacy. In the MDA-MB-468 tumor model, PET/CT imaging showed that 68Ga-FZ-NR-1 was taken up at higher rates than 68Ga-FZ-NR-2 and 68Ga-FZ-NR-3, and it exhibited favorable pharmacokinetics and safety profiles. 68Ga-FZ-NR-1 was thus selected for subsequent clinical trials. 68Ga-FZ-NR-1 PET/CT effectively identified tumors in 9 patients with TNBC, which was confirmed by 18F-FDG PET/CT. Biopsy samples of the tumor lesions revealed that the positive lesions identified by 68Ga-FZ-NR-1 PET/CT corresponded to areas of high Nectin-4 expression. Conclusion: A series of Nectin-4–targeted radiotracers (68Ga-FZ-NR-1, 68Ga-FZ-NR-2, and 68Ga-FZ-NR-3) was developed and evaluated. Preclinical studies demonstrated that 68Ga-FZ-NR-1 can identify tumors with high Nectin-4 expression. In a preliminary clinical study, 68Ga-FZ-NR-1 was used to effectively identify and visualize Nectin-4–expressing tumor lesions in patients with TNBC, which was confirmed by immunohistochemistry. This radiotracer provides a noninvasive approach to the assessment of Nectin-4 and a potential basis for the development of Nectin-4–targeted treatments for TNBC." /> <meta name="og-title" property="og:title" content="Pilot Study of Nectin-4–Targeted PET Imaging Agent 68Ga-FZ-NR-1 in Triple-Negative Breast Cancer from Bench to First-in-Human" /> <meta name="og-url" property="og:url" content="https://jnm.snmjournals.org/content/early/2025/02/13/jnumed.124.269024" /> <meta name="og-site-name" property="og:site_name" content="Journal of Nuclear Medicine" /> <meta name="og-description" property="og:description" content="Nectin cell adhesion molecule 4 (Nectin-4) is an emerging biomarker for cancer diagnosis and therapy. We developed a Nectin-4–targeted 68Ga-DOTA-Sar10-Nectin-4 (68Ga-FZ-NR-1) PET/CT radiotracer for detecting Nectin-4 expression in a tumor model and in triple-negative breast cancer (TNBC) patients. Methods: A series of Nectin-4–targeted radiotracers—68Ga-FZ-NR-1, 68Ga-DOTA-polyethylene glycol 5-Nectin-4 (68Ga-FZ-NR-2), and 68Ga-DOTA-polyethylene glycol 10-Nectin-4 (68Ga-FZ-NR-3)—were synthesized, and their targeting ability and specificity were evaluated in vitro and in vivo. In vitro experiments were performed in the MDA-MB-468 (Nectin-4–positive) and MDA-MB-231 (Nectin-4–negative) cell lines. PET/CT imaging in tumor models was performed to assess the Nectin-4–targeting ability of the radiotracers. After preclinical experiments and screening, the 68Ga-FZ-NR-1 radiotracer was selected for safety and efficacy evaluation in a first-in-human trial in TNBC patients. Positive lesions were biopsied and analyzed by immunohistochemistry to determine Nectin-4 expression levels. Results: The 3 68Ga-labeled radiotracers exhibited high radiochemical purity, stability, and strong affinity for Nectin-4. In vitro cell uptake studies showed that the radiotracers effectively targeted Nectin-4 in MDA-MB-468 cells, and 68Ga-FZ-NR-1 showed the highest targeting efficacy. In the MDA-MB-468 tumor model, PET/CT imaging showed that 68Ga-FZ-NR-1 was taken up at higher rates than 68Ga-FZ-NR-2 and 68Ga-FZ-NR-3, and it exhibited favorable pharmacokinetics and safety profiles. 68Ga-FZ-NR-1 was thus selected for subsequent clinical trials. 68Ga-FZ-NR-1 PET/CT effectively identified tumors in 9 patients with TNBC, which was confirmed by 18F-FDG PET/CT. Biopsy samples of the tumor lesions revealed that the positive lesions identified by 68Ga-FZ-NR-1 PET/CT corresponded to areas of high Nectin-4 expression. Conclusion: A series of Nectin-4–targeted radiotracers (68Ga-FZ-NR-1, 68Ga-FZ-NR-2, and 68Ga-FZ-NR-3) was developed and evaluated. Preclinical studies demonstrated that 68Ga-FZ-NR-1 can identify tumors with high Nectin-4 expression. In a preliminary clinical study, 68Ga-FZ-NR-1 was used to effectively identify and visualize Nectin-4–expressing tumor lesions in patients with TNBC, which was confirmed by immunohistochemistry. This radiotracer provides a noninvasive approach to the assessment of Nectin-4 and a potential basis for the development of Nectin-4–targeted treatments for TNBC." /> <meta name="og-type" property="og:type" content="article" /> <meta name="og-image" property="og:image" content="" /> <link rel="canonical" href="https://jnm.snmjournals.org/content/early/2025/02/13/jnumed.124.269024" /> <meta name="Generator" content="Drupal 7 (http://drupal.org)" /> <link rel="alternate" type="application/pdf" title="Full Text (PDF)" href="/content/early/2025/02/13/jnumed.124.269024.full.pdf" /> <link rel="alternate" type="text/plain" title="Full Text (Plain)" href="/content/early/2025/02/13/jnumed.124.269024.full.txt" /> <link rel="alternate" type="application/vnd.ms-powerpoint" title="Powerpoint" href="/content/early/2025/02/13/jnumed.124.269024.ppt" /> <title>Pilot Study of Nectin-4–Targeted PET Imaging Agent 68Ga-FZ-NR-1 in Triple-Negative Breast Cancer from Bench to First-in-Human | Journal of 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-1472px;padding-left:18px;">Corsican</option><option value="en|hr" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -80px;padding-left:18px;">Croatian</option><option value="en|cs" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -96px;padding-left:18px;">Czech</option><option value="en|da" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -112px;padding-left:18px;">Danish</option><option value="en|nl" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -128px;padding-left:18px;">Dutch</option><option value="en|eo" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -976px;padding-left:18px;">Esperanto</option><option value="en|et" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -576px;padding-left:18px;">Estonian</option><option value="en|tl" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -400px;padding-left:18px;">Filipino</option><option value="en|fi" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -144px;padding-left:18px;">Finnish</option><option value="en|fr" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -160px;padding-left:18px;">French</option><option value="en|fy" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1632px;padding-left:18px;">Frisian</option><option value="en|gl" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -592px;padding-left:18px;">Galician</option><option value="en|ka" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -880px;padding-left:18px;">Georgian</option><option value="en|de" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -176px;padding-left:18px;">German</option><option value="en|el" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -192px;padding-left:18px;">Greek</option><option value="en|gu" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -992px;padding-left:18px;">Gujarati</option><option value="en|ht" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -896px;padding-left:18px;">Haitian Creole</option><option value="en|ha" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1008px;padding-left:18px;">Hausa</option><option value="en|haw" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1488px;padding-left:18px;">Hawaiian</option><option value="en|iw" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -416px;padding-left:18px;">Hebrew</option><option value="en|hi" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -208px;padding-left:18px;">Hindi</option><option value="en|hmn" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1024px;padding-left:18px;">Hmong</option><option value="en|hu" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -608px;padding-left:18px;">Hungarian</option><option value="en|is" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -784px;padding-left:18px;">Icelandic</option><option value="en|ig" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1040px;padding-left:18px;">Igbo</option><option value="en|id" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -432px;padding-left:18px;">Indonesian</option><option value="en|ga" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -736px;padding-left:18px;">Irish</option><option value="en|it" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -224px;padding-left:18px;">Italian</option><option value="en|ja" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -240px;padding-left:18px;">Japanese</option><option value="en|jw" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1056px;padding-left:18px;">Javanese</option><option value="en|kn" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1072px;padding-left:18px;">Kannada</option><option value="en|kk" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1328px;padding-left:18px;">Kazakh</option><option value="en|km" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1088px;padding-left:18px;">Khmer</option><option value="en|ko" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -256px;padding-left:18px;">Korean</option><option value="en|ku" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1504px;padding-left:18px;">Kurdish (Kurmanji)</option><option value="en|ky" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1520px;padding-left:18px;">Kyrgyz</option><option value="en|lo" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1104px;padding-left:18px;">Lao</option><option value="en|la" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1120px;padding-left:18px;">Latin</option><option value="en|lv" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -448px;padding-left:18px;">Latvian</option><option value="en|lt" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -464px;padding-left:18px;">Lithuanian</option><option value="en|lb" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1536px;padding-left:18px;">Luxembourgish</option><option value="en|mk" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -800px;padding-left:18px;">Macedonian</option><option value="en|mg" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1344px;padding-left:18px;">Malagasy</option><option value="en|ms" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -704px;padding-left:18px;">Malay</option><option value="en|ml" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1360px;padding-left:18px;">Malayalam</option><option value="en|mt" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -624px;padding-left:18px;">Maltese</option><option value="en|mi" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1136px;padding-left:18px;">Maori</option><option value="en|mr" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1152px;padding-left:18px;">Marathi</option><option value="en|mn" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1168px;padding-left:18px;">Mongolian</option><option value="en|my" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1296px;padding-left:18px;">Myanmar (Burmese)</option><option value="en|ne" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1184px;padding-left:18px;">Nepali</option><option value="en|no" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -272px;padding-left:18px;">Norwegian</option><option value="en|ps" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1552px;padding-left:18px;">Pashto</option><option value="en|fa" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -672px;padding-left:18px;">Persian</option><option value="en|pl" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -288px;padding-left:18px;">Polish</option><option value="en|pt" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -304px;padding-left:18px;">Portuguese</option><option value="en|pa" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1200px;padding-left:18px;">Punjabi</option><option value="en|ro" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -320px;padding-left:18px;">Romanian</option><option value="en|ru" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -336px;padding-left:18px;">Russian</option><option value="en|sm" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1568px;padding-left:18px;">Samoan</option><option value="en|gd" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1584px;padding-left:18px;">Scottish Gaelic</option><option value="en|sr" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -480px;padding-left:18px;">Serbian</option><option value="en|st" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1392px;padding-left:18px;">Sesotho</option><option value="en|sn" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1600px;padding-left:18px;">Shona</option><option value="en|sd" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1616px;padding-left:18px;">Sindhi</option><option value="en|si" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1376px;padding-left:18px;">Sinhala</option><option value="en|sk" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -496px;padding-left:18px;">Slovak</option><option value="en|sl" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -512px;padding-left:18px;">Slovenian</option><option value="en|so" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1216px;padding-left:18px;">Somali</option><option value="en|es" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -352px;padding-left:18px;">Spanish</option><option value="en|su" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1408px;padding-left:18px;">Sudanese</option><option value="en|sw" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -720px;padding-left:18px;">Swahili</option><option value="en|sv" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -368px;padding-left:18px;">Swedish</option><option value="en|tg" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1424px;padding-left:18px;">Tajik</option><option value="en|ta" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1232px;padding-left:18px;">Tamil</option><option value="en|te" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1248px;padding-left:18px;">Telugu</option><option value="en|th" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -640px;padding-left:18px;">Thai</option><option value="en|tr" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -656px;padding-left:18px;">Turkish</option><option value="en|uk" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -528px;padding-left:18px;">Ukrainian</option><option value="en|ur" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -912px;padding-left:18px;">Urdu</option><option value="en|uz" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1440px;padding-left:18px;">Uzbek</option><option value="en|vi" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -544px;padding-left:18px;">Vietnamese</option><option value="en|cy" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -752px;padding-left:18px;">Welsh</option><option value="en|xh" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1648px;padding-left:18px;">Xhosa</option><option value="en|yi" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -816px;padding-left:18px;">Yiddish</option><option value="en|yo" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1264px;padding-left:18px;">Yoruba</option><option value="en|zu" style="background:url('/sites/all/modules/contrib/gtranslate/gtranslate-files/16l.png') no-repeat scroll 0 -1280px;padding-left:18px;">Zulu</option></select> </div> </div> </div> </div> </div> </div> <div id="zone-menu" class="zone zone-menu clearfix mobile-hidden container-30"> <div class="grid-28 suffix-1 prefix-1 region region-menu region-menu-bg-opaque region-gutters-inner main-menu-active-bg" id="region-menu"> <div class="region-inner region-menu-inner"> <div class="block 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container-30"> </div> </header> <section id="section-content" class="section section-content"> <div id="zone-content" class="zone zone-content clearfix container-30"> <div class="grid-28 suffix-1 prefix-1 region region-content" id="region-content"> <div class="region-inner region-content-inner"> <a id="main-content"></a> <div class="block block-system block-main block-system-main odd block-without-title" id="block-system-main"> <div class="block-inner clearfix"> <div class="content clearfix"> <div class="panel-display panels-960-layout jcore-2col-layout" > <div class="panel-row-wrapper panel-row-first clearfix"> <div class="top-wrapper"> <div class="panel-panel panel-region-top"> <div class="inside"><div class="panel-pane pane-highwire-article-citation" > <div class="pane-content"> <div class="highwire-article-citation highwire-citation-type-highwire-article node125556--5" data-node-nid="125556" id="top-node-125556--61587397297" data-pisa="jnumed;jnumed.124.269024v1" data-pisa-master="jnumed;jnumed.124.269024" data-apath="/jnumed/early/2025/02/13/jnumed.124.269024.atom" data-hw-author-tooltip-instance="highwire_author_tooltip"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-article-title-complete clearfix has-author-tooltip highwire-citation-highwire-article-top-a"> <div class="highwire-cite-overline"><span class="highwire-cite-metadata-article-type highwire-cite-metadata">Research Article</span><span class="separator-pipe"></span><span class="highwire-cite-metadata-art-cat highwire-cite-metadata"><span class="wrapper">Molecular Imaging</span></span></div> <div class="highwire-cite-access"><span class="highwire-citation-access highwire-citation-access-check" data-pisa-id="jnumed;jnumed.124.269024" data-atom-uri="/jnumed/early/2025/02/13/jnumed.124.269024.atom" data-request-view="full"></span></div> <h1 class="highwire-cite-title" id="page-title">Pilot Study of Nectin-4–Targeted PET Imaging Agent <sup>68</sup>Ga-FZ-NR-1 in Triple-Negative Breast Cancer from Bench to First-in-Human</h1> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">Li Sun</span>, <span class="highwire-citation-author" data-delta="1">Yuyun Sun</span>, <span class="highwire-citation-author" data-delta="2">Ke Zuo</span>, <span class="highwire-citation-author" data-delta="3">Lei Fan</span>, <span class="highwire-citation-author" data-delta="4">Xiao Wang</span>, <span class="highwire-citation-author" data-delta="5">Jianping Zhang</span>, <span class="highwire-citation-author" data-delta="6">Silong Hu</span>, <span class="highwire-citation-author" data-delta="7">Xiaosheng Liu</span>, <span class="highwire-citation-author" data-delta="8">Jindian Li</span>, <span class="highwire-citation-author" data-delta="9">Ye Li</span>, <span class="highwire-citation-author" data-delta="10">Zhiming Shao</span>, <span class="highwire-citation-author" data-delta="11">Xiaoping Xu</span>, <span class="highwire-citation-author" data-delta="12">Aiguo Wu</span> and <span class="highwire-citation-author" data-delta="13">Shaoli Song</span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-journal highwire-cite-metadata">Journal of Nuclear Medicine </span><span class="highwire-cite-metadata-date highwire-cite-metadata">February 2025, </span><span class="highwire-cite-metadata-pages highwire-cite-metadata">jnumed.124.269024; </span><span class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.2967/jnumed.124.269024 </span></div> <div class="highwire-cite-extras"><span class="highwire-foxycart-add-to-cart-ahah highwire-foxycart-add-to-cart-ahah" data-text="Add to Cart (%short-price)" data-apath="/jnumed/early/2025/02/13/jnumed.124.269024.atom" data-type="link" data-font-icon="" data-parent-id="14"></span></div> </div> <div id="hw-article-author-popups-top-node-125556--61587397297" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">Li Sun </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;</div><div class='author-affiliation'><span class='nlm-sup'>2</span>Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, CAS Key Laboratory of Magnetic Materials and Devices, and Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, China;</div><div class='author-affiliation'><span class='nlm-sup'>3</span>Zhejiang International Cooperation Base of Biomedical Materials Technology and Application, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Cixi Institute of Biomedical Engineering, Cixi, China;</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Li%2BSun%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Sun%20L&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3ALi%2BSun%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">Yuyun Sun </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;</div><div class='author-affiliation'><span class='nlm-sup'>4</span>Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;</div><div class='author-affiliation'><span class='nlm-sup'>5</span>Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;</div><div class='author-affiliation'><span class='nlm-sup'>6</span>Center for Biomedical Imaging, Fudan University, Shanghai, China; and</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Yuyun%2BSun%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Sun%20Y&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" 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class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Fan%20L&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3ALei%2BFan%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">Xiao Wang </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Xiao%2BWang%2B" target="_blank" class="" data-icon-position="" 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class='author-affiliation'><span class='nlm-sup'>5</span>Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;</div><div class='author-affiliation'><span class='nlm-sup'>6</span>Center for Biomedical Imaging, Fudan University, Shanghai, China; and</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jianping%2BZhang%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Zhang%20J&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AJianping%2BZhang%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on 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class='author-affiliation'><span class='nlm-sup'>5</span>Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;</div><div class='author-affiliation'><span class='nlm-sup'>6</span>Center for Biomedical Imaging, Fudan University, Shanghai, China; and</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Xiaosheng%2BLiu%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Liu%20X&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AXiaosheng%2BLiu%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-8"><div class="author-tooltip-name">Jindian Li </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;</div><div class='author-affiliation'><span class='nlm-sup'>4</span>Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;</div><div class='author-affiliation'><span class='nlm-sup'>5</span>Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;</div><div class='author-affiliation'><span class='nlm-sup'>6</span>Center for Biomedical Imaging, Fudan University, Shanghai, China; and</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Jindian%2BLi%2B" target="_blank" class="" 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class='author-affiliation'><span class='nlm-sup'>5</span>Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;</div><div class='author-affiliation'><span class='nlm-sup'>6</span>Center for Biomedical Imaging, Fudan University, Shanghai, China; and</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Ye%2BLi%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Li%20Y&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AYe%2BLi%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-10"><div class="author-tooltip-name">Zhiming Shao </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>7</span>Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Zhiming%2BShao%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Shao%20Z&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AZhiming%2BShao%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-11"><div class="author-tooltip-name">Xiaoping Xu </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China;</div><div class='author-affiliation'><span class='nlm-sup'>4</span>Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;</div><div class='author-affiliation'><span class='nlm-sup'>5</span>Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China;</div><div class='author-affiliation'><span class='nlm-sup'>6</span>Center for Biomedical Imaging, Fudan University, Shanghai, China; and</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a 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Laboratory of Advanced Theranostic Materials and Technology, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, China;</div><div class='author-affiliation'><span class='nlm-sup'>3</span>Zhejiang International Cooperation Base of Biomedical Materials Technology and Application, Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Cixi Institute of Biomedical Engineering, Cixi, China;</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Aiguo%2BWu%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Wu%20A&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li 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xmlns="http://www.w3.org/1999/xhtml" data-highwire-cite-ref-tooltip-instance="highwire_reflinks_tooltip" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article abstract-view "><span class="highwire-journal-article-marker-start"></span><div class="section graphic-abstract" id="abstract-1"><h2 class="">Visual Abstract</h2><div id="F1" class="fig pos-float type-featured graphic-abstract odd"><div class="highwire-figure"><div class="fig-inline-img-wrapper"><div class="fig-inline-img"><a href="https://jnm.snmjournals.org/content/jnumed/early/2025/02/13/jnumed.124.269024/F1.large.jpg?width=800&height=600&carousel=1" title="" class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-146842379" data-figure-caption="<div class="highwire-markup"></div>" data-icon-position="" data-hide-link-title="0"><span class="hw-responsive-img"><img class="highwire-fragment fragment-image lazyload" alt="Figure" src="data:image/gif;base64,R0lGODlhAQABAIAAAAAAAP///yH5BAEAAAAALAAAAAABAAEAAAIBRAA7" data-src="https://jnm.snmjournals.org/content/jnumed/early/2025/02/13/jnumed.124.269024/F1.medium.gif" width="440" height="409"/><noscript><img class="highwire-fragment fragment-image" alt="Figure" src="https://jnm.snmjournals.org/content/jnumed/early/2025/02/13/jnumed.124.269024/F1.medium.gif" width="440" height="409"/></noscript></span></a></div></div><ul class="highwire-figure-links inline"><li class="download-fig first"><a href="https://jnm.snmjournals.org/content/jnumed/early/2025/02/13/jnumed.124.269024/F1.large.jpg?download=true" class="highwire-figure-link highwire-figure-link-download" title="Download Figure1" data-icon-position="" data-hide-link-title="0">Download figure</a></li><li class="new-tab"><a href="https://jnm.snmjournals.org/content/jnumed/early/2025/02/13/jnumed.124.269024/F1.large.jpg" class="highwire-figure-link highwire-figure-link-newtab" target="_blank" data-icon-position="" data-hide-link-title="0">Open in new tab</a></li><li class="download-ppt last"><a href="/highwire/powerpoint/125613" class="highwire-figure-link highwire-figure-link-ppt" data-icon-position="" data-hide-link-title="0">Download powerpoint</a></li></ul></div></div><p id="p-2"></p></div><div class="section abstract" id="abstract-2"><h2>Abstract</h2><p id="p-3">Nectin cell adhesion molecule 4 (Nectin-4) is an emerging biomarker for cancer diagnosis and therapy. We developed a Nectin-4–targeted <sup>68</sup>Ga-DOTA-Sar10-Nectin-4 (<sup>68</sup>Ga-FZ-NR-1) PET/CT radiotracer for detecting Nectin-4 expression in a tumor model and in triple-negative breast cancer (TNBC) patients. <strong>Methods:</strong> A series of Nectin-4–targeted radiotracers—<sup>68</sup>Ga-FZ-NR-1, <sup>68</sup>Ga-DOTA-polyethylene glycol 5-Nectin-4 (<sup>68</sup>Ga-FZ-NR-2), and <sup>68</sup>Ga-DOTA-polyethylene glycol 10-Nectin-4 (<sup>68</sup>Ga-FZ-NR-3)—were synthesized, and their targeting ability and specificity were evaluated in vitro and in vivo. In vitro experiments were performed in the MDA-MB-468 (Nectin-4–positive) and MDA-MB-231 (Nectin-4–negative) cell lines. PET/CT imaging in tumor models was performed to assess the Nectin-4–targeting ability of the radiotracers. After preclinical experiments and screening, the <sup>68</sup>Ga-FZ-NR-1 radiotracer was selected for safety and efficacy evaluation in a first-in-human trial in TNBC patients. Positive lesions were biopsied and analyzed by immunohistochemistry to determine Nectin-4 expression levels. <strong>Results:</strong> The 3 <sup>68</sup>Ga-labeled radiotracers exhibited high radiochemical purity, stability, and strong affinity for Nectin-4. In vitro cell uptake studies showed that the radiotracers effectively targeted Nectin-4 in MDA-MB-468 cells, and <sup>68</sup>Ga-FZ-NR-1 showed the highest targeting efficacy. In the MDA-MB-468 tumor model, PET/CT imaging showed that <sup>68</sup>Ga-FZ-NR-1 was taken up at higher rates than <sup>68</sup>Ga-FZ-NR-2 and <sup>68</sup>Ga-FZ-NR-3, and it exhibited favorable pharmacokinetics and safety profiles. <sup>68</sup>Ga-FZ-NR-1 was thus selected for subsequent clinical trials. <sup>68</sup>Ga-FZ-NR-1 PET/CT effectively identified tumors in 9 patients with TNBC, which was confirmed by <sup>18</sup>F-FDG PET/CT. Biopsy samples of the tumor lesions revealed that the positive lesions identified by <sup>68</sup>Ga-FZ-NR-1 PET/CT corresponded to areas of high Nectin-4 expression. <strong>Conclusion:</strong> A series of Nectin-4–targeted radiotracers (<sup>68</sup>Ga-FZ-NR-1, <sup>68</sup>Ga-FZ-NR-2, and <sup>68</sup>Ga-FZ-NR-3) was developed and evaluated. Preclinical studies demonstrated that <sup>68</sup>Ga-FZ-NR-1 can identify tumors with high Nectin-4 expression. In a preliminary clinical study, <sup>68</sup>Ga-FZ-NR-1 was used to effectively identify and visualize Nectin-4–expressing tumor lesions in patients with TNBC, which was confirmed by immunohistochemistry. This radiotracer provides a noninvasive approach to the assessment of Nectin-4 and a potential basis for the development of Nectin-4–targeted treatments for TNBC.</p></div><ul class="kwd-group"><li class="kwd"><a href="/keyword/triple-negative-breast-cancer" class="hw-term hw-article-keyword hw-article-keyword-triple-negative-breast-cancer" rel="nofollow">triple-negative breast cancer</a></li><li class="kwd"><a href="/keyword/tnbc" class="hw-term hw-article-keyword hw-article-keyword-tnbc" rel="nofollow">TNBC</a></li><li class="kwd"><a href="/keyword/nectin-4" class="hw-term hw-article-keyword hw-article-keyword-nectin-4" rel="nofollow">Nectin-4</a></li><li class="kwd"><a href="/keyword/radiotracer" class="hw-term hw-article-keyword hw-article-keyword-radiotracer" rel="nofollow">radiotracer</a></li><li class="kwd"><a href="/keyword/petct-imaging" class="hw-term hw-article-keyword hw-article-keyword-pet-ct-imaging" rel="nofollow">PET/CT imaging</a></li><li class="kwd"><a xmlns:default="http://www.w3.org/1999/xhtml" href="/keyword/68ga" class="hw-term hw-article-keyword hw-article-keyword-68ga" rel="nofollow"><sup xmlns:default="http://www.w3.org/1999/xhtml">68</sup>Ga</a></li></ul><div class="section fn-group" id="fn-group-1"><h2>Footnotes</h2><ul><li class="fn" id="fn-1"><p id="p-1">Published online Feb. 13, 2025.</p></li></ul></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2025 by the Society of Nuclear Medicine and Molecular Imaging.</li></ul><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div><a href="https://jnm.snmjournals.org/content/early/2025/02/13/jnumed.124.269024.full" class="hw-link hw-link-article-full-text" data-icon-position="" data-hide-link-title="0">View Full Text</a></div> </div> </div> <div class="panel-separator"></div><div class="panel-pane pane-snippet pane-article-access-text" > <div class="pane-content"> <div class="snippet article-access-text" id="article-access-text"> <div class="snippet-content"> <p>This article requires a subscription to view the full text. 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