2. Academic Validation
  3. First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma

First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma

  • Clin Cancer Res. 2023 Sep 1;29(17):3395-3407. doi: 10.1158/1078-0432.CCR-23-0609.
Xiaojiang Duan # 1,  Lei Xia # 2 3,  Zhuochen Zhang # 1,  Yanan Ren 2,  Martin G Pomper 4,  Steven P Rowe 4,  Xuesong Li 5,  Nan Li 2 3,  Ning Zhang 6,  Hua Zhu 2 3,  Zhi Yang 2 3,  Xinan Sheng 7,  Xing Yang 1 3 8 9 10
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, Peking University First Hospital, Beijing, China.
  • 2 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China.
  • 3 Key Laboratory for Research and Evaluation of Radiopharmaceuticals, National Medical Products Administration (NMPA), Beijing, China.
  • 4 Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
  • 5 Department of Urology, Peking University First Hospital, Beijing, China.
  • 6 Translational Cancer Research Center, Peking University First Hospital, Beijing, China.
  • 7 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
  • 8 Institute of Medical Technology, Peking University Health Science Center, Beijing, China.
  • 9 International Cancer Institute, Peking University Health Science Center, Beijing, China.
  • 10 Yunnan Baiyao Group, Kunming, China.
  • # Contributed equally.
PMID: 37093191 DOI: 10.1158/1078-0432.CCR-23-0609
Abstract

Purpose: Nectin-4 is an emerging biomarker for Cancer diagnosis and therapy. Recently, enfortumab vedotin (EV) was approved by the FDA as the first Nectin-4 targeting antibody-drug conjugate for treating advanced urothelial carcinoma (UC). A PET imaging method to noninvasively quantify Nectin-4 expression level would potentially help to select patients most likely to respond to EV and predict the response.

Experimental design: In this study, we designed a bicyclic peptide-based Nectin-4 targeting radiotracer 68Ga-N188. Initially, we performed preclinical evaluations of 68Ga-N188 in UC cell lines and xenograft mouse models. Next, we performed the translational study in healthy volunteers and a pilot cohort of patients with advanced UC on uEXPLORER total-body PET/CT.

Results: In the preclinical study, 68Ga-N188 showed high affinity to Nectin-4, specific uptake in a Nectin-4(+) xenograft mouse model, and suitable pharmacokinetic and safety profiles. In the translational study, 2 healthy volunteers and 14 patients with advanced UC were enrolled. The pharmacokinetic profile was determined for 68Ga-N188, and the Nectin-4 relative expression level in different organs was quantitatively imaged.

Conclusions: A clear correlation between PET SUV value and Nectin-4 expression was observed, supporting the application of 68Ga-N188 PET as a companion diagnostic tool for optimizing treatments that target Nectin-4. See related commentary by Jiang et al., p. 3259.

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