American Association for Cancer Research
ccr-23-0609_supplementary_figures_s1-s15_suppfs1-fs15.pdf (1.43 MB)

Supplementary Figures S1-S15 from First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma

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journal contribution
posted on 2023-09-01, 08:21 authored by Xiaojiang Duan, Lei Xia, Zhuochen Zhang, Yanan Ren, Martin G. Pomper, Steven P. Rowe, Xuesong Li, Nan Li, Ning Zhang, Hua Zhu, Zhi Yang, Xinan Sheng, Xing Yang

Figure S1. Synthesis of N188. Figure S2. Mass spectrometry characterization of N188.Figure S3. SPR characterization of N188.Figure S4. Radio-HPLC characterization of 68Ga-N188.Figure S5. Stability of 68Ga-N188 in serum and normal saline. Figure S6. Synthesis of FITC-N188. Figure S7. Mass spectrometry characterization of FITC-N188. Figure S8. Blood routine safety test. Figure S9. Toxicity test of 68Ga-N188. Figure S10. Results of PET/CT dynamic imaging studies in one healthy subject. Figure S11. Pharmacokinetics of 68Ga-N188 in mouse blood. Figure. S12 68Ga-N188 PET/CT imaging with maximum intensity projection (MIP) reconstruction of 12 advanced UC patients with obtained pathological sections. Figure S13. Representative PET/CT images of a patient (No. 3) with advanced urothelial carcinoma. Figure. S14 Comparison of brain metastasis imaging of patient No. 4 using 68Ga-N188, 18F-FDG PET/CT and MRI. Figure. S15 Nectin-4 IHC staining in 12 mUC patients with pathological sections of primary focus.


National Natural Science Foundation of China (NSFC)



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. 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. 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. 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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