We recently identified CD46 as a novel therapeutic target in prostate cancer (PCa). In the present study, we developed a novel CD46-targeted positron emission tomography (PET) radiopharmaceutical, [89Zr]DFO-YS5, and evaluated its performance for immunoPET imaging in murine PCa models.
[89Zr]DFO-YS5 was prepared and its in vitro binding affinity for CD46 was measured. ImmunoPET imaging was conducted in male athymic nu/nu mice bearing DU145 (AR-, CD46+, PSMA-) or 22Rv1 (AR+, CD46+, PSMA+) tumors, and NSG mice bearing patient derived adenocarcinoma xenograft LTL-331, and neuroendocrine prostate cancers LTL-331R and LTL-545.
[89Zr]DFO-YS5 binds specifically to the CD46 positive human PCa DU145 and 22Rv1 xenografts. In biodistribution studies, the tumor uptake of [89Zr]DFO-YS5 was 13.3 ± 3.9 % ID/gram and 11.2 ± 2.5 % ID/gram respectively in DU145 and 22Rv1 xenografts 4 days post injection. Notably, [89Zr]DFO-YS5 demonstrated specific uptake in the PSMA and AR-negative DU145 model. [89Zr]DFO-YS5 also showed uptake in the patient-derived LTL-331 and 331R models, with particularly high uptake in the LTL-545 neuroendocrine prostate cancer tumors (18.8 ± 5.3, 12.5 ± 1.8, and 32.0 ± 5.3 % ID/g in LTL-331, LTL-331R, and LTL-545, respectively, at 4 days post injection).
[89Zr]DFO-YS5 is an excellent PET imaging agent across a panel of prostate cancer models, including in both adenocarcinoma and neuroendocrine prostate cancer, both cell line- and patient-derived xenografts, and both PSMA positive and negative tumors. It demonstrates potential for clinical translation as an imaging agent, theranostic platform, and companion biomarker in prostate cancer.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2020 Dec 08 [Epub ahead of print]
Sinan Wang, Jun Li, Jun Hua, Yang Su, Denis R Beckford Vera, Walter Zhao, Mayuri Jayaraman, Tony L Huynh, Ning Zhao, Yung-Hua Wang, Yangjie Huang, Fujun Qin, Sui Shen, Daniel Gioeli, Robert Dreicer, Renuka Sriram, Emily A Egusa, Jonathan Chou, Felix Y Feng, Rahul Aggarwal, Michael J Evans, Youngho Seo, Bin Liu, Robert R Flavell, Jiang He
Department of Radiology and Biomedical Imaging, University of California, San Francisco., Radiology and Medical imaging, University of Virginia., Department of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center., Radiology and Biomedical Imaging, University of California, San Francisco., Radiology, University of California, San Francisco., Pathology, University of Virginia., Radiation Oncology, University of Alabama at Birmingham., Microbiolgoy, Immunolgoy, and Cancer Biology, University of Virginia., Medicine, University of Virginia., Department of Radiation Oncology, University of California, San Francisco., Medicine, University of California, San Francisco., Radiation Oncology, Helen Diller Comprehensive Cancer Center, University of California, San Francisco., Department of Anesthesia, University of California, San Francisco., Radiology and Biomedical Imaging, and Pharmaceutical Chemistry, University of California, San Francisco .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/33293372