Molecular Imaging of Prostate Cancer Targeting CD46 Using ImmunoPET.

Abstract

PURPOSE:

We recently identified CD46 as a novel therapeutic target in prostate cancer. In this study, we developed a CD46-targeted PET radiopharmaceutical, [89Zr]DFO-YS5, and evaluated its performance for immunoPET imaging in murine prostate cancer models.

EXPERIMENTAL DESIGN:

[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+, prostate-specific membrane antigen-negative (PSMA-)] or 22Rv1 (AR+, CD46+, PSMA+) tumors, and in NOD/SCID gamma mice bearing patient-derived adenocarcinoma xenograft, LTL-331, and neuroendocrine prostate cancers, LTL-331R and LTL-545.

RESULTS:

[89Zr]DFO-YS5 binds specifically to the CD46-positive human prostate cancer DU145 and 22Rv1 xenografts. In biodistribution studies, the tumor uptake of [89Zr]DFO-YS5 was 13.3 ± 3.9 and 11.2 ± 2.5 %ID/g, respectively, in DU145 and 22Rv1 xenografts, 4 days postinjection. 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 ± 5.3 %ID/g in LTL-331, LTL-331R, and LTL-545, respectively, at 4 days postinjection).

CONCLUSIONS:

[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.

• Authors: 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
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 27 Issue 5 Pg. 1305-1315 (03 01 2021) ISSN: 1557-3265 [Electronic] United States
• PMID: 33293372 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• CD46 protein, human
• Immunoconjugates
• Membrane Cofactor Protein
• Radiopharmaceuticals
• Zirconium

Topics

• Adenocarcinoma (diagnostic imaging, immunology, metabolism, pathology)
• Animals
• Apoptosis
• Cell Proliferation
• Humans
• Immunoconjugates (chemistry)
• Male
• Membrane Cofactor Protein (immunology)
• Mice
• Mice, Inbred NOD
• Mice, Nude
• Mice, SCID
• Molecular Imaging (methods)
• Neuroendocrine Tumors (diagnostic imaging, immunology, metabolism, pathology)
• Positron-Emission Tomography (methods)
• Prostatic Neoplasms (diagnostic imaging, immunology, metabolism, pathology)
• Radiopharmaceuticals (pharmacokinetics)
• Tissue Distribution
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays
• Zirconium (chemistry)