Dataset Information

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.

SUBMITTER: Wang S

PROVIDER: S-EPMC7925362 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Molecular Imaging of Prostate Cancer Targeting CD46 Using ImmunoPET.

Wang Sinan S Li Jun J Hua Jun J Su Yang Y Beckford-Vera Denis R DR Zhao Walter W Jayaraman Mayuri M Huynh Tony L TL Zhao Ning N Wang Yung-Hua YH Huang Yangjie Y Qin Fujun F Shen Sui S Gioeli Daniel D Dreicer Robert R Sriram Renuka R Egusa Emily A EA Chou Jonathan J Feng Felix Y FY Aggarwal Rahul R Evans Michael J MJ Seo Youngho Y Liu Bin B Flavell Robert R RR He Jiang J

Clinical cancer research : an official journal of the American Association for Cancer Research 20201208 5

<h4>Purpose</h4>We recently identified CD46 as a novel therapeutic target in prostate cancer. In this study, we developed a CD46-targeted PET radiopharmaceutical, [<sup>89</sup>Zr]DFO-YS5, and evaluated its performance for immunoPET imaging in murine prostate cancer models.<h4>Experimental design</h4>[<sup>89</sup>Zr]DFO-YS5 was prepared and its <i>in vitro</i> binding affinity for CD46 was measured. ImmunoPET imaging was conducted in male athymic nu/nu mice bearing DU145 [AR<sup>-</sup>, CD46<s ...[more]

PMID: 33293372

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Dataset Information

Molecular Imaging of Prostate Cancer Targeting CD46 Using ImmunoPET.

Purpose

Experimental design

Results

Conclusions

Publications

Molecular Imaging of Prostate Cancer Targeting CD46 Using ImmunoPET.

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