Molecular Imaging of Prostate Cancer Targeting CD46 Using ImmunoPET.

Autor:	Wang S; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Li J; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia.; Department of Nuclear Medicine, Huashan Hospital, Fudan University, Shanghai, P.R. China., Hua J; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia.; Department of Nuclear Medicine, Chongqing University Cancer Hospital, Chongqing, P.R. China., Su Y; Department of Anesthesia, University of California, San Francisco, San Francisco, California., Beckford-Vera DR; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Zhao W; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Jayaraman M; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Huynh TL; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Zhao N; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Wang YH; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Huang Y; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Qin F; Department of Pathology, University of Virginia, Charlottesville, Virginia., Shen S; Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama., Gioeli D; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia.; University of Virginia Cancer Center, Charlottesville, Virginia., Dreicer R; University of Virginia Cancer Center, Charlottesville, Virginia.; Departments of Medicine and Urology, University of Virginia, Charlottesville, Virginia., Sriram R; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California., Egusa EA; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.; Department of Radiation Oncology, University of California, San Francisco, San Francisco, California., Chou J; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.; Department of Radiation Oncology, University of California, San Francisco, San Francisco, California., Feng FY; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.; Department of Radiation Oncology, University of California, San Francisco, San Francisco, California., Aggarwal R; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.; Division of Hematology and Oncology, University of California, San Francisco, San Francisco, California., Evans MJ; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California.; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California., Seo Y; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California.; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.; Department of Radiation Oncology, University of California, San Francisco, San Francisco, California., Liu B; Department of Anesthesia, University of California, San Francisco, San Francisco, California. Robert.Flavell@ucsf.edu bin.liu@ucsf.edu jh6qv@virginia.edu.; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California., Flavell RR; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California. Robert.Flavell@ucsf.edu bin.liu@ucsf.edu jh6qv@virginia.edu.; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California., He J; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia. Robert.Flavell@ucsf.edu bin.liu@ucsf.edu jh6qv@virginia.edu.; University of Virginia Cancer Center, Charlottesville, Virginia.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Mar 01; Vol. 27 (5), pp. 1305-1315. Date of Electronic Publication: 2020 Dec 08.
DOI:	10.1158/1078-0432.CCR-20-3310
Abstrakt:	Purpose: We recently identified CD46 as a novel therapeutic target in prostate cancer. In this study, we developed a CD46-targeted PET radiopharmaceutical, [ 89 Zr]DFO-YS5, and evaluated its performance for immunoPET imaging in murine prostate cancer models. Experimental Design: [ 89 Zr]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: [ 89 Zr]DFO-YS5 binds specifically to the CD46-positive human prostate cancer DU145 and 22Rv1 xenografts. In biodistribution studies, the tumor uptake of [ 89 Zr]DFO-YS5 was 13.3 ± 3.9 and 11.2 ± 2.5 %ID/g, respectively, in DU145 and 22Rv1 xenografts, 4 days postinjection. Notably, [ 89 Zr]DFO-YS5 demonstrated specific uptake in the PSMA- and AR-negative DU145 model. [ 89 Zr]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: [ 89 Zr]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. (©2020 American Association for Cancer Research.)
Databáze:	MEDLINE
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