Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California.
Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, Virginia.
Clin Cancer Res. 2021 Mar 1;27(5):1305-1315. doi: 10.1158/1078-0432.CCR-20-3310. Epub 2020 Dec 8.
We recently identified CD46 as a novel therapeutic target in prostate cancer. In this study, we developed a CD46-targeted PET radiopharmaceutical, [Zr]DFO-YS5, and evaluated its performance for immunoPET imaging in murine prostate cancer models.
[Zr]DFO-YS5 was prepared and its 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.
[Zr]DFO-YS5 binds specifically to the CD46-positive human prostate cancer DU145 and 22Rv1 xenografts. In biodistribution studies, the tumor uptake of [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, [Zr]DFO-YS5 demonstrated specific uptake in the PSMA- and AR-negative DU145 model. [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).
[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.
我们最近发现 CD46 是前列腺癌的一个新的治疗靶点。在这项研究中，我们开发了一种针对 CD46 的 PET 放射性药物 [Zr]DFO-YS5，并评估了其在小鼠前列腺癌模型中的免疫 PET 成像性能。
制备 [Zr]DFO-YS5，并测量其与 CD46 的结合亲和力。在雄性无胸腺 nu/nu 小鼠中进行免疫 PET 成像，这些小鼠携带 DU145[AR、CD46、前列腺特异性膜抗原阴性（PSMA）]或 22Rv1（AR、CD46、PSMA）肿瘤，以及在 NOD/SCID gamma 小鼠中携带患者来源的腺癌异种移植瘤 LTL-331、神经内分泌前列腺癌 LTL-331R 和 LTL-545。
[Zr]DFO-YS5 特异性结合 CD46 阳性的人前列腺癌 DU145 和 22Rv1 异种移植瘤。在生物分布研究中，注射后 4 天，[Zr]DFO-YS5 在 DU145 和 22Rv1 异种移植瘤中的肿瘤摄取率分别为 13.3 ± 3.9%ID/g 和 11.2 ± 2.5%ID/g。值得注意的是，[Zr]DFO-YS5 在 PSMA 和 AR 阴性的 DU145 模型中显示出特异性摄取。[Zr]DFO-YS5 还在患者来源的 LTL-331 和 LTL-331R 模型中显示出摄取，其中 LTL-545 神经内分泌前列腺癌肿瘤的摄取率特别高（注射后 4 天，LTL-331、LTL-331R 和 LTL-545 中的摄取率分别为 18.8 ± 5.3%ID/g、12.5 ± 1.8%ID/g 和 32 ± 5.3%ID/g）。
[Zr]DFO-YS5 是一种出色的 PET 成像剂，可用于多种前列腺癌模型，包括腺癌和神经内分泌前列腺癌、细胞系和患者来源的异种移植瘤、PSMA 阳性和阴性肿瘤。它具有作为成像剂、治疗平台和前列腺癌伴随生物标志物在临床转化方面的潜力。
