Data from Molecular Imaging of Prostate Cancer Targeting CD46 Using ImmunoPET

Abstract

<div>AbstractPurpose:<p>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.</p>Experimental Design:<p>[<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<sup>+</sup>, prostate-specific membrane antigen–negative (PSMA<sup>−</sup>)] or 22Rv1 (AR<sup>+</sup>, CD46<sup>+</sup>, PSMA<sup>+</sup>) tumors, and in NOD/SCID gamma mice bearing patient-derived adenocarcinoma xenograft, LTL-331, and neuroendocrine prostate cancers, LTL-331R and LTL-545.</p>Results:<p>[<sup>89</sup>Zr]DFO-YS5 binds specifically to the CD46-positive human prostate cancer DU145 and 22Rv1 xenografts. In biodistribution studies, the tumor uptake of [<sup>89</sup>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, [<sup>89</sup>Zr]DFO-YS5 demonstrated specific uptake in the PSMA- and AR-negative DU145 model. [<sup>89</sup>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).</p>Conclusions:<p>[<sup>89</sup>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.</p></div>