Intratumoral distribution and pharmacokinetics of the radiolabeled ICAM-1 targeting monoclonal antibody R6.5 in a...

Despite new therapies, castration-resistant prostate cancer (CRPC) is still incurable. Intercellular Adhesion Molecule 1 (ICAM-1) is a well-characterized cell surface protein involved in prostate cancer pathogenesis, differentially expressed during transition from hormone-sensitive to CRPC. This study aimed to investigate ICAM-1 as a target for imaging and radioimmunotherapy of CRPC.Anti-ICAM-1 antibody R6.5 was labeled with ¹¹¹In or ¹⁷⁷Lu, and a non-specific antibody with ¹⁷⁷Lu. In vitro uptake of R6.5 was tested in PC-3 prostate cancer cells. Biodistribution studies, SPECT/CT imaging, and autoradiography were performed in a PC-3 xenograft model.In vitro uptake of R6.5 ([¹⁷⁷Lu]Lu-R6.5) increased during 6 h of incubation. The uptake was higher at lower mAb concentration and could be blocked by 500 nM of unlabeled R6.5. In vivo and ex vivo biodistribution showed that [¹¹¹In]In-R6.5 and [¹⁷⁷Lu]Lu-R6.5 targeted the xenograft tumors better than the control Ab, however [¹¹¹In]In-R6.5 had better tumor uptake than [¹⁷⁷Lu]Lu-R6.5, probably due to less aggressive conjugation with chelator and smaller tumor sizes. From 24 h post-injection, the tumors in mice injected with [¹¹¹In]In-R6.5 and [¹⁷⁷Lu]Lu-R6.5 were visible on SPECT, optimal contrast at 48 h. Uptake was low in normal organs except the spleen and liver for all mAbs. Autoradiography showed [¹¹¹In]In-R6.5 and [¹⁷⁷Lu]Lu-R6.5 accumulated along the edges of viable tumor. The control Ab tended to accumulate in partly necrotic areas.This study demonstrates ICAM-1 as a potential target for theragnostics in CRPC.