In vivo evaluation of the radiolabeled ICAM-1 monoclonal antibody R6.5 in a prostate cancer mouse model

Objectives Intercellular Adhesion Molecule 1 (ICAM-1) is a protein localized on the surface of tumor cells and in tumor microenvironment, with an increased expression in castration resistant prostate cancer (CRPC) compared to hormone sensitive tumor cells. The purpose of this study was to evaluate ICAM-1 as a potential target for imaging prostate cancer (PCa) using the radiolabeled R6.5 monoclonal antibody (mAb).

Methods The IgG2 mAb R6.5 (Enlimomab, ATCC® HB-9580™) was conjugated with CHX-A''-DTPA and labeled with 111In or 177Lu. A mouse IgG2 antibody labeled with 177Lu was used as a control. Biodistribution, micro-SPECT/CT and digital autoradiography (DARG) studies were performed in nude mice bearing PC-3 human PCa subcutaneous xenografts after administration of radiolabeled R6.5. For comparison, PET imaging and multi-isotope DARG studies were also performed with simultaneous 18FDG or 18F-choline in the same animals.

Results Biodistribution data showed that 111In-R6.5 had better uptake and favorable biokinetics than 177Lu-R6.5 and 177Lu-IgG2 antibodies. SPECT/CT images corresponded with ex vivo biodistribution data, showing specific uptake of R6.5 in the tumors 24 hours post injection (hpi) and improved image contrast at 48 hpi. The 18FDG PET/CT images compared best to the SPECT/CT images of the same animals. DARG showed labeled-R6.5 accumulated in areas along the edges of viable tumor and where viable cells were less densely packed.

Conclusions This study demonstrated with ex vivo and in vivo biodistribution studies using the radiolabeled antibody R6.5, that ICAM-1 is a potential target for imaging PCa. ICAM-1 is a promising target to monitor aggressive forms of PCa including metastases and tumor microenvironment.

Research Support Swedish Cancer Foundation, Swedish Research Council, Mrs. Bertha Kamprad Foundation, Gunnar Nilsson Cancer Foundation Medicine (VR), Medical Faculty ALF grant, Lund University and the Eurostars program through the Swedish Governmental Agency for Innovation Systems (VINNOVA).