Tumor pretargeting in mice using MORF conjugated CC49 antibody and radiolabeled complimentary cMORF effector

We previously reported high CD46 expression in prostate cancer and developed an antibody-drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. We hereby present the preclinical evaluation of a pretargeting imaging system based on the clinical stage YS5 antibody and phosphorodiamidate morpholino oligomers (MORF). Based on the UV absorbance analysis in our prior report, the YS5-MORF conjugates were determined to be about 1.6 to 1.8 MORF molecules per antibody. In animals, 64Cu-MORF cleared fast through kidney excretion and accumulated in tumors. The tumor uptake is the highest at both time points at 3h and 18h post-injection of 64Cu-MORF injection. Tumor uptake in the study group (4.2%ID/g) is about 7-fold of that in the control group (0.6%ID/g) at 3h pi while it is about 10 folds at 3.4%ID/g vs 0.3%ID/g for 18h post-injection. PET imaging detected the tumor at high contrast with less uptake in kidneys (<3%ID/g) and minimal uptake in other organs (<0.5%ID/g).