Radiolabeled nano‐peptides show specificity for an animal model of human PC3 prostate cancer cells

OBJECTIVES: Cancer has been investigated using various pre‐targeting techniques or models focusing on radiobombesin analogues; however, both are not offered together. In this study, nano‐bombesin labeling by a pre‐targeting system was undertaken to develop an alternative approach for prostate tumor treatment. METHODS: A two‐step pre‐targeting system utilizing a combination of streptavidin (SA), biotinylated morpholino (B‐MORF), biotinylated BBN (B‐BBN) with two different spacers (β‐Ala and PEG), and a radiolabeled cMORF was evaluated in vitro and in vivo. RESULTS: Final conjugation conditions consisted of a 1:1:2 ratio of SA:B‐MORF:B‐BBN, followed by addition of (99m)Tc‐cMORF to compensate for free MORF. In vitro binding experiments with prostate cancer cells (PC‐3) revealed that total binding was time‐dependent for the Ala spacer but not for the PEG spacer. The highest accumulation (5.06±1.98 %) was achieved with 1 hour of incubation, decreasing as time progressed. Specific binding fell to 1.05±0.35 %. The pre‐targeting biodistribution in healthy Swiss mice was measured at different time points, with the best responses observed for 7‐h and 15‐h incubations. The effector, (99m)Tc‐MAG3‐cMORF, was administered 2 h later. Strong kidney excretion was always documented. The greatest tumor uptake was 2.58±0.59 %ID/g at 7 h for B‐βAla‐BBN, with a region of interest (ROI) value of 3.9 % during imaging. The tumor/blood ratio was low due to the slow blood clearance; however, the tumor/muscle ratio was 5.95. CONCLUSIONS: The pre‐targeting approach with a peptide was a viable concept. Further evaluation with modified sequences of MORF, including less cytosine, and additional test intervals could be worthwhile.