Pretargeting vs direct targeting of human betalox5 islet cells subcutaneously implanted in mice using an anti-human islet cell antibody

Introduction Our previous investigation showed the proof-of-concept of islet cell and islet imaging by pretargeting, however, it is important to know whether the pretargeting strategy was really playing a key role. The improvement by pretargeting over direct targeting is now evaluated in terms of target accumulations and target/non-target (T/NT) ratios. Methods Specific binding of an anti-human islet antibody HPi1 to betalox5 human beta cells transplanted subcutaneously in mice was examined against a negative antibody control. Pretargeting by MORF-HPi1 plus 111In-labeled cMORF was then compared to direct targeting by 111In-labeled HPi1. Results HPi1 binding to betalox5 human cells in the transplant was visualized directly by immunofluorescence. Normal organ 111In backgrounds by pretargeting were always lower, although target accumulations were similar. The transplant to pancreas and liver ratios were respectively 26 and 10 by pretargeting as compared to 9 and 0.6 by direct targeting. Conclusions Pretargeting greatly improves T/NT ratios and, based on the estimated endocrine to exocrine ratio within a pancreas, pretargeting may be approaching the sensitivity required for successful targeting of human islets within a pancreas