Pretargeting vs. direct targeting of human betalox5 islet cells subcutaneously implanted in mice using an anti-human islet cell antibody.
BACKGROUND
We previously demonstrated MORF/cMORF pretargeting of human islets and betalox 5 cells (a human beta cell line) transplanted subcutaneously in mice with the anti-human islet antibody, HPi1. We now compare pretargeting with direct targeting in the beta cell transplant model to evaluate the degree to which target/non-target (T/NT) ratios may be improved by pretargeting.


METHODS
Specific binding of an anti-human islet antibody HPi1 to the beta cells transplanted subcutaneously in mice was examined against a negative control antibody. We then compared pretargeting by MORF-HPi1 plus 111In-labeled cMORF to direct targeting by 111In-labeled HPi1.


RESULTS
HPi1 binding to betalox5 human cells in the transplant was shown by immunofluorescence. Normal organ 111In backgrounds by pretargeting were always lower, although target accumulations were similar. More importantly, the transplant to pancreas and liver ratios was, respectively, 26 and 10 by pretargeting as compared to 9 and 0.6 by direct targeting.


CONCLUSIONS
Pretargeting greatly improves the T/NT ratios, and based on the estimated endocrine to exocrine ratio within a pancreas, pretargeting may be approaching the sensitivity required for successful imaging of human islets within this organ.
Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA. guozheng.liu@umassmed.edu
Guozheng
G
Liu
Shuping
S
Dou
Ali
A
Akalin
Mary
M
Rusckowski
Philip R
PR
Streeter
Leonard D
LD
Shultz
Dale L
DL
Greiner
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D007205:Indium Radioisotopes; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D007553:Isotope Labeling; D051379:Mice; D060172:Morpholinos / Q000378:metabolism* / Q000493:pharmacokinetics; D012867:Skin
D000906:Antibodies; D007205:Indium Radioisotopes; D060172:Morpholinos