Quantitative Immuno-SPECT Monitoring of Pretargeted Radioimmunotherapy with a Bispecific Antibody in an Intraperitoneal Nude Mouse Model of Human Colon Cancer

Abstract

The prospects for using pretargeted immuno-SPECT to monitor the response to pretargeted radioimmunotherapy were examined. In this study, a bispecific anticarcinoembryonic antigen (CEACAM5; CD66e) × antihapten monoclonal antibody, TF2, was used in combination with a small (1.5 kD) peptide, IMP288, labeled with (111)In and (177)Lu. First, tumor uptake of (111)In-IMP288 and (177)Lu-IMP288, as determined by immuno-SPECT, was validated by ex vivo counting. Two groups of female BALB/c nude mice had LS174T tumors implanted in the peritoneal cavity. They received intravenous injections of TF2, followed by 10 MBq of (111)In-IMP288 or 90 MBq of (177)Lu-IMP288. A control group of non-tumor-bearing mice received TF2 and (111)In-IMP288. One hour after the radiolabeled IMP288 was given, small-animal SPECT/CT images were acquired, and subsequently animals were dissected. Furthermore, a survival study was performed in 3 groups of 10 mice with intraperitoneal tumors: mice received TF2 and (177)Lu-IMP288 (60 MBq), nonpretargeted (177)Lu-IMP288 (60 MBq), or phosphate-buffered saline. Immuno-SPECT scans were acquired directly after therapy and at 14 and 45 d after therapy. Tumor growth was analyzed in the successive scans in each animal. (111)In- and (177)Lu-labeled IMP288 had similar in vivo distribution. The activity measured in the pretargeted immuno-SPECT images correlated well with the uptake measured in the dissected tumors (Pearson r = 0.99, P < 0.05). In the therapy study, the SPECT images showed rapid and selective tumor targeting with high tumor-to-background contrast (30 ± 12) as early as 1 h after injection. The successive images of the treated mice showed delayed tumor growth in the pretargeted radioimmunotherapy group, corresponding with their prolonged survival. Pretargeted immuno-SPECT with TF2 and (111)In- or (177)Lu-IMP288 can be used to predict and confirm tumor targeting and monitor the therapeutic effect of pretargeted radioimmunotherapy.