DOSIMETRY OF FRACTIONATED EXPERIMENTAL RADIOIMMUNOTARGETING WITH IDIOTYPIC AND ANTIIDIOTYPIC ANTICYTOKERATIN ANTIBODIES

BACKGROUND, Repeated injections of iodine-125 (I-125)-labeled tumor ta rgeting anticytokeratin monoclonal antibody (TS1) and a nonlabeled ant iidiotypic monoclonal antibody against TS1 (alpha TS1) were compared w ith a single injection of the radiolabeled TS1 in experimental radioim munotargeting. Anti-TS1 was used to remove nontargeting TS1. METHODS, Nude mice were inoculated with HeLa Hep2 cells. The animals in Group A received a single injection of 13 MBq I-125-labeled TS1. The animals in Group B received four injections of I-125-labeled TS1 (8-13 MBq) fo llowed by alpha TS1 24 hours later, at 2-week intervals. The mean abso rbed doses were calculated according to the Medical Internal Radiation Dose Committee criteria based on repetitive radioimmunoscintigraphies during an observation period of 59 days. RESULTS, A 11 gray (Gy) mean dose to the tumor and 2 Gy to the whole body was achieved in Group A. Mean peak tumor uptake of 5% of the injected dose (ID), corresponding to 14 % ID/g, was observed on Day 17 after a single injection of the labeled monoclonal antibody. A mean peak tumor uptake of the same orde r of magnitude was seen in Group B. An absolute increase in the tumor uptake was observed in Group B during the entire observation period. T he mean absorbed dose to the tumors was 11 Gy at the end of the observ ation period, whereas the whole body dose was only 2.5 Gy in Group B. Autoradiography of the tumors at the end of the observation period con firmed an intensive heterogeneous accumulation of activity in the enti re tumor. CONCLUSIONS. The fractionated strategy can contribute to a s ignificant accumulation of radiolabeled TS1 in the tumors. Furthermore , the use of alpha TS1 makes it possible to increase the tumor-to-nont umor dose ratio and maintain a prolonged high activity accumulation in the tumor. (C) 1997 American Cancer Society.