Dosimetry of fractionated experimental radioimmunotargeting with idiotypic and anti-idiotypic anticytokeratin antibodies.

BACKGROUND

Repeated injections of iodine-125 (125I)-labeled tumor targeting anticytokeratin monoclonal antibody (TS1) and a nonlabeled antiidiotypic monoclonal antibody against TS1 (alphaTS1) were compared with a single injection of the radiolabeled TS1 in experimental radioimmunotargeting. 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 125I-labeled TS1. The animals in Group B received four injections of 125I-labeled TS1 (8-13 MBq) followed by alphaTS1 24 hours later, at 2-week intervals. The mean absorbed 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 order of magnitude was seen in Group B. An absolute increase in the tumor uptake was observed in Group B during the entire observation period. The mean absorbed dose to the tumors was 11 Gy at the end of the observation 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 confirmed an intensive heterogeneous accumulation of activity in the entire tumor.

CONCLUSIONS

The fractionated strategy can contribute to a significant accumulation of radiolabeled TS1 in the tumors. Furthermore, the use of alphaTS1 makes it possible to increase the tumor-to-nontumor dose ratio and maintain a prolonged high activity accumulation in the tumor.