Dosimetry of fractionated administration of 125I-labeled antibody at experimental radioimmunotargeting.

Abstract

Radiotherapy of solid tumors is preferably performed in fractionated doses. Conversely, radioimmunotherapy with nuclide-carrying antibodies delivers a continuously decreasing low dose rate during a longer time period after a single injection. In the current study, the same total amount of 125I-labeled anticytokeratin monoclonal antibody (MoAb) was administrated in one, three, or ten injections and the dosimetry was evaluated. Three groups of nude mice (10 mice each) with HeLa Hep 2 xenografts were injected with 1 x 100 microg/22.2 megabecquerel (MBq), 3 x 33 microg/7.4 MBq, and 10 x 10 microg/2.22 MBq 125I-labeled TS1 MoAb, respectively. The mice were examined scintigraphically over a 54-day period (total number of radio immunoscintigraphies (RISs) = approximately 700) and doses to tumor and normal tissues were estimated according to the medical internal radiation dose formalism. A single bolus injection caused higher tumor uptake, tumor dose, and tumor to nontumor dose ratio than administration of the same total dose of antibody and radioactivity in three or ten separate injections. The single bolus injection caused a tenfold higher tumor uptake (% injected dose, or ID) compared with the group receiving ten injections. This caused a tumor dose of 17 gray to the group receiving a single bolus injection. In this antigen target system, a single injection of a large amount of antibody was found to be more efficient than the same antibody dose subdivided into three or ten fractions. It was concluded that not only the radioactivity but also the amount of antibody per fraction should be considered when determining optimal fractionated radioimmunotherapy.