PHARMACOKINETICS AND BIODISTRIBUTION OF SAMARIUM-153-LABELED OC125 ANTIBODY COUPLED TO CITCDTPA IN A XENOGRAFT MODEL OF OVARIAN-CANCER

The use of samarium-153 in the context of radioimmunotherapy of cancer s has been limited by the instability of antibody labelling, which pro duces high uptake concentrations in liver and bone. This study compare s the pharmacokinetics and biodistribution of Sm-153-labelled OC125 mo noclonal antibody, in whole or F(ab')(2) fragment form and with diethy lene triamine penta-acetic acid (DTPA) or 6-p-isothiocyanatobenzyl die thylene triamine penta-acetic acid (CITCDTPA) coupling, in nude mice g rafted subcutaneously with an ovarian adenocarcinoma line (SHIN-3) exp ressing CA125 antigen. The specific activity of the immunoconjugates w as 18.5-55.5 MBq/mg, and their immunoreactivity exceeded 65%. With Sm- 153-DTPA-OC125F(ab')(2), the stability study in serum indicated that 5 0% of the metal remained bound to the antibody. The pharmacokinetic st udy showed a retention half-life of 25.1 h and blood clearance of 0.72 ml/h. The biodistribution study indicated tumour uptake of 4.53%+/-0. 49% of injected activity per gram (%ID/g) at 24 h and tumour-to-liver and tumour-to-bone ratios of 0.23+/-0.02 and 1.54+/-0.49 respectively at 24 h. With Sm-153-CITCDTPA-OC125F(ab')(2), serum stability was grea ter (87% of the metal remaining bound to the antibody), retention half -life was 22.25 h and blood clearance was 2.23 ml/h. Tumour was better targeted (8.30%+/-3.56%ID/g at 24 h), and tumour-to-liver and tumour- to-bone ratios were 1.17+/-0.36 and 7.08+/-3.09 respectively at 24 h. However, renal retention remained elevated (29.76%+/-9.41%ID/g at 24 h ). With intact IgG, renal uptake decreased (1.41%+/-0.49%ID/g at 24 h) , but tumour uptake was lower than with fragments (1.46%+/-0.58%ID/g a t 24 h). Liver uptake was higher (tumour-to-liver ratio 0.10+/-0.05), and blood clearance was slower. The stability and distribution of Sm-1 53-CITCDTPA were more favourable than those of Sm-153-DTPA for applica tion in radioimmunotherapy. Quantitative analysis performed using digi tized images obtained by conventional autoradiography and the imaging plate system indicated that the latter system is suitable for biodistr ibution studies of immunoconjugates.