Pharmacokinetics and biodistribution of samarium-153-labelled OC125 antibody coupled to CITCDTPA in a xenograft model of ovarian cancer

The use of samarium-153 in the context of radioimmunotherapy of cancers has been limited by the instability of antibody labelling, which produces high uptake concentrations in liver and bone. This study compares the pharmacokinetics and biodistribution of¹⁵³Sm-labelled OC125 monoclonal antibody, in whole or F(ab)₂ fragment form and with diethylene triamine penta-acetic acid (DTPA) or 6-p-isothiocyanatobenzyl diethylene triamine penta-acetic acid (CITCDTPA) coupling, in nude mice grafted subcutaneously with an ovarian adenocarcinoma line (SHIN-3) expressing CA125 antigen. The specific activity of the immunoconjugates was 18.5–55.5 MBq/mg, and their immunoreactivity exceeded 65%. With¹⁵³Sm-DTPA-OC125F(ab)₂, the stability study in serum indicated that 50% of the metal remained bound to the antibody. The pharmacokinetic study 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%±9% 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. With¹⁵³Sm-CITCDTPA-OC125F(ab)₂, serum stability was greater (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 at 24 h). Liver uptake was higher (tumour-to-liver ratio 0.10±0.05), and blood clearance was slower. The stability and distribution of¹⁵³Sm-CITCDTPA were more favourable than those of¹⁵³Sm-DTPA for application in radioimmunotherapy. Quantitative analysis performed using digitized images obtained by conventional autoradiography and the imaging plate system indicated that the latter system is suitable for bio-distribution studies of immunoconjugates.