Influence of DOTA Chelators on Radiochemical Purity and Bio distribution of 177^Lu- and 90^Y-Rituximab in Xeno grafted Mice

This work presents a comparative biological evaluation of 90^y- and 177^lu- labelled dota-scn and dota-nhs conjugated to rituximab in tumour-bearing mice. two dota derivatives, p-scn-bn-dota and dota-nhs-ester were conjugated to rituximab and then freeze-dried kit formulations were prepared, as previously described. tissue distribution was investigated in tumour-bearing (raji s.c.) male rj: nmri-foxn1nu/foxn1nu mice at different time points after administration of 177lu-dota-rituximab or 90y-dota-rituximab (6 mbq/10 µg per mouse). in addition, tumour images were acquired with a photon imagertm after injection of 90y-dota (scn)-rituximab. all radioimmun conjugates were obtained with high radiolabelling yield (rcp > 98%) and specific activity of ca. 0.6 gbq/mg. the conjugates were stable in human serum and in 0.9% nacl; however, progressive aggregation was observed with time, in particular for dota- (scn) conjugates. both 177^lu- and 90^y-dota-(scn)-rituximab revealed slow blood clearance. the maximum tumour uptake was found 72 h after injection of 177^lu-dota- (scn)-rituximab (9.3 id/g). a high radioactivity uptake was observed in liver and spleen, confirming the hepatobiliary excretion route. the results obtained by the radioactive optical imaging harmonize with those from the biodistribution study.