Influence of DOTA Chelators on Radiochemical Purity and Biodistribution of 177Lu- and 90Y-Rituximab in Xenografted Mice

This work presents a comparative biological evaluation of Y-90- and Lu-177- 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 (1). Tissue distribution was investigated in tumour-bearing (Raji s.c.) male Rj: NMRI-Foxn1(nu)/Foxn1(nu) mice at different time points after administration of Lu-177-DOTA Rituximab or Y-90-DOTA-Rituximab (6 MBq/10 mu g per mouse). In addition, tumour images were acquired with a PhotonIMAGER (TM) after injection of Y-90-DOTA (SCN)-Rituximab. All radioimmunoconjugates 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 Lu-177- and Y-90-DOTA-(SCN)-Rituximab revealed slow blood clearance. The maximum tumour uptake was found 72 h after injection of (177)Thu-DOTA- (SCN)-Rituximab (9.3 ID/g). A high radioactivity uptake was observed in liver and spleen, confirming the hepatobiliaiy excretion mute. The results obtained by the radioactive optical imaging harmonize with those from the biodistribution study.