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

This work presents a comparative biological evaluation of Y- and 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 (1). Tissue distribution was investigated in tumour-bearing (Raji s.c.) male Rj: NMRI-Foxn1/Foxn1 mice at different time points after administration of Lu-DOTA-Rituximab or Y-DOTA-Rituximab (6 MBq/10 μg per mouse). In addition, tumour images were acquired with a PhotonIMAGER after injection of Y-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- and Y-DOTA -(SCN)-Rituximab revealed slow blood clearance. The maximum tumour uptake was found 72 h after injection of 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.