Influence of DOTA chelators on radiochemical purity and biodistribution in xenografted mice of 177Lu- and 90Y-Rituximab

Introduction This work presents a comparative biological evaluation of 90Y- and 177Lu- labelled DOTA-SCN and DOTA-NHS conjugated to Rituximab in tumour-bearing mice. Materials and methods 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-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 PhotonIMAGERTM after injection of 90Y-DOTA(SCN)-Rituximab. Results and Conclusion 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 177Lu- and 90Y-DOTA(SCN)-Rituximab revealed slow blood clearance. The maximum tumour uptake was found 72 h after injection of 177Lu-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.