Influence of DOTA Chelators on Radiochemical Purity and Biodistribution of <sup>177</sup>Lu- and <sup>90</sup>Y-Rituximab in Xenografted Mice
| Author | Urszula Karczmarczyk | en |
| Author | Wioletta Wojdowska | en |
| Author | Renata Mikołajczak | en |
| Author | Michał Maurin | en |
| Author | Ewa Laszuk | en |
| Author | Piotr Garnuszek | en |
| Issued Date | 2018-10-31 | en |
| Abstract | This work presents a comparative biological evaluation of 90Y- and 177Lu- 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-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. 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. | en |
| DOI | https://doi.org/10.22037/ijpr.2018.2298 | en |
| Keyword | Anti-CD20 | en |
| Keyword | <sup>177</sup>Lu and <sup>90</sup>Y | en |
| Keyword | Radiolabeling | en |
| Keyword | Rituximab | en |
| Keyword | DOTA chelator | en |
| Keyword | Animal study | en |
| Publisher | Brieflands | en |
| Title | Influence of DOTA Chelators on Radiochemical Purity and Biodistribution of <sup>177</sup>Lu- and <sup>90</sup>Y-Rituximab in Xenografted Mice | en |
| Type | Original Article | en |