Development and Preclinical Evaluations of Therapeutic Radiopharmaceuticals Based on Lu-177 and Y-90 Labeled Monoclonal Antibodies and Peptides

Targeted radionuclide therapy (RNT) with labelled monoclonal antibodies (mAbs) and peptides has emerged as a complementary modality for the treatment of certain cancers. Several mAbs have been investigated and some introduced for immunotherapy of various cancers. Two radiolabeled mAbs,  Zevalin® (labelled with 90Y) and Bexxar® (labelled with 131I), have been approved for radioimmunotherapy (RIT) of B-cell lymphomas. The IAEA has been supporting the development of widely usable products for RNT, in particular those based on yttrium-90 and lutetium-177. The present CRP aims at providing technology needed to prepare 177Lu or 90Y labelled mAbs and peptides for the treatment of primary cancers. Specifically, the CRP is focused on the development of an easy-to-make kit formulation for the preparation of 177Lu- or 90Y- DOTA-Rituximab for RIT studies in patients with B-cell lymphomas. Similarly, the CRP will also pursue developing an easy-to-make kit formulation for the labelling of substance P (SP), a peptide targeting NK-1 receptors, with 177Lu and 90Y and evaluate it as a therapeutic agent for intracavity treatment of glioblastoma. Preclinical studies on isolated cells and animal models will be also undertaken to assess the pharmacokinetic profile of 177Lu/90Y- DOTA-Rituximab and 177Lu/90Y-DOTA-SP. It is expected that these data, combined with the availability of the corresponding kit formulations, will largely assist and accelerate the subsequent clinical investigation in humans of these new therapeutic radiopharmaceuticals.