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.
To find radioisotopic techniques based solutions to specific clinical needs of developing world in the area of cancer treatment, through the development and application of locally produced radiopharmaceuticals. (Project 2.5.1.3 (2008-9): Cost effective radiopharmaceuticals development.
To develop technologies for the evaluation and radiolabelling of conjugated monoclonal antibody (anti-CD20) using optimized method
To develop technologies for the production of conjugated monoclonal antibody (anti-CD20) using appropriate ligand
To develop technologies for the radiolabelling of 3 families of conjugated peptides
To develop the technologies for the production of peptide synthesis and conjugates
To develop unified methods for biological evaluation of radiolabelled monoclonal antibody (anti-CD20) using optimized protocol including animal studies and cell culture tests
To develop unified methods for biological evaluation of radiolabelled peptides using optimized protocol including animal studies and cell culture tests
To perform diagnostic and therapeutic studies in appropriate animal models bearing tumours as well as obtaining toxicity data
-The CRP has opened a new window for the preparation, QC and evaluation of monoclonal antibody-based radiopharmaceuticals in developing member states with limited funds.
-Initial positive arrangement has begun for creating a kit-level radiopharmaceutical by selected group pf institutes
-Interesting regional training course and meetings have been already planned as a consequence of this CRP in Asia and Latin America
This CRP focused on the development of an example RIT agents for the treatment of B-cell non-Hodgkin’s lymphomas, which are inherently radiosensitive and express antigens not typically found in normal tissue. Former murine antibodies were bond to CD20 (found on the surface of mature B cells and most B-cell malignancies) consisted of a linker-chelator tiuxetan to hold Yttrium-90, a beta-emitting radioisotope, for the purpose of RIT, however led to the development of human ant murine antibodies (HAMAs). A chimeric version of the antibody was produced — Rituximab — that exhibited a significant anti-lymphoma effect in the absence of the radioisotope and without the development of HAMAs which led to the FDA approval of Y-90-Ibritumomab tiuxetan in 2002 and I-131-Tositumomab in 2003. Both agents are indicated for relapsed or refractory low-grade B-cell non-Hodgkin lymphomas, while Y-90-Ibritumomab tiuxetan is also used in the frontline setting following at least a partial response to induction chemoimmunotherapy. Unfortunately both antibodies and the therapeutic procedure involved are highly expensive and are not widely available in many countries due to geographical, financial and other international limitations. RPRT section as a leading role player in the development and dissemination of radioisotope products and radiopharmaceuticals initiated this CRP in 2011.