Clinical aspects and future advances of targeted alpha therapy in oncology

This educational presentation will give an overview about the clinical application of targeted alpha therapy (TAT) introduced until now. From Bi-213 tagged antibodies in patients with lymphoma and leukemia to the clinical evaluation in malignant melanoma and more recently the applications of chelateable alpha-nuclides to label peptide analogs of somatostatin in neuroendocrine tumors or substance P in brain tumors. The most advanced clinical application is currently achieved for the treatment with the bone seeker Ra-223 (Alpharadin). Most of the radiopharmaceuticals used for TAT are counterparts of established beta-therapies. We will discuss possible pros and cons of TAT in direct comparison to their corresponding beta-compounds. The limited availability of alpha-nuclides has prevented proliferation of TAT into clinical routine for a long time. In the meantime a cyclotron based production of Ac-225 has been developed and more experience with clinical Ac-225/Bi-213 generators is available. The production of Ac-227/Ra-223 generators by neutron irradiation of Ra-226 in a reactor is widely scalable. Therefore these alpha-emitting nuclides might be producible in unlimited amounts, once their clinical benefit has been proven. We will discuss perspectives for the implementation of these nuclides/generators into clinical routine. Ac-225 and Ra-223 decay in a sequence of four alpha disintegrations. We will discuss the relevance of translocation of the intermediate decay products and possible co-medication to avoid their accumulation in liver and kidneys. Still challenging for the future proliferation of alpha based therapies is the limitation of providing micro-dosimetry with diagnostic surrogates in SPECT and PET. Eventually alpha-radiopharmaceuticals must be evaluated more similar to chemotherapeutics than the classical dose estimation established for the radiation planning with beta emitters. Educational Objectives: 1. To give an overview about the clinical application of targeted alpha therapy introduced until now and how these treatments do compete in comparison to their corresponding beta-compounds, respectively. 2. Learning about the specific challenge in dosimetry and therefore dose-finding for radionuclides with insufficient emission of gamma radiation / bremsstrahlung and in regard to the heterogeneous dose distribution due to the short particle range. Implications for planning future studies. 3. (Short) review of generator systems suitable for clinical routine. 4. Possible co-medication to control the radioactive decay products of some alpha-nuclides.

KRATOCHWIL Clemens;  GIESEL Frederik;  MORGENSTERN Alfred; 

2013-01-14

SPRINGER

JRC71712

1619-7070,   

http://link.springer.com/journal/259/39/2/suppl/page/1#page-1,    https://publications.jrc.ec.europa.eu/repository/handle/JRC71712,   

10.1007/s00259-012-2220-y,