Cancer radioimmunotherapy with alpha-emitting nuclides

Eur J Nucl Med Mol Imaging. 2005 May;32(5):601-14. doi: 10.1007/s00259-005-1803-2.

Abstract

In lymphoid malignancies and in certain solid cancers such as medullary thyroid carcinoma, somewhat mixed success has been achieved when applying radioimmunotherapy (RIT) with beta-emitters for the treatment of refractory cases. The development of novel RIT with alpha-emitters has created new opportunities and theoretical advantages due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha-particles. These physical properties offer the prospect of achieving selective tumoural cell killing. Thus, RIT with alpha-emitters appears particularly suited for the elimination of circulating single cells or cell clusters or for the treatment of micrometastases at an early stage. However, to avoid non-specific irradiation of healthy tissues, it is necessary to identify accessible tumoural targets easily and rapidly. For this purpose, a small number of alpha-emitters have been investigated, among which only a few have been used for in vivo preclinical studies. Another problem is the availability and cost of these radionuclides; for instance, the low cost and the development of a reliable actinium-225/bismuth-213 generator were probably determining elements in the choice of bismuth-213 in the only human trial of RIT with an alpha-emitter. This article reviews the literature concerning monoclonal antibodies radiolabelled with alpha-emitters that have been developed for possible RIT in cancer patients. The principal radio-immunoconjugates are considered, starting with physical and chemical properties of alpha-emitters, their mode of production, the possibilities and difficulties of labelling, in vitro studies and finally, when available, in vivo preclinical and clinical studies.

Publication types

  • Review

MeSH terms

  • Alpha Particles / therapeutic use*
  • Animals
  • Clinical Trials as Topic
  • Humans
  • Neoplasms / radiotherapy*
  • Radioimmunotherapy / methods*
  • Radioimmunotherapy / trends*
  • Radioisotopes / therapeutic use*
  • Radiopharmaceuticals / therapeutic use

Substances

  • Radioisotopes
  • Radiopharmaceuticals