Resident's essay award: Alpha particle radio-immunotherapy: Animal models and clinical prospects

Roger M. Macklis, William D. Kaplan, James L.M. Ferrara, Robert W. Atcher, John J. Hines, Steven J. Burakoff, C. Norman Coleman

Research output: Contribution to journalArticlepeer-review

Abstract

Short-lived isotopes that emit alpha particles have a number of physical characteristics which make them attractive candidates for radioimmunotherapy. Among these characteristics are high linear energy transfer and correspondingly high cytotoxicity; particle range limited to several cell diameters from the parent atom; low potential for repair of alpha-induced DNA damage; and low dependence on dose rate and oxygen enhancement effects. This report reviews the synthesis, testing and use in animal models of an alpha particle emitting radioimmunoconjugate constructed via the noncovalent chelation of Bismuth-212 to a monoclonal IgM antibody specific for the murine T cells/ neuroectodermal surface antigen, Thy 1.2. These 212Bi-anti-Thy 1.2 immunoconjugates are capable of extraordinary cytotoxicity in vitro, requiring approximately three 212Bi-labeled conjugates per target cell to suppress 3H-thymidine incorporation to background levels. The antigen specificity afforded by the monoclonal antibody contributes a factor of approximately 40 to the radiotoxicity of the immunoconjugate. Animals inoculated with a Thy 1.2+ malignant ascites were cured of their tumor in an antigen-specific fashion by intraperitoneal doses of approximately 200 μCi per mouse. Alpha particle emitting radioimmunoconjugates show great potential for regional and intracavitary molecular radiotherapy.

Original languageEnglish (US)
Pages (from-to)1377-1387
Number of pages11
JournalInternational journal of radiation oncology, biology, physics
Volume16
Issue number6
DOIs
StatePublished - Jun 1989

Keywords

  • Alpha particle radio-immunotherapy
  • Animal models
  • Bi-212
  • Immunoconjugates
  • Molecular radiotherapy

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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