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Title: Alpha particle radioimmunotherapy: Animal models and clinical prospects

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 {sup 212}Bi-anti-Thy 1.2 immunoconjugates are capable of extraordinary cytotoxicity in vitro, requiring approximately three {sup 212}Bi-labeled conjugates per target cell to suppress {sup 3}H-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 microCi per mouse. Alpha particle emitting radioimmunoconjugates show great potential for regional and intracavitary molecular radiotherapy.
Authors:
; ; ; ; ; ;  [1]
  1. (Dana Farber Cancer Institute, Boston, MA (USA))
Publication Date:
OSTI Identifier:
5561418
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; (USA); Journal Volume: 16:6
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; NEOPLASMS; RADIOIMMUNOTHERAPY; ALPHA PARTICLES; ANTIGENS; BIOLOGICAL MODELS; BISMUTH 212; EXPERIMENTAL NEOPLASMS; IN VITRO; MICE; MONOCLONAL ANTIBODIES; THYMIDINE; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ALPHA DECAY RADIOISOTOPES; ANIMALS; ANTIBODIES; AZINES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BISMUTH ISOTOPES; CHARGED PARTICLES; DISEASES; HEAVY NUCLEI; HETEROCYCLIC COMPOUNDS; HOURS LIVING RADIOISOTOPES; HYDROGEN COMPOUNDS; IMMUNOLOGY; IMMUNOTHERAPY; ISOTOPE APPLICATIONS; ISOTOPES; MAMMALS; MEDICINE; NUCLEAR MEDICINE; NUCLEI; NUCLEOSIDES; NUCLEOTIDES; ODD-ODD NUCLEI; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PYRIMIDINES; RADIOIMMUNOLOGY; RADIOISOTOPES; RADIOLOGY; RADIOTHERAPY; RIBOSIDES; RODENTS; THERAPY; VERTEBRATES 550604* -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)