Alpha particle radioimmunotherapy: Animal models and clinical prospects

Journal Article · Thu Jun 01 04:00:00 EDT 1989 · International Journal of Radiation Oncology, Biology and Physics; (USA)

DOI:https://doi.org/10.1016/0360-3016(89)90938-3· OSTI ID:5561418

Macklis, R M; Kaplan, W D; Ferrara, J L; Atcher, R W; Hines, J J; Burakoff, S J; Coleman, C N ^[1]

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1. Dana Farber Cancer Institute, Boston, MA (USA)

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.

• OSTI ID: 5561418
• Journal Information: International Journal of Radiation Oncology, Biology and Physics; (USA), Journal Name: International Journal of Radiation Oncology, Biology and Physics; (USA) Vol. 16:6; ISSN IOBPD; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

550604* -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ALPHA DECAY RADIOISOTOPES
ALPHA PARTICLES
ANIMALS
ANTIBODIES
ANTIGENS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MODELS
BISMUTH 212
BISMUTH ISOTOPES
CHARGED PARTICLES
DISEASES
EXPERIMENTAL NEOPLASMS
HEAVY NUCLEI
HETEROCYCLIC COMPOUNDS
HOURS LIVING RADIOISOTOPES
HYDROGEN COMPOUNDS
IMMUNOLOGY
IMMUNOTHERAPY
IN VITRO
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MEDICINE
MICE
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEAR MEDICINE
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIMIDINES
RADIOIMMUNOLOGY
RADIOIMMUNOTHERAPY
RADIOISOTOPES
RADIOLOGY
RADIOTHERAPY
RIBOSIDES
RODENTS
THERAPY
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES