188Re-direct labeling of monoclonal antibodies for radioimmunotherapy of solid tumors: biodistribution, normal organ dosimetry, and toxicology.
The increased interest in the availability of radionuclides for therapy has resulted from the recent success and potential importance of radiolabeled antibodies for both diagnosis and therapy. There is a widespread interest in the availability of 188Re for various therapeutic applications, particularly for attachment to tumor-specific monoclonal antibodies for radioimmunotherapy. This review provides a perspective of 188Re-direct labeled MAbs for radioimmunotherapy of solid tumors, normal organ biodistribution, absorbed radiation doses to normal organs and tumors, and the toxicity to bone marrow and normal tissues. Methods for calculation of mean absorbed radiation doses to the whole body, various normal organs, and tumors have been developed using source-organ residence times and the methods developed by the Medical Internal Radiation Dose (MIRD) committee. The toxicity for 188Re-labeled antibodies is predominantly hematopoietic, with platelets and white blood cells being most sensitive to the effects of radiation. Rhenium-188 would be the isotope of choice for radioimmunotherapeutic applications because of cost, availability, and favorable radiation characteristics. Rhenium-188 has a half-life of 16.9 h and maximum beta energy of 2.118 MeV. This isotope is particularly attractive because it can be supplied conveniently from 188W/188Re-radionuclide generator system.
Center of Molecular Immunology, Havana, Cuba. normando@ict.cim.sld.cu
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Iznaga-Escobar
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D007553:Isotope Labeling; D009369:Neoplasms / Q000628:therapy*; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes; D011874:Radiometry; D012211:Rhenium; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D012211:Rhenium