Howell R W, Goddu S M, Rao D V
Department of Radiology, University of Medicine & Dentistry of New Jersey, New Jersey Medical School, Newark 07103.
J Nucl Med. 1994 Nov;35(11):1861-9.
Radioimmunotherapy (RIT), as it is currently practiced, delivers low doses to tumors primarily because of dose-limiting bone marrow toxicity. The biologic effectiveness of RIT depends on the total dose, dose rate and the fractionation schedule of the radiolabeled antibodies administered.
An approach based on the linear-quadratic (LQ) model, which is currently used in conventional radiotherapy, is advanced for treatment planning in RIT. This approach incorporates repair rates, radiosensitivity of the tissues, biologic half-lives of the antibodies, physical half-lives of the radionuclides, dose rates and total doses needed for a given biologically effective dose. The concept of a relative advantage factor (RAF) is introduced to quantify the therapeutic gain that can be realized by using longer-lived radionuclides instead of the shorter-lived counterparts currently in use.
RAFs are calculated for different biologic and physical half-lives, and values as high as 3 to 5 can be attained when longer-lived radionuclides are used. The RAFs predicted by the LQ model reaffirm the authors' earlier conclusion based on the time-dose-fractionation approach that relatively long-lived radionuclides coupled to monoclonal antibodies are indeed more likely to deliver therapeutically effective doses to tumors. Several radionuclides are evaluated in this context.
The authors maintain that 32P is the most promising isotope and the optimal physical half-life is about two to three times the biologic clearance half-life of the antibodies in the tumor.
