TY - JOUR
T1 - Application of the linear-quadratic model to radioimmunotherapy
T2 - Further support for the advantage of longer-lived radionuclides
AU - Howell, R. W.
AU - Goddu, S. M.
AU - Rao, D. V.
PY - 1994
Y1 - 1994
N2 - 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. Methods: 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. Results: 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. Conclusion: 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.
AB - 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. Methods: 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. Results: 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. Conclusion: 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.
KW - biologically equivalent dose
KW - dose-rate effects
KW - linear-quadratic model
KW - radioimmunotherapy
KW - radionuclide selection
UR - http://www.scopus.com/inward/record.url?scp=0028081071&partnerID=8YFLogxK
M3 - Article
C2 - 7965170
AN - SCOPUS:0028081071
SN - 0161-5505
VL - 35
SP - 1861
EP - 1869
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 11
ER -