Abstract
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.
| Original language | American English |
|---|---|
| Pages (from-to) | 1861-1869 |
| Number of pages | 9 |
| Journal | Journal of Nuclear Medicine |
| Volume | 35 |
| Issue number | 11 |
| State | Published - 1994 |
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging
Keywords
- biologically equivalent dose
- dose-rate effects
- linear-quadratic model
- radioimmunotherapy
- radionuclide selection