Application of the linear-quadratic model to radioimmunotherapy: Further support for the advantage of longer-lived radionuclides

R. W. Howell, S. M. Goddu, D. V. Rao

Research output: Contribution to journalArticlepeer-review

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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 languageEnglish
Pages (from-to)1861-1869
Number of pages9
JournalJournal of Nuclear Medicine
Volume35
Issue number11
StatePublished - 1994

Keywords

  • biologically equivalent dose
  • dose-rate effects
  • linear-quadratic model
  • radioimmunotherapy
  • radionuclide selection

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