Proliferation and the advantage of longer-lived radionuclides in radioimmunotherapy

Med Phys. 1998 Jan;25(1):37-42. doi: 10.1118/1.598171.

Abstract

In our previous study we used the linear-quadratic model [J. Nucl. Med. 35, 1861 (1994)] to confirm our initial finding, based on the time-dose-fractionation model [J. Nucl. Med. 34, 1801 (1993)], that longer-lived radionuclides (e.g., 32P, 91Y) can offer a substantial therapeutic advantage over the shorter-lived radionuclides presently used in radioimmunotherapy (e.g., 90Y). The original calculations using the linear-quadratic (LQ) model did not account for proliferation of the tumor and critical bone marrow tissues. It has been suggested that inclusion of a proliferation term in the LQ model can have a substantial impact on the biologically effective dose (BED). With this in mind, we have reexamined the therapeutic efficacy of longer versus short-lived radionuclides using the LQ model replete with proliferation terms for tumor and bone marrow. Relative advantage factors (RAF), which quantify the overall therapeutic advantage of a long-lived compared to short-lived radionuclide, were calculated accordingly. While the extrapolated initial dose rate required to achieve a given BED can be affected by the inclusion of proliferation terms for both the tumor and marrow, the relative advantage factors for the longer-lived radionuclides were not significantly affected. Longer-lived radionuclides such as (114m)In and 91Y are about three times more therapeutically effective than the shorter-lived 90Y which is currently used in RIT. In other words, for a given therapeutic effect in the tumor, a longer-lived radionuclide can result in a lower deleterious effect to the bone marrow than a short-lived radionuclide. Given that bone marrow is generally considered to be the dose-limiting organ, these results have important implications for radioimmunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Brachytherapy
  • Dose Fractionation, Radiation
  • Half-Life
  • Humans
  • Models, Theoretical*
  • Neoplasms / radiotherapy*
  • Radioimmunotherapy*
  • Radioisotopes / chemistry*
  • Radioisotopes / therapeutic use
  • Radiotherapy Dosage
  • Radiotherapy Planning, Computer-Assisted*

Substances

  • Radioisotopes