Modeling analysis of platinum-195m for targeting individual blood-borne cells in adjuvant radioimmunotherapy.

Abstract

The inability to eradicate a population of single, isolated, blood-borne tumor cells with the radionuclides currently in use may limit the efficacy of adjuvant radioimmunotherapy. We have examined the possibility of sterilizing single blood-borne cells using surface-bound emitters of Auger and conversion electrons. The number of cell-surface decays required for 99% sterilization was found by using the linear-quadratic model of cell survival (alpha = 0.3 Gy-1, alpha/beta = 10 Gy) to transform absorbed dose to survival probability. The absorbed dose to the center of the cell was calculated by evaluating the point dose kernel at the cell radius of 6 microns and multiplying it by the number of surface decays. A two-compartment model of whole-body pharmacokinetics was used to obtain the red marrow dose corresponding to a given number of cell-surface decays. Platinum-195m (T 1/2 = 4 days) proves to be a particularly effective radionuclide. The 195mPt protocol requires 1.2 GBq of injected activity and is calculated to give an average red-marrow dose of 1.23 Gy, well within marrow tolerance. Analysis of the targeting efficiency as a function of cell radius reveals that 195mPt is expected to sterilize cells with radii up to 8 microns without delivering more than 2.5 Gy to red marrow. It also emits photons that are appropriate for external imaging and has been used to study the biodistribution of cisplatin in humans. High-specific activity 195mPt may be obtained by decay of cyclotron-produced 195mIr (T 1/2 = 3.8 hr).