Radioimmunotherapy of micrometastases: Theoretical evaluation of adjuvant treatment

Failure of current cancer treatment modalities is generally associated with the inability to control distant metastatic disease. This work examines the adjuvant use of radiolabeled antibodies for targeting micrometastases. A Monte Carlo program is used to estimate the number and size distribution of metastases that are present in a given (node-negative) prostate cancer patient population at the time of diagnosis. These results are used in a second program that solves the equations associated with antibody (Ab) diffusion, binding, and dissociation to yield the kinetics of Ab penetration within pre-vascularized micrometastases. These simulated kinetic data are then micrometastasis. Using a two-compartment macroscopic model of Ab distribution, the red marrow dose is also calculated. Calculations are performed for I-123 and for I-131-labeled antibody. With these results, the fraction of the patient population that would benefit from radioimmunotherapy is estimated. The analysis suggests that a single administration of radioimmunotherapy following surgery or external beam radiotherapy will yield a potentially lethal dose ({ge} 20 Gy for I-123 and {ge} 38 Gy for I-131) to 23% of micrometastases present at the time of initial diagnosis without inducing prohibitive red marrow morbidity (absorbed dose {le}2.5 Gy). Multiple courses of radioimmunotherapy, designed to target micrometastases that aremore » initially too small but that eventually reach a targetable size (i.e., 20 {mu}m {le} micromet. radius {le}200{mu}m), will yield a potentially lethal results suggest that approximately 25% of high risk prostate cancer patients (i.e., patients with occult metastases at the time of diagnosis) could benefit from single course of radioimmunotherapy; multiple courses of radioimmunotherapy could benefit 75% of high risk prostate cancer patients.« less