Estimates of dose to intraperitoneal micrometastases from alpha and beta emitters in radioimmunotherapy

Intraperitoneal metastases from ovarian and other gynecologic tumors are a significant source of treatment failure. In recent years, investigators have used radiolabeled monoclonal antibodies to treat this disease with encouraging results. We have developed a dose calculational technique which generates isodose distributions from intraperitoneally administered alpha and beta particle emitters. In this study we apply the calculations to tissue biopsy samples to determine the adequacy of dose to ovarian micrometastases. Tissue samples from staging biopsies at the time of surgical debulking are scanned to identify small metastases. The patient population studied comprised those with ovarian disease who based on clinical criteria would be considered good candidates for intraperitoneal radioimmunotherapy. The regions of interest (which include the tumor and surface of the peritoneum) are digitized and tumor volumes are contoured. Dose calculations based on the modeling of intraperitoneally administered antibodies radiolabeled with various isotopes is performed and the minimum dose to tumor and normal tissue is assessed. For example, with tumor uptake of 0.1% injected dose per gram of tissue, the surface tumor dose from alpha emitters is up to 45,000 rads. The dose falls to 6000 rads at approximately 40 microns from the peritoneal surface. The surface dose from 20 mCi 90Y administered in 1500 ml saline is up to 10,000 rads, and at a 2-mm depth, approximately 2000 rads. From our calculation dose distribution from radioimmunotherapy varies as a function of physical characteristics of the isotope, absorption of activity, and amount of disease being treated.