PHARMACOKINETICS AND NORMAL ORGAN DOSIMETRY FOLLOWING INTRAPERITONEALRHENIUM-186-LABELED MONOCLONAL-ANTIBODY

Pharmacokinetics, biodistribution and radiation dose estimates followi ng intraperitoneal administration of a Re-186-labeled murine antibody, NR-LU-10, were assessed in 27 patients with advanced ovarian cancer. Methods: Quantitative gamma camera imaging and gamma counting of serum and intraperitoneal fluid radioactivity were used to obtain data for dosimetry estimation. The MIRD intraperitoneal model was used to estim ate dose to normal organs from radioactivity within the peritoneal cav ity. The absorbed dose to normal peritoneum was estimated in two ways: from the gamma camera activity and peritoneal fluid samples. Results: Serum activity peaked at 44 hr and depended on the concentration of r adioactivity in the peritoneal fluid. Mean cumulative urinary excretio n of Re-186 was 50% by 140 hr. Estimates of radiation absorbed dose to normal organs in rad/mCi administered (mean +/- s.d.) were whole body 0.7 +/- 0.3; marrow 0.4 +/- 0.1; liver 1.9 +/- 0.9; lungs 1.3 +/- 0.7 ; kidneys 0.2 +/- 0.2; intestine 0.2 +/- 0.2. Peritoneal surface dose estimates varied depending on the volume of fluid infused and the meth od of dose determination. Using gamma camera data, the peritoneal dose ranged from 7 to 36 rad/mCi. Using peritoneal fluid sample data, the dose ranged from 2 to 25 rad/mCi. Significant myelosuppression was obs erved at marrow doses above 100 rad. Conclusion: Noninvasive methods o f dose estimation for intraperitoneal administration of radioimmunocon jugates provide reasonable estimates when compared with previously des cribed methods.