Patient biodistribution of intraperitoneally administered Yttrium-90-labeled antibody

Although ⁹⁰Y is one of the best radionuclides for radioimmunotherapeutic applications, the lack of gamma rays in its decay complicate the estimation of radiation dose since its biodistribution cannot be accurately determined by external imaging. A limited clinical trial has been conducted with tracer doses (1 mCi) of ⁹⁰Y in five patients who then received second-look surgery such that tissue samples were obtained for accurate radioactivity quantitation by in vitro counting. The anti-ovarian antibody OC-125 as the F(ab')₂ fragment was coupled with diethylenetriaminepentaacetic acid, radiolabeled with ⁹⁰Y and administered intraperitoneally to patients with suspected or documented ovarian cancer. Size exclusion and ion exchange high performance liquid chormatography analysis of patient ascitic fluid and serum samples showed no evidence of radiolabeled instability although a high molecular weight species (presumably immune complex) was observed in three patients. Total urinary excretion of radioactivity prior to surgery averaged 7% of the administered radioactivity while at surgery the mean organ accumulation was 8% of the administered radioactivity in serum, 10% in liver, 7% in bone marrow, and 19% in bone with large patient to patient variation. The mean tumor/normal tissue radioactivity ratio varied between 3 and 25. On the assumption that the above radioactivity levels were achieved immediately following administration, that the radioactivity remained in situ until decayed and that the dimensions of tumor were sufficient to completely attenuate the emissions of ⁹⁰Y, the dose to tumor for a 1-mCi administration would be ~50 rad with normal tissues receiving ~8 rad.