Radioimmunotargeting in ovarian carcinoma patients with indium-111 labeled monoclonal antibody OV-TL 3 F(ab')2: pharmacokinetics, tissue distribution, and tumor imaging

Abstract

Safety and feasibility of tumor targeting with radiolabeled monoclonal antibodies was studied in 28 patients suspected of having ovarian carcinoma, after i.v. administration of 1 mg F(ab′)2 fragments of the murine monoclonal antibody OV‐TL 3, labeled with 150 MBq Indium‐111. There were no adverse reactions, hematological and biochemical serum parameters were stable. In one patient a (subclinical) HAMA‐response was found. Plasma clearance of the immunoconjugate was biphasic with half lives of t½}α = 1.4±0.8 h and t½}β = 25.1±3.7 h, resulting in an optimal time period for immunoscintigraphy at 24–48 h after administration. In 20 patients, undergoing extensive explorative surgery, a total of 271 samples of tumorous and normal tissues were analyzed for radiolabel uptake and tumor presence. The mean uptake in tumor deposits was 5.6 times (range 2.2–19.3) as high as the uptake in normal tissues (fat, peritoneum, muscle, skin). The diagnostic accuracy of immunosctigraphy was compared with that obtained with computer tomography, magnetic resonance imaging, ultrasonography and physical examination. While pelvic localizations were equally well detected by all methods, 48% of the abdominally located tumor deposits were correctly diagnosed by immunoscintigraphy, with only 12% detected by ultrasonography, 8% by CT‐scanning and physical examination, and 6% by MRI. Immunoscintigraphy has potential as a diagnostic tool in ovarian cancer patients and biolocalization results justify further research into the therapeutic application of labeled monoclonal antibodies.