RADIOIMMUNOTHERAPY OF MEDULLARY-THYROID CANCER WITH IODINE-131-LABELED ANTI-CEA ANTIBODIES

This study evaluates the pharmacokinetics, dosimetry, toxicity and the rapeutic potential of radiolabeled NP-4 and MN-14 anti-CEA antibodies in medullary thyroid cancer (MTC). Methods: Eighteen patients with adv anced MTC entered exploratory clinical studies with therapeutic doses of I-131-labeled NP-4 and MN-14 murine monoclonal antibodies (MAbs) re active with carcinoembryonic antigen (CEA). Doses administered ranged from 46 mCi for I-131-MN-14 IgG to 195 mCi for I-131-MN-14 F(ab)(2) in patients negative for human anti-mouse antibodies (HAMA). Results: Th e radioconjugate blood half-life (T1/2) for the whole IgG was 42.5 +/- 5.0 hr compared to 18.8 +/- 4.1 hr for the bivalent fragments. Tumor doses of 17.5 +/- 11.0 and 11.4 +/- 6.3 cGy/mCi were estimated for I-1 31-MN-14 IgG and F(ab)(2), respectively. Tumor/red marrow dose ratios exceeded 3:1 for most lesions. Red marrow doses of up to 350 cGy gener ally could be delivered with < grade 4 toxicity. Seven of 14 evaluable patients showed evidence of anti-tumor effects lasting up to 26 month s, based on physical exam, tumor markers or computed tomography. Concl usion: This study demonstrates that-anti-CEA MAbs may be suitable for radioimmunotherapy of metastatic or recurrent MTC.