TARGETING OF RENAL-CELL CARCINOMA WITH IODINE-131-LABELED CHIMERIC MONOCLONAL-ANTIBODY G250

Purpose: Pharmacokinetics, biodistribution, immunogenicity, and imagin g characteristics of iodine 131 (I-131)-labeled chimeric monoclonal an tibody (mAb) G250 (cG250) were studied in patients with renal cell car cinoma (RCC) to determine the therapeutic potential of this antibody. Patients and Methods: Sixteen patients with RCC received a single intr avenous (IV) infusion of 6 mCi I-131-labeled cG250, Five protein dose levels were investigated (2 to 50 mg). Planar scintigraphic images wer e acquired, and normal tissue biopsies and tumor samples were obtained at surgery (7 days postinjection). The immunogenicity of cG250 was in vestigated using a sandwich enzyme-linked immunosorbent assay (ELISA) and dosimetric analysis was performed. Results: In all patients with a ntigen-positive tumors (n = 13), the primary tumors and all known meta stases were clearly visualized. Overall uptake, expressed as the perce ntage of the injected dose (%ID), in the primary tumors ranged from 2. 4 to 9.0. Focally, I-131-cG250 uptake as high as 0.52% ID/g was observ ed. However, intratumoral uptake was highly heterogeneous. I-131-cG250 uptake in nontumorous tissues remained low. Dosimetric analysis showe d that up to .48 Gy/mCi was guided to the primary tumors. Selected ''h ot areas'' within these tumors received up to .72 Gy/mCi. A bone metas tasis received .23 Gy/mCi and regional lymph node metastases received .20 Gy/mCi. Minimal human antichimeric antibody (HACA) levels were det ected in two of 16 patients. Conclusion: I-131-cG250 tumor uptake is a mong the highest reported in clinical studies with antitumor antibodie s in solid rumors. Since tumor-sterilising levels may be guided to the tumor when high doses I-131-cG250 are administered (> 100 mCi) and cG 250 appears to be immunosilent, cG250 is a promising vehicle for radio immunotherapy in RCC. (C) 1997 by American Society of Clinical Oncolog y.