Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250

Purpose: Pharmacokinetics, biodistribution, immunogenicity, and imaging characteristics of iodine 131 (I-131)-labeled chimeric monoclonal antibody (mAb) G250 (cG250) were studied in patients with renal cell carcinoma (RCC) to determine the therapeutic potential of this antibody. Patients and Methods: Sixteen patients with RCC received a single intravenous (IV) infusion of 6 mCi I-131-labeled cG250, Five protein dose levels were investigated (2 to 50 mg). Planar scintigraphic images were acquired, and normal tissue biopsies and tumor samples were obtained at surgery (7 days postinjection). The immunogenicity of cG250 was investigated using a sandwich enzyme-linked immunosorbent assay (ELISA) and dosimetric analysis was performed. Results: In all patients with antigen-positive tumors (n = 13), the primary tumors and all known metastases were clearly visualized. Overall uptake, expressed as the percentage 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 observed. However, intratumoral uptake was highly heterogeneous. I-131-cG250 uptake in nontumorous tissues remained low. Dosimetric analysis showed that up to .48 Gy/mCi was guided to the primary tumors. Selected "hot areas" within these tumors received up to .72 Gy/mCi. A bone metastasis received .23 Gy/mCi and regional lymph node metastases received .20 Gy/mCi. Minimal human antichimeric antibody (HACA) levels were detected in two of 16 patients. Conclusion: I-131-cG250 tumor uptake is among the highest reported in clinical studies with antitumor antibodies in solid rumors. Since tumor-sterilising levels may be guided to the tumor when high doses I-131-cG250 are administered (> 100 mCi) and cG250 appears to be immunosilent, cG250 is a promising vehicle for radioimmunotherapy in RCC. (C) 1997 by American Society of Clinical Oncology.