Journal of Clinical Oncology, Vol 15, 1529-1537, Copyright © 1997 by American Society of Clinical Oncology
Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250
MG Steffens, OC Boerman, JC Oosterwijk-Wakka, GO Oosterhof, JA Witjes, EB Koenders, WJ Oyen, WC Buijs, FM Debruyne, FH Corstens and E Oosterwijk
Department of Urology, University Hospital Nijmegen, The Netherlands. msteffens@nugen.azn.nl
PURPOSE: Pharmacokinetics, biodistribution, immunogenicity, and imaging
characteristics of iodine 131 (131I)-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 131I-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 of 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, 131I-cG250 uptake as
high as 0.52% ID/g was observed. However, intratumoral uptake was highly
heterogeneous. 131I-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: 131I-cG250 tumor uptake is
among the highest reported in clinical studies with antitumor antibodies in
solid tumors. Since tumor-sterilizing levels may be guided to the tumor
when high doses 131I-cG250 are administered (> 100 mCi) and cG250
appears to be immunosilent, cG250 is a promising vehicle for
radioimmunotherapy in RCC.
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