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


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.


CONCLUSIONS
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.
Steffens
M G
MG
Department of Urology, University Hospital Nijmegen, The Netherlands. msteffens@nugen.azn.nl
Boerman
O C
OC
Oosterwijk-Wakka
J C
JC
Oosterhof
G O
GO
Witjes
J A
JA
Koenders
E B
EB
Oyen
W J
WJ
Buijs
W C
WC
Debruyne
F M
FM
Corstens
F H
FH
Oosterwijk
E
E
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000276:immunology* / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D014018:Tissue Distribution; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C106533:G250 monoclonal antibody; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins