Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250.
OBJECTIVE
To define the imaging and biodistribution characteristics of iodine 131-labeled monoclonal antibody (mAb) G250 (131I-mAbG250), which recognizes a cell-surface antigen expressed by human renal cell carcinoma (RCC).


METHODS
G250 is a cell-surface antigen recognized by mAbG250 expressed by RCC but not detected in normal kidney. Clear-cell RCC, the most frequent form of RCC, shows homogeneous expression of G250, whereas non-clear-cell RCC and cancers derived from other organs generally do not express G250. Expression in normal tissues is highly restricted and limited to large bile ducts and gastric epithelium. 131I-mAbG250 was administered intravenously (IV) to 16 patients with RCC 7 to 8 days before surgery at five dose levels, with at least three patients entered at each dose level.


RESULTS
Clear tumor images were observed in 12 patients with G250-positive tumors and in one of three patients with G250-negative tumors. Imaged lesions in the peritoneal cavity were confirmed at surgery. The smallest lesion visualized was 8 mm in diameter. The specificity of 131I-mAbG250 localization to tumor tissue was established by radioactivity measurements, autoradiography, and immunohistochemistry of biopsied tissues, and technetium 99-human serum albumin blood-flow studies. The fraction of the injected 131I-mAbG250 dose per gram tumor (%ID/g tumor) localized in G250-positive tumors showed a broad range, but reached levels as high as 0.02% to 0.12%.


CONCLUSIONS
131I-mAbG250 localized specifically to G250 antigen-positive RCC and seems to have considerable potential as an imaging agent in RCC patients. 131I-mAbG250 uptake in the tumors, relative as well as absolute, are among the highest reported for tumor biopsies obtained 8 days after IV mAb administration. Based on the specific localization and high accumulation, mAb G250 may have therapeutic potential.
Oosterwijk
E
E
Ludwig Institute for Cancer Research, New York, NY.
Bander
N H
NH
Divgi
C R
CR
Welt
S
S
Wakka
J C
JC
Finn
R D
RD
Carswell
E A
EA
Larson
S M
SM
Warnaar
S O
SO
Fleuren
G J
GJ
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D001345:Autoradiography; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000032:analysis / Q000493:pharmacokinetics; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D016719:Radioimmunodetection / Q000009:adverse effects; D013668:Technetium Tc 99m Aggregated Albumin
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D013668:Technetium Tc 99m Aggregated Albumin