NEW YORK -- PET imaging with a radiolabeled monoclonal antibody can identify aggressive clear-cell renal carcinoma and help urologists decide whether surgery is needed, researchers here reported.
NEW YORK, March 7 -- PET imaging with a radiolabeled monoclonal antibody can identify aggressive clear-cell renal carcinoma and help urologists decide whether surgery is needed, researchers here reported.
In an open-label phase I study of 25 patients with renal masses, 15 of 16 clear-cell renal carcinomas were identified accurately using PET with the iodine-125-labeled monoclonal antibody cG250. Antibody cG250 reacts against carbonic anhydrase-IX, which is over-expressed in clear-cell renal carcinomas.
All nine non-clear-cell renal masses were negative for the tracer, according to an online report in the April issue of Lancet Oncology.
The sensitivity of 125 I-cG250 PET for clear-cell kidney carcinoma in this trial was 94% (95% CI 70%-100%), said Chaitanya Divgi, M.D., of the Memorial Sloan-Kettering Cancer Center, now at the University of Pennsylvania, and colleagues.
The negative predictive value was 90% (CI 55%-100%), and specificity and positive predictive accuracy were both 100% (CI 66%-100% and 78%-100%, respectively), the researchers said.
The PET-negative clear-cell carcinoma in one patient was probably negative because of extended necrosis in the analyzed tissue section, the investigators said.
All patients tolerated the antibody infusions, and there were no allergic or other adverse events, including toxic effects related to the study agent.
All tumors deemed positive had tumor-to-healthy-kidney ratios of 5.3 to 1, while all negative tumors had ratios of 1.4 to 1, or less.
Antibody PET could end up changing the standard of care for patients with kidney cancer, the authors wrote. The method would have a role in the work-up and management strategies for clinically localized renal masses and as an alternative to biopsy for distinguishing renal lesions, the researchers said.
Stratification of patients with renal masses by 125 I-cG250 would also be useful in comorbidly ill patients with cG250-negative renal masses, and in partial nephrectomy for larger cG250-negative renal masses that are technically challenging, the researchers said.
The benefits, they noted, would be achievement of local tumor control, maintenance of renal function, and histology assessment of multifocal and bilateral renal tumors. The researchers wrote that they did not include size-exclusion criteria in this proof-of-concept study, but they intend to do so in a future trial.
This study was done primarily to assess, noninvasively, the immunophenotype of the primary tumor, the investigators said. However, in two patients, metastatic disease was found: a solitary lung metastasis in one patient and extensive metastatic involvement of the precaval lymph nodes in the other.
Other studies have shown that saturation of biliary sites is possible with antibody doses over 5 mg. Therefore, a dose of 10 mg was chosen for this study, they added.
Antibody PET can provide urologists with presurgical information that can guide crucial aspects of surgical management, the authors said. G250 PET may ultimately be used not only to determine the aggressiveness and extent of a patient's disease prior to surgery, but also to measure the therapeutic effects of treatment and the likelihood of recurrence.
"To our knowledge," Dr. Divgi and colleagues said, "this is the first application of PET imaging in a prospective clinical trial in patients with renal tumors. The promising results of this trial have stimulated interest in a larger, multicenter trial to confirm these findings."