G250 PET characterizes clear-cell renal carcinoma

PET imaging using the iodine-124-labeled antibody called chimeric G250 (124I-cG250) can accurately identify clear-cell renal carcinoma, according to a study by researchers at Memorial Sloan-Kettering Cancer Center in New York City. Findings could lead to an improvement in the clinical management of patients with kidney tumors.

The National Cancer Institute estimates that approximately one person in 7500 in the U.S. will develop some type of renal cell carcinoma each year. A third of them will eventually die from the disease. About 90% of renal metastases, which carry the poorest prognosis, are clear-cell RCCs.

This prospective clinical trial is the first to show that PET with a radiolabeled antibody is sensitive and specific enough to identify this histologic subtype, said principal investigator Dr. Chaitanya Divgi, who is now chief of nuclear medicine and clinical molecular imaging at the University of Pennsylvania.

Physicians could use antibody PET to decide the right surgical approach in patients with renal masses or determine the efficacy of molecular therapies. Patients with equivocal kidney tumors could be screened for surgery, since antibody PET-negative patients could be watched rather than operated upon, Divgi said.

The study was published in the April issue of The Lancet Oncology.

Twenty-five patients scheduled for resection of renal masses prospectively underwent 124I-cG250 PET before surgery. Investigators graded images as positive or negative for antibody uptake. A pathologist blinded to PET results classified the histologic type of tumor specimens.

The researchers found that 124I-cG250 PET identified 15 of 16 clear-cell RCCs. None of the other RCC subtypes showed positive tracer uptake, suggesting a negative scan is highly predictive of a less aggressive phenotype. The single 185 MBq/10 mg antibody injection proved safe with no adverse side effects. 124I-cG250 PET imaging of clear-cell kidney carcinoma provided sensitivity, specificity, and positive and negative predictive values of 94%, 100%, 100%, and 90%, respectively.

The monoclonal antibody G250 had been intended originally as a therapeutic agent, since it binds to and attacks an enzyme present in clear-cell RCC. The high uptake of G250 in renal carcinoma compared with other solid tumors makes it ideal for use with PET.

The agent could change the standard of care for patients in the workup and management of clinically localized renal masses and become an alternative to biopsy, said senior investigator Dr. Paul Russo, a urologic cancer surgeon at MSKCC. G250 PET could also be used to gauge the extent and aggressiveness of a patient's cancer before intervention, evaluate treatment response, and predict the likelihood of recurrence.

Although these findings from a single institution need validation via a multicenter study, they are promising, according to Dr. R. Edward Coleman, chief of nuclear medicine at Duke University.

"We have not been able to be specific about cell types of cancer in the past, and the results of this study suggest that we will be able to in the future. As molecular therapies are becoming more specific, molecular diagnoses need to be more specific. Perhaps this is a step in that direction," Coleman said.

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