Investigators at Memorial Sloan-Kettering have found that using positron emission tomography (PET) imaging in conjunction with a substance known as a radio-labeled antibody can identify the most common and aggressive type of kidney tumor -- helping doctors to determine whether surgery is necessary.
Kidney Tumor Types & PET
Most kidney tumors are discovered incidentally when a patient visits his or her physician with a non-specific complaint involving the digestive system or the muscles, joints, and bones -- or in some cases during cancer follow-up examination. Standard imaging tests conducted during these visits can reveal the presence of kidney lesions, about 90 percent of which are classified as renal cortical tumors. These tumors are subdivided into a number of different tumor types. Sixty-five percent are categorized as clear cell carcinoma, which is aggressive and requires surgical removal. The remaining 35 percent are either benign (non-cancerous) or indolent (slow-growing).
PET is an imaging technique that uses a safe, low dose radioactive substance injected into a patient's bloodstream to produce three-dimensional color images of those substances functioning in the body -- including the metabolic signal of actively growing cancer cells.
New Diagnostic Imaging Technique
In a recent study, Memorial Sloan-Kettering researchers and colleagues from the Ludwig Institute for Cancer Research (LICR) combined PET imaging with a monoclonal antibody called G250, which is known to bind to the aggressive clear cell type of kidney tumor. The G250 monoclonal antibody was originally developed as a potential therapeutic agent by study co-author Dr. Lloyd J. Old, Director of the New York Branch of the LICR and a Memorial Sloan-Kettering investigator. G250 works by reacting against a particular protein that is present in unusually large quantities in clear cell carcinomas.
For the phase I study, G250 was "labeled" with a tracer substance, iodine-124, making it visible during PET scanning. When the radio-labeled antibody, I-cG250, was absorbed by clear cell tumors, those tumors "lit up" on PET scans -- identifying the clear cell tumor subtype that accounts for 54 percent of all renal tumors that currently are surgically removed and 90 percent of tumors that metastasize, or spread. Benign or indolent tumors did not absorb the antibody and, consequently, did not produce the same radioactive "signature" during PET imaging.
The Study and Its Results
Published online in the March 7 Lancet Oncology, the study involved 26 Memorial Sloan-Kettering patients who were scheduled to have surgery to remove kidney tumors. Each of these patients was given I-cG250 in a single injection one week prior to surgery. Three hours before surgery, PET and CT scans were performed. Tissue samples were taken from each of the patients during surgery, and subsequent pathology analysis independent of the PET scanning results classified the tumors as either clear cell carcinoma or non-clear cell carcinoma.
The imaging by PET i-cG250 correctly identified 15 of the 16 patients whose tissue samples were found to be clear cell carcinoma during the post-surgery tissue analysis, producing a 94 percent scanning sensitivity. In addition, all nine of the patients with non-clear cell carcinoma were correctly identified by the PET I-cG250 imaging. (One patient who received immunologically inactive I-cG250 was excluded from the data analysis.) No side effects or other adverse events related to the radio-labeled agent were experienced by any of the patients.
The study's authors suggest that while the results from larger, multi-center trials are required to confirm these findings, non-invasive antibody PET imaging could change the standard of care for patients with kidney cancer. Furthermore, the investigators believe that this form of PET imaging might also be used to track the effectiveness of any future investigational therapies for advanced kidney cancer, as well as to predict tumor recurrence.
Potential Applications
According to Paul Russo, MD, the study's senior author and a urologic cancer surgeon at Memorial Sloan-Kettering, identifying the tumor type as clear cell or non-clear cell before surgery allows the surgeon to formulate a surgical plan, such as extending the limits of the tumor resection or removing the adrenal gland, nearby lymph nodes, or other adjacent structures where advanced disease is identified.
