New Developments in PET Aid Diagnosis, Rx of Cancers

NEW YORK—Nuclear medicine-based imaging techniques are now being used to refine treatment strategies for cancer patients, with positron emission tomography (PET) at the forefront. Patients with complex cancers of the brain, head and neck, thyroid, and lung are now able to receive more refined and accurate diagnoses through new PET techniques, four speakers said at a nuclear medicine conference sponsored by Memorial Sloan-Kettering Cancer Center and Johns Hopkins University School of Medicine.

Brain Tumors

Fluorodeoxyglucose (FDG) is an agent taken up by tumor cells exhibiting increased glycolysis. “Because such increased metabolism is often associated with malignant tumors, FDG-PET imaging is widely used in studying brain tumors,” said Ronald G. Blasberg, MD, attending neurologist, Memorial Sloan-Kettering Cancer Center, and professor of neurology, Weill Medical College of Cornell University.

However, there are problems associated with FDG-PET imaging of the brain. Dr. Blasberg pointed out that while low-grade brain tumors appear hypo-metabolic on an FDG-PET scan and high-grade tumors usually have hypermetabolic foci (ie, 18F-FDG is taken up and appears as a bright spot on the PET scan), there is often a heterogeneous distribution of FDG signal within a given tumor.

“Although more FDG uptake can usually equate with reduced patient survival, the mixed uptake patterns complicate the diagnosis and management of brain cancers,” he explained.

To obviate some of these imaging challenges, Dr. Blasberg described a computer-aided process called “registration,” whereby FDG-PET and MR images are digitally superimposed upon each other. “By using various algorithms, the contrast-enhancing zone will appear metabolically active, giving a more accurate assessment of tumor physiology than the MR image alone,” he said.

Dr. Blasberg also described using other iodine-labeled radiopharmaceuticals like tyrosine, methionine, or thymidine to study amino acid transport and DNA synthesis levels, for example.

“Combinations of FDG and methionine scanning can demonstrate changes in transport levels within tumor cells, and this is a key feature of brain tumors that can be used to assess treatment response,” he noted. Since there is a functional relationship between FDG uptake, rate of malignancy, and survival, such techniques can also benefit other cancer types.

Head and Neck, Lung Cancer

Homer A. Macapinlac, MD, clinical director of the PET facility at Sloan-Kettering, said that FDG-PET imaging is now being used in the staging, post-treatment, and monitoring phases of head and neck cancer management.

“Although issues of instrument sensitivity still need to be refined, various reports indicate that FDG-PET is more accurate than CT or MRI in identifying both primary and recurrent head and neck tumors,” he said.

Importantly, Dr. Macapinlac cited a case in which FDG-PET scans revealed a tumor hidden beneath healthy tissue in the posterior nasopharynx. This resulted in surgical resection, avoiding the extensive radiation treatment and chemotherapy that would have been employed had the tumor remained undetected.

Similarly, FDG-PET is breaking new ground in distinguishing benign from malignant solitary pulmonary nodules, said Henry Wagner, MD, professor of medicine, radiology, and environmental health, Johns Hopkins School of Hygiene and Public Health.

“By using dual coincidence gamma cameras with FDG, a 97% sensitivity and 80% specificity was shown in identifying proven malignant lung lesions,” he said. These data in 96 patients were published in the April 1999 issue of the Journal of Nuclear Medicine (40:574-578, 1999).

Steven M. Larson, MD, chief of nuclear medicine, Sloan-Kettering, detailed how sequential use of FDG-PET and radiolabeled iodine scans can affect the management of thyroid cancer patients.

“Despite a low overall mortality rate, a high percentage of fatalities are due to the less well-differentiated thyroid cancers,” he said. Since these tumors have little or no iodine-concentrating activity, radiolabeled iodine scans can yield false-negative results. Thus, FDG-PET scanning is also warranted.

Dr. Larson reported a study of 96 patients with thyroid cancer, 37 of whom had negative whole-body iodine scans. Of these 37 patients, 22 had positive FDG- PET scans. Furthermore, 18 exhibited high thyroglobulin (Tg) levels, and 19 had low Tg levels, both indicators of residual tumor.

“While FDG-PET scans in these patients positively identified tumor, Tg levels themselves were a more sensitive detector of residual cancer,” Dr. Larson said. “The key point was that in 22 of the 37 patients, the FDG-PET scan results permitted correct clinical changes in treatments,” he said.

Dr. Larson also described separate data on the benefits of using the positron-emitter iodine-124 (124I) in thyroid cancer scanning. Preliminary data indicate that using this isotope can increase the sensitivity and resolution of the PET scan. He said that 124I-PET studies in five patients with thyroid cancer revealed tumors that were otherwise occult.