Emerging isotopes and ligands expand future role for PET/CT

The fusion of anatomic and functional data in PET/CT scans has received an enthusiastic welcome from both radiologists and nuclear medicine physicians. The combination of modalities has benefited oncology in particular. The use of new radioisotopes and ligands will broaden the scope of PET/CT in diagnosis, therapy, and clinical research, according to Prof. Peter Ell, director of the Institute of Nuclear Medicine at University College London.

About 95% of PET/CT studies are linked to oncology applications, due to the widespread use of the PET tracer fluorine-18 FDG. FDG is particularly effective at revealing areas of increased glucose uptake, a key trait of cancerous cells. Tracers that home in on alternative physiological mechanisms have the potential to alter the status quo, and their development is likely to occur sooner rather than later, Ell told delegates at a British Institute of Radiology meeting in May.

"From a clinical point of view, most of the work is still using FDG-PET. In the future, I predict that the relative percentages of isotopes and combinations of ligands will change," he said. "Oncology may still account for 70% of PET/CT work, but cardiology will grow quite rapidly, psychiatry will grow rapidly, and perhaps musculoskeletal applications will also have an important role to play."

The radioisotope gallium-68 will be a leading contender for widespread use, Ell said. Other candidates for clinical PET/CT include copper-64 and iodine-124. One possible application for Ga-68 is in imaging prostate cancer and its metastases, which express membrane GLUT transporters poorly and are therefore among the few malignancies that escape detection with FDG.

A number of novel F-18 ligands are also under consideration. Some of the most promising work in process involves ligands targeting the plaques associated with Alzheimer's disease.

"This will open up an entire new area of investigation in patients with early cognitive decline," Ell said.

PET/CT's prime use in oncology is to assess the extent and severity of disease. Research has shown, for instance, that PET/CT prevents unnecessary surgery in one of every five cases of non-small cell lung cancer, and use of the combined modality for staging this pathology is cost-effective.

Lymphoma is now accepted as an important indication for PET/CT. The combined modality is also considered useful for primary staging of Hodgkin's and non-Hodgkin's lymphoma. It is better than CT alone at staging nodal and extranodal disease and for post-therapy evaluations. A single PET/CT scan is sufficient for prognosis following treatment for aggressive Hodgkin's and non-Hodgkin's lymphoma, yet hematologists still request multiple studies, Ell said.

"Despite guidelines, one-fifth of patients are being scanned more than once," he said.

Prospective directions for PET/CT include treatment monitoring and clinical drug trials. Based on research showing that a metabolic response precedes an increase or decrease in tumor size, changes observed on a PET scan could act as a surrogate marker of drug efficacy. Metabolic response in lymphoma and germ cell cancers can be seen in a matter of hours on PET, Ell said. He showed images acquired from a patient with germ cell cancer before and two weeks after treatment. PET imaging confirmed that the drug, designed to shut down glucose transporters in the lymph nodes, worked rapidly. Measuring changes to standard uptake values would provide a quantitative measure of efficacy.

Little work has been published on radiotherapy planning with PET/CT, but a collaborative investigation of this subject is in early stages at UCL. The researchers hope to determine whether the combination of anatomic and metabolic data will change patient management in this application as it has elsewhere.

"For the first time in 30 years in nuclear medicine, I no longer look at fuzzy images," Ell said. "It is absolutely fantastic. The images by themselves make the case for PET/CT."