Few events in the imaging arena have commanded more attention than the current revolution going on in nuclear medicine. The spark for this revolution is the development of technology that permits the widespread use of the powerful tumor imaging agent, F-18 fluorodeoxyglucose (FDG). Over the last 20 years, positron emission tomography (PET) imaging has developed an impressive body of data concerning FDG applications in oncology.

As Dr. Henry Wagner points out below, these advances were restricted to only a limited number of patients. The capital cost of dedicated PET equipment and the lack of widespread availability of FDG impeded the spread of the technology. Commercial radiopharmacies already are delivering FDG and will be expanding their role in the future.

With the advent of gamma camera FDG imaging, the number of sites capable of imaging FDG will increase by 50% this year alone. Although there are limitations to the technology, overall it enhances the diagnosis of tumor distribution in a number of diseases, ranging from lymphoma to lung cancer. Multicenter clinical trials currently are under way to define more precisely the accuracy and document the impact on patient management of FDG imaging on gamma cameras.

Indeed, we are fortunate to have Dr. Henry N. Wagner, Jr., prepare the review below for us. Dr. Wagner is one of the best known nuclear physicians in the country. His involvement with PET imaging over the last few years gives him a unique perspective on this issue. We are pleased to present this brief introduction to the state of a new art.

Robert E. Henkin, MD, FACNP, FACR

Professor, Department of Nuclear Medicine

Loyola University Medical Center

Maywood, IL

A postgraduate course entitled "Nuclear Oncology: From Genetics to Patient Care," was held at Johns Hopkins Medical Institutions between April 7 and 9, 1997. Investigators from around the world presented increasing evidence that Fluorine-18 deoxyglucose coincidence imaging helps detect metastatic cancer of the head and neck, breast, lung, liver, and colon.

Dr. Peter Valk, of the Northern California PET Imaging Center, who has performed over 3,000 PET studies with FDG in patients with cancer, reported the impact of FDG studies in the care of patients with brain tumors, head and neck cancer, and non-small cell lung cancer. In those patients with brain tumors, the FDG study is indicated when an MRI or CT shows new areas of contrast enhancement that may represent either residual or recurrent tumor or radiation necrosis. The demonstration of major survival differences between patients with and without FDG accumulation in these lesions further validates the use of PET for differentiation of recurrent tumor from radiation necrosis.

Dr. Valk further described a study comprised of 33 patients with known or suspected recurrence of squamous cell cancer of the head and neck. FDG imaging was more accurate than CT or MRI in detecting local or regional recurrence. FDG studies often revealed unsuspected distant metastatic cancer. In 99 patients with lung cancer, FDG was more accurate than CT in the diagnosis of metastatic mediastinal nodes and distant metastases. Detection of unsuspected metastatic disease by PET resulted in a decrease in the number of patients who underwent thoracotomy directed at the removal of all cancer.1-3

Dr. Richard Wahl, of the University of Michigan, summarized a worldwide literature search on the use of PET FDG studies to separate lung cancer from benign disease in patients with solitary pulmonary nodules on chest radiographs. FDG was useful in nodules greater than 1 cm in diameter. A recent multicenter study found PET to be greater than 90% sensitive in determining whether a solitary pulmonary nodule was malignant, with an acceptably small number of false positives.

Dr. David Mankoff reviewed data concerning FDG studies in breast cancer. Whole-body PET imaging was used to detect recurrent or metastatic disease. Both FDG and carbon-11 methionine were helpful in determining the response of the lesions to therapy. At Mankoff's institution, the University of Washington, FDG PET studies provided new staging information in over 60% of the patients and significantly affected therapy in approximately 89% of the cases.

Dr. Paul Shreve, of the University of Michigan, reported his preliminary results in the use of dual-headed coincidence imaging with a modified SPECT system. In studies of 34 patients with non-small cell lung cancer, he compared the results of dual-headed gamma camera coincidence imaging to a dedicated PET system. Dr. Shreve reported that, in nearly every case, the results were the same; however, in many cases, the definition of the lesions was better with the dedicated PET than with the dual-headed system.

The dual-headed coincidence imaging system used by Dr. Shreve was developed by ADAC Laboratories and is based upon earlier systems. The use of a gamma camera to image positron emitting radionuclides, such as Fluorine-18, was first described by Hal Anger in 1957. Gerd Muehllehner then advanced dual-head coincidence imaging in the 1970s using analogue detectors, but the images were limited by low count rate capabilities. He subsequently developed a dedicated PET imaging system, called PennPET, in the mid 1980s and formed UGM Laboratories. The PennPET system uses gamma camera detectors built with high-speed digital electronics to achieve the necessary counting rates.

ADAC Laboratories and UGM further developed the digital electronics to enable both single photon and positron coincidence imaging to be performed with the same dual-headed gamma camera. The positron imaging is called molecular coincidence detection (MCD) and was shown by ADAC Laboratories at the annual meeting of the Society of Nuclear Medicine in 1995. The results were impressive, and the brain images were deemed "Image of the Year."

Examples of two FDG/MCD studies of patients with lung cancer are shown in figures 1 and 2. CL, a patient of Dr. John Sweeney at Boone Hospital, had a positive CT scan revealing a lesion in the left lower lobe of the lung. On the MCD study, the lesion seen on the CT had a high FDG uptake. There was no evidence of lymph node involvement.

EJ was a patient of Dr. George Sfakianakis at the University of Miami. The CT scan showed tumor in the left upper lobe but no lymphadenopathy. The FDG/MCD study showed avid accumulation of FDG in both the primary tumor and a mediastinal node. The patient had a left upper lobectomy. Pathology results were positive for squamous cell carcinoma and metastases in the visualized perihilar lymph node.

One of the major advantages of a multipurpose dual-headed camera is that a single imaging device can perform both single-photon imaging and coincidence imaging. These systems retain the capability of imaging tracers emitting single photons as well. Radiopharmaceuticals such as Tc-99m sestamibi or similar agents used for the detection of multidrug resistance to cancer chemotherapeutic agents may be imaged. These devices also may study receptor-imaging agents, such as In-111 somatostatin analogues.

The addition of the coincidence capability to the gamma camera, by increasing the crystal thickness to five-eighths of an inch, has not resulted in any significant decrease in the effectiveness of the camera for technetium-99m or other single-photon-emitting tracers. The thicker crystal increases the detection efficiency for Tc-99m by 10%, and higher energy emitters, such as I-131, Ga-67, and In-111, have even larger increases in the detection efficiency. This should improve the image quality of scans involving these radionuclides even further. Thirty systems of this type have been installed by March 1997.

The coincidence system has four to eight times greater counting efficiency than the use of high-energy collimators for FDG collimator-based SPECT for positron-emitters. The dual-headed coincidence systems have a larger axial field of view than dedicated PET systems and, therefore, can image a larger area of the patient with a single acquisition. The spatial resolution of dual-headed coincidence imaging is less than 5 mm, which compares favorably with dedicated PET. Most of the dedicated PET systems, however, have a full ring of detectors around the patient and, therefore, have a higher geometric efficiency that leads to higher image quality in clinical studies. Another advantage of dedicated PET systems is the higher count rate capability. This higher count rate capability permits the use of 10 mCi of FDG, as compared to 5 mCi used in the coincidence gamma camera system.

At the conclusion of the conference, the attendees unanimously agreed that FDG imaging will play a major role in the care of many oncology patients. Half of them responded that the approach that they themselves would take is to image FDG with a dual-headed coincidence system.

The use of dual-headed coincidence systems will allow more widespread use of FDG imaging for the management of cancer patients. Centers that previously have not had access to PET technology may now be able to offer their patients FDG imaging for oncology evaluations. AR

References

1. Gupta NC, Frank AR, Dewan NA, et al: Solitary pulmonary nodules: Detection of malignancy with PET with 2-[F-18]-fluoro-2-deoxyglucose. Radiology 184:441-444, 1992.

2. Knopp MV, Bischoff HG: Evaluation of pulmonary lesions with positron emission tomography. Radiologe 34:588-591, 1994.

3. Valk P: Clinical application and cost-effectiveness of PET in colon cancer. Nucl Med Biol 23:737-743, 1996.