AMI showcases advanced tracer strategies

The 2006 meeting of the Academy of Molecular Imaging occupied the middle ground between meetings of its two sister societies, the eminently scientific Society for Molecular Imaging and the clinically oriented Society of Nuclear Medicine.

The AMI featured a bit of both in its tripartite sessions representing the clinical Institute for Clinical PET, the pharmaceutical Society of Non-Invasive Imaging in Drug Development, and the scientific Institute for Molecular Imaging.

The Orlando meeting drew practicing nuclear physicians and radiologists with reports of advancements in clinical imaging. It was clear from Dr. Perry W. Grigby, a radiation oncologist at Washington University in St. Louis, that FDG-PET/CT improves staging accuracy and offers a powerful means of predicting response to therapy. Data presented by Dr. Annika Loft, chief physician in the Center of Diagnostic Investigations at Copenhagen University Hospital in Denmark, showed that PET/CT is 91% accurate for staging disease.

Other sessions addressed the practicalities of participating in the American College of Radiology Imaging Network's PET Registry and the implications of impending Medicare rate cuts on PET. PET/CT still represents less than 1% of all diagnostic imaging, according to Ruth Tesar, president of ImageMed in Sacramento. In 2004, the average service performed 834 billable procedures, and the industry was projected to have grown 23% in 2005.

That providential news was tempered by warnings of a perfect storm hitting radiology reimbursement. Medicare cuts could lead to a $136 million reduction in technical fees for nuclear medicine by fiscal 2007, said Denise Merlino, president of Merlino Healthcare Consulting in Stoneham, MA. MRI, CT angiography, and ultrasound could see cuts totaling $848 million.

Dr. Sandra Horning, president of the American Society of Clinical Oncology, credited better therapies and diagnostic techniques for measurably improved outcomes for cancer patients. Nearly two-thirds of all cancer patients now survive at least five years compared with only half 25 years ago. Prospects for lung cancer patients are still bleak, but they have brightened for patients with breast, colon, and renal cancers, and lymphoma, she said.

This improvement could be seen in molecular imaging trials described in Orlando. A preliminary study involving 19 patients at Washington University in St. Louis, for example, suggested that FDG-PET may detect axillary breast cancer metastases that sentinel node lymphography missed in advanced cases. FDG-PET is not yet a sensitive test in the early stages of breast cancer, but it may be a good choice for detecting axillary disease among patients with lymphovascular invasion or large tumors.

New tracers are joining those in use with MRI and FDG-PET for assessing low-grade brain tumors, said Dr. Wei E. Chen, an assistant professor in the molecular and medical pharmacology department at the University of California, Los Angeles. FDG is well suited for monitoring anaplastic transformation, but amino acid uptake tracers such as methionine and F-DOPA are more effective for low-grade and recurrent tumors. They also outperform FDG for monitoring radiation necrosis and show promise for directing biopsy and monitoring treatment response.

Dr. Gunnar Blomquist, a senior scientist at Uppsala Academic Hospital in Finland, described results from the first study of fluorine-18 Pittsburgh compound B (PIB) to track amyloid deposition in the brains of Alzheimer's disease patients over time. Compared with normal controls, AD patients retain high amounts of PIB in their cerebral cortex, but repeat studies one-and-a-half to two-and-a-half years later found only minor changes in PIB uptake in AD patients. Results suggest hypothetically that amyloid deposition, detected with F-18 PIB, may precede changes in cognition and AD-related changes shown in FDG uptake.

In a plenary lecture, Dr. Ralph Weissleder, a professor of radiology at Harvard Medical School, described the design of nanoparticles as MR contrast media and injectable optical phosphor imaging as a gateway to in vivo cellular imaging at his Center for Molecular Imaging Research at Massachusetts General Hospital.

Nanoparticles have proved particularly useful for measuring angiogenic or cell surface targets. Weissleder's long-standing interest in proteases and its association with cardiovascular disease, cancer, asthma, and chronic obstructive pulmonary disease led to CMIR's development of protease-activated near-infrared probes that produce up to a 4200-fold increase in signal amplification compared with gadolinium contrast agents.

Myocardial stem cell research is in flux, with discoveries tumbling over one another in a race to develop therapies to regenerate heart muscle. Phase I trials of analogous skeletal myoblast transplantation showed improved left ventricular function but high incidence of ventricular arrhythmias, requiring implantable defibrillator placement in these patients. The source of arrhythmias was hypothesized to stem from a lack of electrical coupling between mature skeletal myoblasts and neighboring ventricular myocysts, according to cardiologist Dr. M. Roselle Abraham, an assistant professor of internal medicine at Johns Hopkins University.

Attention has shifted to the possibilities offered by cardiac stem cells, a new candidate for implantation. They were discovered three years ago in rats by Dr. Silvertri F. Beltrami of New York Medical College and were soon shown to be capable of regenerating heart muscles. Ex vivo cultures of cardiac stem cells grew in spherical clusters called cardiospheres. When cultured with rat ventricular myocytes, the combination produced what looked like little hearts in a dish. Human cardiac stem cells were isolated in 2005.

Imaging has been recognized as essential in the lab and clinic for treatment guidance and monitoring, but the best use of labeled nuclear, reporter genes, and MR imaging for these tasks has yet to be established. F-18 labeling appears to work well for tracking initial cell delivery but not for proliferation and survival studies because of short radioisotope half-life.

Reporter gene imaging has demonstrated efficacy in following the fate of cells and their progeny for up to 200 days and many cell generations, according to Dr. Joseph Wu, a clinical instructor of molecular imaging at Stanford University. A firefly lucerifase reporter gene technique used in a study presented at AMI showed value for identifying transplanted human stem cells that evolve into teratomas.

Simple magnetofection iron-oxide labeling offers researchers a more familiar and straightforward option with MRI. It was been used to monitor cell migration for up to eight weeks. While reporter gene imaging can detect as few as 1000 cells, however, an accumulation of at least 500,000 iron-labeled cells is needed for detection with 1.5T MRI.

The clinical ramifications of advanced molecular imaging are becoming apparent. University of British Columbia researchers discussed results of a mouse study suggesting that reporter gene imaging may be a good choice for monitoring transplanted pancreatic islet cells. Despite modest success with MRI and optical imaging, the fate of implanted islet cells remains largely a mystery for lack of a good in vivo test to monitor their status.

Christopher McIntosh, Ph.D., a professor of medicine and physiology at UBC, reported his group's success using HSV1-Sr39 TK reporter gene and F-18 FHBG probe technologies. In a mouse study, the microPET signal was directly proportional to the number of transplanted islets and sensitive enough to detect small changes in mass, he said. Islet cell graft survival in diabetic mice could be tracked for one month, and the resulting PET signal reflected the insulin production capacity of the transplanted cells.