PET Imaging Plays Key Role in Supporting Parkinson’s Disease Research
A large-scale study conducted to gauge the effectiveness of dopamine cell transplantation in Parkinson’s disease patients revealed significant improvements in motor skills and brain function.
The results of this study, reported in the January 2010 issue of The Journal of Nuclear Medicine (JNM), demonstrated that transplanted cells were viable and integrated well with the host brain tissue. Furthermore, these cells produced dopamine that helped support the brain and led to an improvement in motor symptoms. These improvements were sustained over a four-year study period.
“This study provided new insights into the time course of transplantation outcome,” said David Eidelberg, M.D., study coauthor and director of the Neuroscience Center at the Feinstein Institute for Medical Research (Manhasset, NY, USA). “Comprehensive long-term clinical follow-up, together with molecular imaging, allows for a more realistic appraisal of this kind of intervention for Parkinson’s disease.”
Researchers reported long-term clinical and imaging outcomes after transplantation from 33 patients who originally participated in a one-year, double-blind, placebo-controlled trial of embryonic dopaminergic cell implantation for Parkinson’s disease. Clinical improvement in motor ratings, as well as increased brain uptake of 18F-fluorodopa (18F-FDOPA)--the radiotracer that is extensively used to investigate the function of dopamine grafts--was evident at one, two and four years after the transplantation surgery.
The findings reported in this study demonstrate the critical roles played by positron emission tomography (PET)--a noninvasive molecular imaging technique--in screening patients for transplantation procedures and in objectively assessing graft survival over the long term. “This work provides a valuable template for conducting imaging-based trials of cell transplantation for Parkinson’s disease and perhaps other neurodegenerative disorders,” said Yilong Ma, Ph.D., lead author of the JNM study and associate investigator at the Feinstein Institute for Medical Research. “It offers guidance in the design of this type of trial, particularly with respect to the use of quantitative imaging as an adjunct to clinical assessments.”
According to the U.S. National Institute of Neurological Disorder and Stroke (Bethesda, MD, USA), Parkinson’s disease belongs to a group of conditions called motor system disorders, which are the result of the loss of dopamine-producing brain cells. The four primary symptoms are tremor--or trembling in hands, arms, legs, jaw and face; rigidity--stiffness of the limbs and trunk; bradykinesia--slowness of movement; and/or postural instability--impaired balance and coordination.
Parkinson’s disease typically affects people over the age of 50. Early symptoms are subtle and occur gradually. In some people, the disease progresses more quickly than in others. Parkinson’s disease is both chronic and progressive. There is presently no cure; however, a host of medications provide dramatic relief from the symptoms. Innovative surgical interventions such as cell transplantation and gene therapy are currently being investigated for patients with medically refractory symptoms.
17. December 2009
Scientists from the Kimmel Cancer Center at Jefferson have discovered a possible way for malignant breast tumors to be identified, without the need for a biopsy. The findings were published online ahead of print in the Journal of Nuclear Medicine.
Current imaging modalities miss up to 30% of breast cancers and cannot distinguish malignant tumors from benign tumors, thus requiring invasive biopsies. Approximately 5.6 million biopsies performed in the United States find only benign lesions. These biopsies cause substantial stress for the patients and have significantly high costs.
"The challenge has been to develop an imaging agent that will target a specific, fingerprint biomarker that visualizes malignant breast lesions early and reliably," said Mathew Thakur, Ph.D., professor of Radiology at Jefferson Medical College of Thomas Jefferson University and director of Radiopharmaceutical Research and Nuclear Medicine Research.
Dr. Thakur and colleagues studied an agent called 64Cu-TP3805, which is used to evaluate tumors via PET imaging. 64Cu-TP3805 detects breast cancer by finding a biomarker called VPAC1, which is overexpressed as the tumor develops.
The researchers compared the images using that agent with images using the "gold standard" imaging agent, 18F-FDG. They used MMTVneu mice, which are mice that develop breast tumors spontaneously, like humans. The mice first received a PET scan using the 18F-FDG. Then they received a CT scan, and then they received another PET scan using 64Cu-TP3805.
Ten tumors were detected on the mice. Four tumors were detected using both 18F-FDG and 64Cu-TP3805, and four additional tumors were found with 64Cu-TP3805 only. All eight of these tumors overexpressed the VPAC1 oncogene on tumor cells and were malignant by histology. The remaining two tumors were benign and were detected only with 18F-FDG. They did not express the VPAC1 oncogene, and thus were not detected by the 64Cu-TP3805.
"If this ability of 64Cu-TP3805 holds up in humans, then in the future, PET scans with 64Cu-TP3805 will significantly contribute to the management of breast cancer," Dr. Thakur said.