"We have demonstrated that the worsening of memory and other cognitive functions is correlated with the increase of 18F-FDDNP brain binding in a progressive pattern closely matching the known pattern of pathology progression," explained Vladimir Kepe, assistant researcher at the David Geffen School of Medicine at the University of California, Los Angeles. "Our method is sensitive to detect the regional increases in pathology (or the nature of the disease) as well as spreading of pathology within the brain of the same person as the disease worsens over time," added the co-author of "Detection of MCI-AD and Control-MCI Conversions in Alzheimer's Disease Patients With [F-18]FDDNP PET."
Alzheimer's is the most common form of dementia among older people; it is a progressive, irreversible brain disorder with no known cause or cure. More than 4.5 million Americans suffer from Alzheimer's and its symptoms of memory loss, confusion, impaired judgment, personality changes, disorientation and loss of language skills. Alzheimer's disease is marked by progressive deterioration of memory and other cognitive functions (attention, language, reasoning, etc.) due to the cell loss in the vulnerable neuronal populations, which form brain circuitry responsible for these cognitive functions, said Kepe. In clinical settings, Alzheimer's disease is diagnosed based on performance in a variety of tests examining memory loss, language skills and other cognitive functions, but these tests offer only diagnosis of probable Alzheimer's disease, he said. For a definite diagnosis, a brain autopsy is necessary to detect the presence of brain lesions: neurofibrillary tangles and beta-amyloid plaques.
For nearly a decade, UCLA researchers under the leadership of Jorge R. Barrio and Gary W. Small have been investigating techniques to detect and measure the levels of both types of lesions in the brains of living Alzheimer's patients using PET and the radiotracer 18F-FDDNP, a molecular imaging probe that binds to the neurofibrillary tangles and beta-amyloid plaques. "18F-FDDNP was the first molecular imaging probe successfully used for imaging of neuropathological lesions in Alzheimer's disease patients with PET," noted Kepe. Combined with the results of PET studies using FDG, a radiotracer commonly used to measure decrease in brain metabolic activity caused by Alzheimer's, it provides valuable information about disease status. With 18F-FDDNP PET, scientists "can detect the presence of these lesions in different brain regions and measure their relative regional density," he said. "Because the lesions appear first in the medial temporal lobe and then slowly spread to the rest of the brain as the disease progresses, we can detect the extent of this spread and use 18F-FDDNP as an indicator of the disease progression," added the UCLA researcher.
"This study brings us one step closer to using 18F-FDDNP PET in the clinical setting for the diagnosis of Alzheimer's," said Kepe, continuing, "The fact that the method can detect changes in pathology caused by the disease progression is very significant, it demonstrates the method's sensitivity."
The UCLA researchers performed a large imaging study of neurodegeneration in 60 individuals (including healthy subjects, individuals with Alzheimer's and individuals with mild cognitive impairment). "The F18-FDDNP signal in all analyzed areas (medial temporal, lateral temporal, parietal, frontal and posterior cingulate gyrus) was significantly higher in the Alzheimer's patients than in the control group," said Kepe. Individuals with mild cognitive impairment "displayed a more limited pattern of 18F-FDDNP distribution (medial temporal, lateral temporal, posterior cingulate gyrus), with several people who displayed a low level of F18-FDDNP signal," he added.
Abstract: V. Kepe, G.W. Small, L.M. Ercoli, P. Siddarth, H.V. Vinters, N. Satyamurthy, S. Huang, M.E. Phelps and J.R. Barrio, all at David Geffen School of Medicine at UCLA, Los Angeles, Calif., and G.M. Cole, VA Medical Center, Sepulveda, Calif., "Detection of MCI-AD and Control-MCI Conversions in Alzheimer's Disease Patients With [F-18]FDDNP PET," SNM's 53rd Annual Meeting, June 3–7, 2006, Scientific Paper 208.
About SNM
SNM is holding its 53rd Annual Meeting June 3–7 at the San Diego Convention Center. Research topics for the 2006 meeting include molecular imaging in clinical practice in the fight against cancer; the role of diagnostic imaging in the management of metastatic bone disease; metabolic imaging for heart disease; neuroendocrine and brain imaging; new agents for imaging infection and inflammation; and an examination of dementia, neurodegeneration, movement disorders and thyroid cancer.
SNM is an international scientific and professional organization of more than 16,000 members dedicated to promoting the science, technology and practical applications of molecular and nuclear imaging to diagnose, manage and treat diseases in women, men and children. Founded more than 50 years ago, SNM continues to provide essential resources for health care practitioners and patients; publish the most prominent peer-reviewed resource in the field; sponsor research grants, fellowships and awards; host the premier annual meeting for medical imaging; and train physicians, technologists, scientists, physicists, chemists and radiopharmacists in state-of-the-art imaging procedures and advances. SNM members have introduced--and continue to explore--biological and technological innovations in medicine that noninvasively investigate the molecular basis of diseases, benefiting countless generations of patients. SNM is based in Reston, Va.; additional information can be found online at http://www.snm.org.