We propose to develop a software package to automatically evaluate a subject's beta amyloid PET scan (using either C11-PIB, F18-florbetaben, or F18-florbetapir, F18-flutemetamol) by normalizing the subject's scan, masking away non-gray matter tissue (without relying on co-registered MRI scans), placing standardized ROIs onto the transverse slices, and reporting SUVr values in separate brain areas referenced to the cerebellar gray matter. Our goal is that this analysis package ultimately would be FDA-510(k) approved and distributed to hospitals and clinics (and pharmaceutical companies), as a commercial product, to aid in the evaluation and diagnosis of patients. Through the use of such a validated and standardized analysis package, new radio-tracers can be objectively compared for their accuracy in quantitating beta amyloid in the brain, and more importantly, new therapies can be objectively and quantitatively evaluated for their efficacy in preventing or removing beta amyloid for each patient, on a personalized individual basis. An important portion of the testing, user interface evaluation, and ADER's report generation utility and clinical application will be conducted in a subaward under the supervision of Dr. Michael Devous within the Nuclear Medicine Center at the UT Southwestern Medical Center, Dallas, Texas. At MNI, New Haven, we will continue to test and evaluate ADER in house within our Radio-tracer Evaluation Program (RTEP) program, where we continue to test potential new beta amyloid PET and SPECT imaging agents, while clinically evaluating subjects by our in-house neurologists and support staff. The potential benefit to society is considerable since an ADER analysis package would provide a quantitative biomarker analysis method for Alzheimer's disease progression for individualized therapy efficacy. Alzheimer's disease (AD) is associated with significant morbidity and a useful marker and/or brain scan analysis package, like this proposed ADER, would add to our understanding of AD disease progression and provide objective assessment of neuroprotective and restorative therapies. This fully automated image processing will also allow for fewer subjects to be studied (with the same clinical power) in clinical trials using new PET and SPECT radioligands. As new tracers and therapies are developed, ADER would co-evolve with these studies into an optimized image analysis method for diagnosing, staging and treating Alzheimer's disease.
Evaluation of Radiotracers (ADER) Project Narrative We propose to develop an automated package for analysis of beta-amyloid accumulation in Alzheimer's patients'brains which can be easily implemented by pharmaceutical companies for therapeutic drug discovery, as well as in a clinical setting, for high quality quantitative PET (and SPECT) imaging assessments. This analysis will remove subjectivity in the determination of the imaging outcome measure and permit a reproducible evaluation of new Alzheimer's radio- tracers'imaging potential. ADER can be used to test the efficacy of new Alzheimer's therapies in which FDA Phase II tested radiotracers are used as surrogate biomarkers. Our validated image processing package is highly relevant to the ongoing search for new diagnostics and treatments since it will serve as a new """"""""medical device"""""""" (as defined by the FDA), which will improve the way in which medical care is delivered to Alzheimer's patients.
