Evaluating atypical dementia syndromes using positron emission tomography with carbon 11 labeled Pittsburgh Compound B.

CONTEXT: A progressive decline in episodic memory affecting activities of daily living is the usual clinical presentation of Alzheimer disease. However, patients presenting with atypical or focal clinical symptoms such as language or visuospatial dysfunction often pose a diagnostic challenge. OBJECTIVE: To explore the presence and topography of beta amyloid (Abeta) as measured by carbon 11-labeled Pittsburgh Compound B ((11)C-PiB) in patients with atypical presentations of dementia. DESIGN, SETTING, AND PARTICIPANTS: At a tertiary referral center for memory disorders, 15 healthy controls, 10 patients with Alzheimer disease, a patient with primary progressive aphasia (PPA), and a patient with posterior cortical atrophy (PCA) underwent (11)C-PiB positron emission tomographic studies. Retention of (11)C-PiB was compared between different groups using statistical parametric mapping. MAIN OUTCOME MEASURE: The topography of cortical (11)C-PiB binding in atypical vs typical Alzheimer disease. RESULTS: Cortical (11)C-PiB binding was higher in the group with Alzheimer disease and in the patients with PPA and PCA than the controls (P < .001). Both patients with atypical dementia had a similar (11)C-PiB binding pattern to Alzheimer disease although (11)C-PiB retention was higher on the left cerebral hemisphere in the patient with PPA (P < .01) and higher in the occipital cortex in the patient with PCA (P < .01). CONCLUSIONS: The presence of distinctive focal (11)C-PiB retention patterns was demonstrated in 2 patients with atypical onset of dementia. Pittsburgh Compound B has the potential to facilitate differential diagnosis of dementia and identify patients who could benefit from specific therapeutic strategies aimed at beta amyloid reduction.

Poly(ortho esters): synthesis, characterization, properties and uses.

Over the last 30 years, poly(ortho esters) have evolved through four families, designated as POE I, POE II, POE III and POE IV. Of these, only POE IV has been shown to have all the necessary attributes to allow commercialization, and such efforts are currently underway. Dominant among these attributes is synthesis versatility that allows the facile and reproducible production of polymers having the desired mechanical and thermal properties as well as desired erosion rates and drug release rates that can be varied from a few days to many months. Further, the polymer is stable at room temperature when stored under anhydrous conditions and undergoes an erosion process confined predominantly to the surface layers. Important consequences of surface erosion are controlled and concomitant drug release as well as the maintenance of an essentially neutral pH in the interior of the matrix because acidic hydrolysis products diffuse away from the device. Two physical forms of such polymers are under development. One form, solid materials, can be fabricated into shapes such as wafers, strands, or microspheres. The other form are injectable semi-solid materials that allow drug incorporation by a simple mixing at room temperature and without the use of solvents. GMP toxicology studies on one family of POE IV polymers has been concluded, an IND filed and Phase I clinical trials are in progress. Important applications under development are treatment of post-surgical pain, osteoarthritis and ophthalmic diseases as well as the delivery of proteins, including DNA. Block copolymers of poly(ortho ester) and poly(ethylene glycol) have been prepared and their use as a matrix for drug delivery and as micelles, primarily for tumor targeting, are being explored.

Post surgical pain management with poly(ortho esters).

Poly(ortho esters), POE, are synthetic bioerodible polymers that can be prepared as solid materials, or as viscous, injectable polymers. These materials have evolved through a number of families, and the latest member of this family, POE IV, is particularly well suited to drug delivery since latent acid is integrated into the polymer backbone, thereby, modulating surface erosion. POE IV predominantly undergoes surface erosion and is able to moderate drug release over periods from days to many months. One indication in which the POE IV polymer is currently being investigated is in sustained post-surgical pain management. The local anesthetic agent, mepivacaine, has been incorporated into a viscous, injectable POE IV and its potential to provide longer-acting anesthesia has been explored in non-clinical models.