Faculty Bibliography

[I-123]5-I-A-85380 ([I-123]5-IA) is a ligand specific for the alpha4beta2 nicotinic acetylcholine receptor (nAChR) subtype. It was reported that distribution volume (DV) is an appropriate measurement for alpha4beta2 nAChR density in baboon [I-123]5-IA dynamic SPECT studies. To evaluate the kinetics obtained from human [I-123]5-IA dynamic SPECT, three different methods were applied to region of interest (ROI) kinetics analysis as folows: A: a 2-compartment 3-parameters model, B: 3-compartment 5-parameter model, and C: same model as in B but fitting with a constraint of ratio of K-1/k(2)e stimated by fitting occipital kinetics to model in A. The DV was estimated as DV = K-1/k(2) for A, and DV=(K-1/k(2))(1+k(3)/k(4)) for B and C. Nonlinear least squares fitting using Marquardt algorithm was performed for A-C. Akaike information criterion (AIC) and R-2 were used for evaluation of fitting results. A linear parametric imaging algorithm derived from model in method A was used for generating images of K, and DV. Four normal human [I-123]5-IA dynamic studies were evaluated by A-C. In each study, after a bolus of [I-123]5-IA (5similar to10 mCi, specific activity>10 Ci/umol) was injected intravenously, a dynamic scanning with 20 acquistions over 6 hour was started immediately on a Trionix TriadXLT scanner. 30-40 arterial plasma samples were taken during the study and HPLC was performed to determine the metabolite-corrected arterial plasma radioactivity as input function. The ROI regions (cerebellum, frontal cortex, occipital cortex, pones, and thalamus) were drawn on co-registered MRI images. Results show that A fits to all ROI kinetics very well (R-2>0.99), and paired T-test for AIC showed there is no statistical significantly improvement of model fitting from B, C methods The K-1 and DV images are of good image quality. Conclusion: A is best for ROI kinetic analysis and parametric imaging for DV and K-1.

Published 1/16/2002. The representation in multiple media of the expressions of a creative senior citizen with mood and personality disorders is valuable for clinical, research, and teaching purposes. The purpose of this article was to document the occurrence of likely bipolar II and histrionic personality disorders in a creative senior citizen utilizing oral and written testimony and drawings by the subject herself. The author, a close friend of the subject during her final two decades, examined posthumously her memoirs, notes, letters, drawings, photographs, and related materials to produce a psychological record of her life illustrating expressions of sadness, loss, originality, excessive emotionality, and attention seeking. Oral monologues, written notes, and drawings by the subject document the presence of likely bipolar II and histrionic personality disorders in an artistic senior citizen. The occurrence of likely bipolar II and histrionic personality disorders in a senior citizen is confirmed by means of the creative works of the subject in multiple media. This article demonstrates the value of the posthumous synthesis of the extant works of individuals exploiting the technical capabilities of a publication on the Internet to reproduce sounds and images.

Reduction of alpha 4beta 2 nAChRs is implicated in Alzheimer (AD) cognitive decline. Besides their AChE properties, galantamine (GAL) and physostigmine (Phys) bind to nAChR sites distinct from the ACh-binding site and may allosterically potentiate nACh agonist binding (APL).We developed (S)-5 Iodo 1 2 3I-3-(2-azetidinylmethoxy) pyridine (5-IA) and have previously applied it to 10 humans with regional nAChR quantification by math modeling. Gal and Phys effects on 5-IA nAChR binding were examined with chronic dosing in mice. Isotopic 1 1CGal was synthesized (333GBq/mumole yield 10%) following 1 1C methylation, DMS at 80degreeC 5 minutes and studied in mice (5-60 min) and baboons (90 min.). 7 days of GAL (0.25 and 1 mg/kg s.c. per day) showed upregulation of 1 2 5I 5-IA binding in mouse cortex (cx) and hippocampus (p <0.05), and in thalamus (T) and superior colliculus (SC) (trend). 2 week GAL in mice of 0.3, 3 and 5 mg/kg/d sc and Phys, 0.5 mg/kg/d IP were carried out. Sacrifice on day 15, 30 min. pi on day 15 showed significant elevation of binding with 18F A-85380 and 5-IA in the Phys mice in T, occipital, parietal (p<0.05). 1 1CGal mice studies at high (1 mug/kg)/low specific activity (1 mg/kg) showed 15% blockade (T and SC at 30 min). Dynamic baboon PET (0.02 mug/kg) showed high brain uptake of 1 1CGal apprx4% ID/g at 5 min p.i.) and rapid dissociation (T1/2apprx25 min), with frontal >T>striatum>cerebellum. A 1-tissue compartment model was preferred over a 2-tissue one. Distribution volume ranged 3.53-2.51 ml/ml (S>T) cx>pons>T>CB). Imaging of nAChR elucidates mechanism and dosing of APLs for AD treatment