Differences in [99mTc]TRODAT-1 SPECT binding to dopamine transporters in patients with multiple system atrophy and Parkinson's disease.

PURPOSE: Multiple system atrophy (MSA), a disorder causing autonomic dysfunction, parkinsonism, and cerebellar dysfunction, is difficult to differentiate from other movement disorders, particularly early in the course of disease. This study evaluated whether [99mTc]TRODAT-1 binding to the dopamine transporter differentiates MSA from other movement disorders. METHODS: Single-photon emission computed tomographic brain scans were acquired in 25 MSA patients, 48 age-matched controls, and 130 PD patients, 3 h after the injection of 740 MBq (20 mCi) of [99mTc]TRODAT-1. Regions of interest (ROIs) were placed manually on subregions of both basal ganglia and distribution volume ratios (DVRs) were calculated. Regional DVRs were compared between study groups in MSA patients. Student's t tests were used to compare MSA patients with other study groups. Spearman correlations were used to compare DVRs with NP measures. RESULTS: Based upon various motor scores, MSA and PD patients had comparable motor impairment, and were significantly impaired compared with controls. Mean DVRs in the basal ganglia of MSA patients were significantly less than those of controls, but generally higher (p<0.05) than in PD patients. In particular, the MSA patients had significantly increased DVRs in the posterior putamen (mean 0.49+/-0.30) compared with PD patients (0.74+/-0.25). CONCLUSION: Movement disorder patients could be differentiated from controls, but MSA and PD patients could not be easily differentiated from each other. As a group, MSA patients had significantly higher mean [99mTc]TRODAT-1 binding, particularly in the posterior putamen, compared with PD patients and significantly lower binding compared with controls. This may reflect different pathophysiological processes of the two neurodegenerative diseases.

Biodistribution and imaging with (123)I-ADAM: a serotonin transporter imaging agent.

UNLABELLED: 2-((2-((Dimethylamino)methyl)phenyl)thio)-5-(123)I-iodophenylamine ((123)I-ADAM) is a new radiopharmaceutical that selectively binds the central nervous system serotonin transporters. The purpose of this study was to measure its whole-body biokinetics and estimate its radiation dosimetry in healthy human volunteers. The study was conducted within a regulatory framework that required its pharmacologic safety to be assessed simultaneously. METHODS: The sample included 7 subjects ranging in age from 22 to 54 y old. An average of 12.7 whole-body scans were acquired sequentially on a dual-head camera for up to 50 h after the intravenous administration of 185 MBq (5 mCi) (123)I-ADAM. The fraction of the administered dose in 13 regions of interest (ROIs) was quantified from the attenuation-corrected geometric mean counts in conjugate views. Multiexponential functions were iteratively fit to each time-activity curve using a nonlinear, least-squares regression algorithm. These curves were numerically integrated to yield source organ residence times. Gender-specific radiation doses were then estimated with the MIRD technique. SPECT brain scans obtained 3 h after injection were evaluated using an ROI analysis to determine the range of values for the region to cerebellum. RESULTS: There were no pharmacologic effects of the radiotracer on any of the subjects, including no change in heart rate, blood pressure, or laboratory results. Early planar images showed differentially increased activity in the lungs. SPECT images demonstrated that the radiopharmaceutical localized in the midbrain in a distribution that is consistent with selective transporter binding. The dose-limiting organ in both men and women was the distal colon, which received an average of 0.12 mGy/MBq (0.43 rad/mCi) (range, 0.098-0.15 mGy/MBq). The effective dose equivalent and effective dose for (123)I-ADAM were 0.037 +/- 0.003 mSv/MBq and 0.036 +/- 0.003 mSv/MBq, respectively. The mean adult male value of effective dose for (123)I-ADAM is similar in magnitude to that of (111)In-diethylenetriaminepentaacetic acid (0.035 mGy/MBq), half that of (111)In-pentetreotide (0.81 mGy/MBq), and approximately twice that of (123)I-inosine 5'-monophosphate (0.018 mGy/MBq). The differences in results between this study and a previous publication are most likely due to several factors, the most prominent being this dataset used attenuation correction of the scintigraphic data. Region-to-cerebellum ratios for the brain SPECT scans were 1.95 +/- 0.13 for the midbrain, 1.27 +/- 0.10 for the medial temporal regions, and 1.11 +/- 0.07 for the striatum. CONCLUSION: (123)I-ADAM may be a safe and effective radiotracer for imaging serotonin transporters in the brain and the body.

A metabolic imaging severity rating scale for the assessment of cognitive impairment.

PURPOSE: This study was designed to validate a simple scoring system for evaluating fluorodeoxyglucose (FDG) positron emission tomographic (PET) scans that can be used routinely in patients undergoing the clinical assessment of cognitive impairment. METHODS: The FDG-PET scans of 106 patients with cognitive impairment (65 with Alzheimer disease, 16 with frontal lobe dementia, and 25 atypical cases) were acquired using the PENN-PET scanner 40 minutes after the intravenous administration of 8 mCi FDG. Metabolic activity in various anatomic structures of the brain was scored using the following qualitative scale: 4 = normal; 3 = mildly decreased; 2 = moderately decreased; 1 = severely decreased; and 0 = no activity. Regions of interest were also placed over these regions to obtain a quantitative value. Two distinct scores were obtained. Values for visual and sensorimotor cortices, thalami, basal ganglia, and cerebellum comprised score I. Score II consisted of the values for the frontal, temporal, and parietal cortices. The qualitative metabolic imaging severity rating scale (MISRS) was compared with a quantitative MISRS (obtained from the region-of-interest analysis of the same structures). The MISRS was then compared with the results from the Mini-Mental Status Examination (MMSE) and the Dementia Severity Rating Score (DSRS). RESULTS: In all patients, the qualitative MISRS scores correlated significantly with the quantitative MISRS (r = 0.73, P < 0.0001). In all patients with cognitive impairment, the qualitative and quantitative MISRS scores correlated significantly with the DSRS and the MMSE (P < 0.001). In patients with Alzheimer disease, the qualitative and quantitative MISRS significantly correlated with the DSRS and MMSE. CONCLUSION: A simple and practical rating scale can be used to assess the severity of cognitive impairment in patients with different types of dementing illnesses.