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FROM the LITERATURE PET in Assessment of Abuse Potential NEWSLINE FROM THE LITERATURE Each month the editor of Newsline drug radafaxine ([2S,3S])-2-[3-chlo- in the putamen. The authors con- selects articles on diagnostic, thera- rophenyl]-3,5,5,-trimethyl-2-mor- cluded that these and other data “sug- peutic, research, and practice issues pholinol hydrochloride). Radafaxine gest that the neurodegenerative from a range of international publica- is a potent metabolite of bupropion process in PD follows a negative ex- tions. Most selections come from out- that is being evaluated both as a treat- ponential course and slows down side the standard canon of nuclear ment for depression and for possible with increasing symptom duration, medicine and radiology journals. Note use in treatment of obesity. The study contradicting the long-latency hypo- that although we have divided the ar- included 8 healthy men who under- thesis of PD.” ticles into diagnostic and therapeutic went 11C-cocaine PET imaging at 1, Archives of Neurology categories, these lines are increasingly 4, 8, and 24 hours after radafaxine blurred as nuclear medicine capabili- administration. The authors found ties rapidly expand. Many diagnostic that DAT blockade by radafaxine PET and rCBF in Cocaine capabilities are now enlisted in direct was slow, reaching 11% at 1 hour Use Disorder support of and, often, in real-time con- and a peak blockade of 22% at 4 In an article e-published ahead of junction with, therapies. These briefs hours. The maximum blockade in print in the March 9 issue of the are offered as a monthly window on the any single subject was 33%. No ad- Journal of Cerebral Blood Flow and broad arena of medical and scientific verse effects were noted. They con- Metabolism, Johnson et al. from the endeavor in which nuclear medicine cluded that the relatively low potency University of Virginia (Charlottes- now plays an essential role. This 15 of radafaxine in blocking DAT, its ville) used H2 O PET in the investi- month, the literature yielded an unusu- slow pharmacokinetics, and its gation of cocaine’s dose-dependent, ally high number of articles on nuclear steady-state DAT blockade suggest time-related effects on regional cere- medicine techniques in neurologic and that radafaxine “is likely to have min- bral blood flow (rCBF) in 31 individ- psychiatric assessment applications. imal or no reinforcing potential and is uals with cocaine use disorder. therefore unlikely to be abused.” Participants were divided into 2 Diagnosis Biological Psychiatry groups administered (a) a low dose of cocaine or a placebo and (b) a high PET in Assessment of PET Sees Parkinson’s dose of cocaine or a placebo, with Abuse Potential Progression as Nonlinear testing of different dose conditions in the same individual separated by a In the March 15 issue of Biolog- Hilker et al. from the University period of at least 48 hours. At each ical Psychiatry (2005;57:640–646), of Cologne (Germany) reported in test, individuals underwent H15O researchers from the Brookhaven Na- the March issue of the Archives of 2 PET to assess rCBF. Global and re- tional Laboratory (Upton, NY) and Neurology (2005;62:378–382) on a gional hypoperfusion were associated the State University of New York at study using 18F-fluorodopa PET to with both low- and high-dose cocaine Stony Brook reported on a novel use determine the progression of striatal conditions but not with placebo ad- of PET to predict abuse potential for dopaminergic impairment in patients a new antidepressant based on dopa- with Parkinson’s disease (PD). The ministration. The hypoperfusion ef- mine transporter (DAT) occupancy. study included 31 individuals with a fects of cocaine peaked at 8 minutes. Volkow et al. in previous studies wide range of PD symptom duration The authors noted that although have described the use of PET in and severity and also included a cocaine-induced hypoperfusion oc- assessing possible reinforcing effects group of healthy controls. Baseline curred throughout the brain, the left of DAT-blocking drugs. These stud- 18F-fluorodopa PET imaging was fol- hemispheric dopamine-rich sublobar ies have shown that such drugs must lowed up for periods averaging 64.5 region was the most severely af- block more than 50% of DAT within months. In patients with PD, the rate fected. They concluded that increas- a relatively short period of time (Ͻ15 of decline in the putamen 18F-fluoro- ingly larger doses of cocaine may be minutes after administration) to pro- dopa uptake constant correlated in- associated with greater risk for ische- duce reinforcing effects. In the cur- versely with disease duration before mic stroke, particularly in this area of rent study, they assessed the potency entering the study. Annual disease the brain. and pharmokinetics of DAT blockade progression rates ranged from 4.4% Journal of Cerebral Blood Flow induced by the new antidepressant in the caudate nucleus to 6.3% and Metabolism Newsline 33N PET and Effects of and hippocampus in the verbal work- diffuse gliomas on MR imaging, Smoking ing memory task, suggesting in- 18F-FET PET and MR spectroscopy In an article published in the creased dopamine releases in these analyses markedly improved the di- March issue of the American Journal areas. Their results also indicated agnostic efficacy of targeted biop- of Psychiatry (2005;162:567–577), that, in the working memory task, sies.” NEWSLINE Zubieta et al. from the University of increased dopamine release in the Journal of Neurosurgery Michigan (Ann Arbor) reported on right ventrolateral frontal cortex was the effects of cigarette smoking on associated with faster performance 18 and that increased dopamine release F-FDOPA PET and the regional cerebral blood flow (rCBF). Effects of Aging The study included 19 tobacco smok- in the left ventral anterior cingulate In an article e-published ahead of ers who were studied with 15O-water was associated with more consistent print on February 23 in the Journal of PET after overnight abstinence. A performance. They concluded that Cerebral Blood Flow and Metabo- baseline scan was obtained, and each these “results indicate that regionally lism, Kumakura et al. from the Aar- individual was scanned before and af- specific components of the fronto- hus University Hospitals and the ter smoking 3 consecutive cigarettes. temporal dopaminergic network are Centre for Functionally Integrated Participants were also surveyed for functionally involved in working Neuroscience (Aarhus, Denmark) re- subjective feelings of nicotine craving. memory performance in humans.” ported on a study of potential biasing The researchers found that smoking the Journal of Neuroscience effects in the current use of 18F- first cigarette of the day resulted in fluorodopa (18F-FDOPA) PET to study increases in rCBF in the visual cortex 18 F-FET PET Enhances age-related changes in dopamine re- and cerebellum and reductions in the MR Spectroscopy in lease and transport. The authors ap- anterior cingulate, right hippocampus, plied a constrained compartmental and ventral striatum. Cigarette craving Gliomas analysis to calculate the imaged brain scores correlated with some but not all Floeth et al. from the Heinrich- concentrations of the plasma metabo- of these rCBF changes. Subsequent Heine University (Dusseldorf, Ger- lite 3-O-methyl-FDOPA during 120 cigarettes had similar but reduced ef- many) reported in the February issue 18 fects. The authors noted that these PET of the Journal of Neurosurgery minutes of F-FDOPA circulation in 3 data indicate that smoking affects (2005;102:318–327) on a study de- groups of participants: healthy young rCBF in areas implicated in the reward- signed to determine the predictive and healthy elderly individuals and in- 18 ing effects of drugs of abuse and that value of F-fluoroethyl-L-tyrosine dividuals with Parkinson’s disease. A 18 areas associated with cigarette craving ( F-FET) PET and MR spectroscopy global negative bias was found in con- 18 match those previously associated with for tumor diagnosis in patients with ventional estimates of F-FDOPA drug craving and relapse to drug- suspected gliomas. The study in- clearance when compared with those seeking behavior. cluded 50 patients with newly diag- derived from the novel analysis. In ad- American Journal of Psychiatry nosed intracerebral lesions diagnosed dition, the effective distribution vol- as diffuse gliomas by contrast- ume for 18F-FDOPA, an index of do- enhanced MR. 18F-FET PET and MR pamine storage capacity in brain, was Dopamine and Working spectroscopy analyses were per- reduced by 85% in the putamen of pa- Memory formed on each patient. PET was tients with PD and 58% in healthy el- Aalto et al. from the University of considered positive with lesion-to- derly participants when compared with Turku (Finland) reported in the brain ratios of uptake Ͼ1.6. MR healthy young participants. This indi- March issue of the Journal of Neuro- spectroscopy was considered positive cates that the storage capacity for do- science (2005;25:2471–2477) on the when N-acetylaspartate was de- pamine in both caudate and putamen in use of PET and a high-affinity dopa- creased in conjunction with an abso- patients with PD is more profoundly mine D2 receptor in the study of lute increase of choline, with a ratio impaired than is the capacity for 18F- working memory function in healthy of the previous to the latter Յ0.7. FDOPA utilization as routinely calcu- humans. The study included 12 vol- These PET and MR ratios were com- lated by conventional net influx plots. unteers who underwent 11C-FLB-457 pared with biopsy findings and were The authors added that these results PET imaging while performing ver- significant independent predictors for “constitute the first demonstration of an bal working memory and sustained correct identification of tumor tissue. abnormality in the cerebral utilization attention tasks.
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