NEWSLINE

FROM THE LITERATURE

Each month the editor of Newsline 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 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- 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 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 . These stud- 18F-fluorodopa PET imaging was fol- hemispheric -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 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 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 , 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. The authors noted re- Accuracy in such identification could of 18F-FDOPA in caudate and putamen duced D2 receptor availability in the be increased from 68% with the use as a function of normal aging, which left ventral anterior cingulate in both of MR imaging alone to 97% with the we attribute to loss of vesicular storage tasks and reduced D2 receptor avail- addition of 18F-FET PET. The au- capacity.” ability in the ventrolateral frontal cor- thors concluded that “in patients with Journal of Cerebral Blood Flow tex bilaterally and in the amygdala intracerebral lesions supposed to be and Metabolism

34N THE JOURNAL OF NUCLEAR MEDICINE • Vol. 46 • No. 5 • May 2005 NEWSLINE

123I-␤-CIT SPECT and functional class II or III heart failure 15-3 and number of metastases, we Serotonin Transporters and 18 healthy elderly volunteers. consider scintigraphy an appropriate 99m In an article e-published ahead of Each underwent Tc-HMPAO im- method for assessment of bone me- print on March 16 in Neuropsycho- aging. The researchers found signifi- tastases in breast cancer.” pharmacology, de Win et al from the cant rCBF reductions in 2 main foci Bosnian Journal of Basic Medical University of Amsterdam (The in patients with heart failure: the left Sciences Netherlands) reported on a study and right precuneus and cuneus and validating the use of 123I-␤-carbo- the right lateral temporoparietal cor- Immuno-PET with 124I- methoxy-3␤(4-iodophenyl) tex and posterior cingulate gyrus. Labeled Antibody They also identified a significant cor- (123I-␤-CIT) SPECT to assess 5-HT Robinson et al. from the Fox relation between the assessed degree serotonin transporters (SERTS) in Chase Cancer Center (Philadelphia, of cognitive impairment in these humans. Although 123I-␤-CIT has PA) reported in the February 15 issue patients and rCBF reductions. The shown promise in imaging of psy- of Cancer Research (2005;65:1471– authors concluded that, “these pre- chiatric diseases by binding in 1478) on a study investigating the liminary findings indicate that poste- SERT-rich areas of the brain, the au- potential for engineered antibody rior cortical areas of the brain may be thors sought to verify that the tech- fragments in the development of particularly vulnerable to brain per- nique could be useful in SERT-low novel PET tracers based on expres- fusion reductions associated with cortical areas. The study included 6 sion of tumor-associated antigens. heart failure and suggest that func- healthy men who underwent 2 123I-␤- The study focused on a small engi- tional deficits in these regions might CIT SPECT scans, 1 after pretreatment neered 124I-labeled antibody fragment be relevant to the pathophysiology of with the selective 5-HT inhib- specific for the HER2 receptor ty- the cognitive impairments” presented itor and another after ad- rosine kinase (C6.5 diabody). Work- by these patients. ministration of a placebo. Citalopram ing with mouse tumor xenografts, the Journal of Neuroimaging was found to reduce 123I-␤-CIT bind- authors found a time-dependent in- ing ratios in SERT-rich midbrain and crease in tumor-to-background signal hypothalamus and also (but at much Bone Scintigraphy and over the course of the experiments. less easily measured levels) in SERT- Marker Levels in Breast As part of the experiment, they also low cortical areas. Citalopram also in- Cancer validated a method for using a clini- creased binding ratios in the dopamine cal PET/CT scanner to quantify tu- Begic et al. from the University transporter-rich striatum and increased mor uptake in small-animal model Clinic Center in Sarajevo (Bosnia absolute uptake in the cerebellum. The systems. Using this system and the and Herzegovina) reported in the authors concluded that “The results HER2-dependent imaging, quantita- February issue of the Bosnian Jour- show that 123I-␤-CIT SPECT is a valid tion of tumor targeting by PET corre- nal of Basic Medical Sciences (2005; technique to study SERT binding in lated with traditional necropsy-based 5:23–26) on a study designed to cor- vivo in human brain in SERT-rich ar- analysis at all time points analyzed. relate levels of the tumor marker Ca eas” and that the use of this technique They concluded that “diabodies may 15-3 with indications of bone metas- may be valid in SERT-low areas but represent an effective molecular struc- tases on bone scintigraphy in women that such measurements must be inter- ture for development of novel PET ra- with breast cancer. The study in- preted with caution. diotracers.” cluded 25 women with breast cancer Neuropsychopharmacology Cancer Research who had previously undergone surgi- cal treatment. All patients underwent 99m 99m Tc-HMPAO SPECT and whole-body scintigraphy, and Ca Gated Tc-MIBI SPECT rCBF in Heart Failure 15-3 levels were measured. Bone and Regional EF Alves et al. from the University scintigraphy showed bone metastases In the March issue of Chest (2005; of Sao Paulo Medical School (Brazil) in 16 (64%) patients. Elevated Ca 127:778–786), Lapeyre et al. from the reported in the April issue of the 15-3 levels were seen in 11 (44%) Mayo Clinic and Mayo Foundation Journal of Neuroimaging (2005;15: patients with metastases and 1 patient (Rochester, MN) reported on a study 150–156) on a study using 99mTc- (4%) with no metastases noted on designed to evaluate a technique for hexamethylpropyleneamine oxime scintigraphy. Significant differences quantitative regional wall motion as- (99mTc-HMPAO) SPECT to assess in Ca 15-3 levels were found in pa- sessment using gated 99mTc-sestamibi the presence of resting regional cere- tients with metastases on scintigra- SPECT. The study included 14 healthy bral blood flow (rCBF) abnormalities phy compared with patients with no individuals and 25 patients who had in patients with heart failure. The metastases. The authors concluded experienced myocardial infarction study included 17 patients diagnosed that because “no significant correla- (MI). All patients underwent gated to be in New York Heart Association tion was found between level of Ca 99mTc-sestamibi SPECT imaging, with

Newsline 35N gated short-axis slice reconstruction tivity increased to 82% in the mild 83%, with 40% for 18F-FDG PET and and identification of endocardial bor- subgroup and 92% in the moderate- 123I-BMIPP SPECT, and 49% for 18F- ders. Regional ejection fraction (EF) to-severe subgroup. The authors con- FDG PET and 99mTc-tetrafosmin and myocardial perfusion were deter- cluded that “the ability to detect a SPECT. The accuracy of the combi- mined for 5 regions within each of 5 wall motion abnormality immedi- nation of 123I-BMIPP and 99mTc-

NEWSLINE selected slices in each study. Ten pa- ately after exercise gives incremental tetrafosmin SPECT imaging in tients also underwent echocardio- diagnostic value to myocardial perfu- predicting functional improvement graphic (ECG) regional wall-motion sion SPECT in the identification of was 70%, that of 18F-FDG PET and studies, with results compared with mild, single-vessel CAD.” 123I-BMIPP SPECT was 71%, and corresponding SPECT slice results. Circulation Journal that of 18F-FDG PET and 99mTc- Results indicated high interobserver re- tetrafosmin SPECT was 63%. The authors concluded that the combina- producibility in the assessment of re- Predicting Recovery After gional EFs. Regional EFs correlated tion of 123I-BMIPP and 99mTc- significantly with regional perfusion in Acute Myocardial tetrafosmin SPECT imaging is a anterior walls, lateral walls, and infe- Infarction practical modality for predicting the rior walls. Significant associations be- Seki et al. from Gunma Univer- functional improvement of ischemic tween the regional EFs and ECG sity (Maebashi, Japan) reported in the myocardium after a large acute myo- regional wall motion assessment were March issue of Circulation Journal cardial infarction. found at the base, midventricle, and (2005;69:311–319) on a study com- Circulation Journal apex. The authors concluded that, paring the abilities of combinations 99m 123 ␤ “gated SPECT images obtained with of Tc-tetrofosmin and I- - Therapy 99mTc-sestamibi can provide reproduc- methyliodophenyl pentadecanoic acid (BMIPP) SPECT, 18F-FDG PET ible quantitative, segmental regional 131 EFs for multiple left ventricular slices and 123I-BMIPP SPECT, and 18F- I-Labeled Chimeric that are significantly associated with FDG PET and 99mTc-tetrafosmin Tumor Necrosis RIT subjective regional wall motion assess- SPECT in predicting functional im- In the March 1 issue of the Jour- ment by echocardiography.” provement of ischemic myocardium nal of Clinical Oncology (2005;23: Chest after a large acute myocardial infarc- 1538–1547), Chen et al. from Fudan tion. The study included 10 patients University (Shanghai, China) re- who had experienced large acute ported on a study investigating the Dual-Isotope ECG-Gated myocardial infarction within the past therapeutic efficacy and toxicity of SPECT and Mild CAD 3 weeks. Each patient underwent 131I-labeled chimeric tumor necrosis Yoda et al. from the Nihon Uni- 99mTc-tetrasfosmin SPECT, 123I- radioimmunotherapy (RIT) in pa- versity School of Medicine (Tokyo, BMIPP SPECT, and 18F-FDG PET tients with advanced lung cancer. Japan) reported in the March issue of imaging. At 6-month follow-up, all Tumor necrosis treatment uses de- Circulation Journal (2005;69:301– patients had undergone successful re- generating tumor cells and necrotic 305) on a study to determine whether vascularization with no restenosis, regions of tumors as RIT targets. The myocardial perfusion SPECT is use- and follow-up 99mTc-tetrafosmin multiinstitutional study included 107 ful in the diagnosis of mild, single- SPECT imaging was performed. Re- patients with advanced lung cancer vessel coronary artery disease (CAD). searchers scored regional tracer up- who had experienced previous treat- The study included 97 individuals with take in each of the study images, ment failure after a median of 3 ra- a low likelihood of CAD and 46 pa- determined matches and mismatches, dio- or chemotherapy regimens. All tients with single-vessel CAD, each of and used quantitative gated SPECT patients underwent systemic or intra- whom underwent separate acquisition, to score wall motion. When the rela- tumoral injection of 131I-chimeric tu- dual-isotope electrocardiograph-gated tive abilities of combinations of im- mor necrosis antibody. Results exercise SPECT. Among the 46 pa- aging procedures were analyzed, showed an objective response rate of tients with single-vessel disease, 22 results showed that 123I-BMIPP and 34.6% (complete response, 3.7%; were classified as having mild CAD 99mTc-tetrafosmin SPECT imaging partial response, 30.8%; no change, (stenosis ϭ 50%–75%) and 24 as sensitivity was 61% in predicting 55.1%; progressive disease, 10.3%) having moderate-to-severe CAD (ste- functional improvement, with 94% in all patients and 33% in patients nosis Ն 76%). The sensitivity of myo- for 18F-FDG PET and 123I-BMIPP with non–small cell lung cancer. Bio- cardial perfusion alone was 50% for SPECT, and 76% for 18F-FDG PET distribution studies showed excellent the mild CAD subgroup and 83% for and 99mTc-tetrafosmin SPECT. The localization of radioactivity in tumors the moderate-to-severe subgroup. The specificity of 123I-BMIPP and 99mTc- in both systemically and intratumor- overall specificity was 90%. When tetrafosmin SPECT imaging in pre- ally injected patients. The authors wall motion analysis was added, sensi- dicting functional improvement was concluded that RIT with 131I-

36N THE JOURNAL OF NUCLEAR MEDICINE • Vol. 46 • No. 5 • May 2005 NEWSLINE chimeric tumor necrosis antibody dual-head camera systems with systemically administered intrave- was “well tolerated and can be used built-in anatomical imaging. Time– nous 123I-labeled rituximab to evalu- systemically or locally to treat refrac- activity data are included, along with ate uptake in primary central nervous tory tumors of the lung.” dosimetric calculations based on the system lymphoma (PCNSL). The Journal of Clinical Oncology model of the Medical Internal Radi- study included 4 patients with ation Dose committee. The “LundA- PCNSL who received a preinfusion Dose” program enables automatic of rituximab followed by 200–500 LundADose Method for quantification, image registration, MBq 123I-rituximab. SPECT imaging Absorbed Dose and absorbed dose calculations for was performed at 1, 24, and 48 hours Assessment in Therapy larger numbers of patient studies. after administration of the radiola- In an article published in the Feb- The method was evaluated in perfor- beled compound. One patient showed ruary issue of Cancer Biotherapy and mance of whole-body activity quan- very weak uptake of 123I-rituximab Radiopharmaceuticals (2005;20:92– tification for patients undergoing into tumor tissue, with uptake 9-fold 97), Sjogreen et al. from Lund Uni- radioimmunotherapy with 111In- or lower than blood-pool accumulation. versity (Sweden) described a new 90Y-labeled monoclonal. The authors concluded that these method for absorbed-dose assess- Cancer Biotherapy and data suggest that systemic monoclo- ment in radionuclide therapy. The Radiopharmaceuticals nal antibody–based radioimmuno- method is based on activity quantifi- therapy is not feasible in patients cation by a conjugate-view method- with PCNSL, because a sufficient ac- 123 ology that is applied to serial whole- I-Rituximab Imaging of tivity delivered to tumor would be body, anterior–posterior, scintillation CNS Lymphomas associated with severe hemotoxicity. camera scans. The method includes Dietlein et al. from the University They noted that whether “an uptake separate corrections for attenuation, of Cologne (Germany) reported in of therapeutic rituximab doses into scatter, and overlapping organs. Ad- the April issue of the European Jour- PCNSL can be achieved remains ditional development includes ac- nal of Haematology (2005;74:348– questionable.” commodation of the capabilities of 352) on dosimetric measurements of European Journal of Haematology

(Continued from page 32N) appointed as the mediator and will containing 99mTc destined for stress nonprescription drug and in January work closely with the 2 parties. The testing at a local hospital had been approved the Fleming pediatric prod- Government of Canada has agreed to stolen outside a Dunkin’ Donuts uct. have a representative as a formal ob- store in Seekonk, MA. The driver Department of Health and Human server in this process. Robert Van left the truck running while in the Services Adel, President and Chief Executive store. Police immediately entered Officer of AECL added, “We are en- the pickup truck’s information into MDS and AECL tering into this voluntary mediation a national computer alert system, Announce Mediation for process with the spirit and intent of and a regional broadcast was issued MAPLE Project arriving at a satisfactory resolution to to all area police departments about all of the outstanding issues, and we MDS Inc. and Atomic Energy of the potentially hazardous material. look forward to the successful commis- Canada Limited (AECL) announced The vehicle was found later in the sioning of the MAPLE reactors.” on March 11 that the 2 companies had day, with the radionuclide vials in- Atomic Energy of Canada Limited reached an agreement to seek a medi- tact and unopened. The thief was ated resolution of issues related to the unaware of the nature of the cargo, construction, commissioning, and op- Donut Stop Delays contained in a small “ammo” box in eration of the MAPLE facilities in Radionuclide Delivery the truck’s cab. Chalk River, Ontario. Ontario Appeals On March 10, The Pawtucket Court Judge Stephen Goudge has been (RI) Times reported that a truck The Pawtucket (RI) Times

Newsline 37N