Miolo rpm 124-3 (miolo 2).indd

Parkinson’s disease and
dopamine transporter
neuroimaging – a critical review
Laboratório Interdisciplinar de Neuroimagem e Cognição (LiNC), Universidade Federal de São Paulo and Instituto Israelita de Ensino e Pesquisa (IIEP), Hospital Israelita Albert Einstein (HIAE), São Paulo, Brazil disease patients manifest symptoms only when 50 to 80% of the nigrostriatal neurons are lost. Parkinson’s disease (PD) is a common neuro- neurodegenerative disorder characterized by Clinical diagnosis fails to identify individuals degenerative disorder that is mainly caused by dopaminergic neuron loss in the substantia the presence of Lewy bodies and progressive before they reach such a signifi cant loss of nigra. Several nuclear medicine radiotracers degeneration of dopaminergic neurons in the dopamine neurons. Such individuals would have been developed to evaluate PD diagnoses substantia nigra, with loss of their nerve termi- benefi t from early diagnosis, before dopamine and disease evolution in vivo in PD patients. nals in the basal ganglia structures, especially loss is too severe, with the aim of attempting to Positron emission tomography (PET) and single photon computerized emission tomog- in the striatum.1 Other etiopathogenic pro- implement the neuroprotective interventions raphy (SPECT) radiotracers for the dopamine cesses are suspected to incite and perpetuate that have been developed recently. Thus, im- transporter (DAT) provide good markers for PD, such as oxidative stress, mitochondrial provement in the accuracy of clinical diagnoses the integrity of the presynaptic dopaminergic system affected in PD. Over the last decade, of PD is needed for epidemiological studies radiotracers suitable for imaging the DAT have protein aggregation, which can lead to nigros- been the subject of most efforts. In this review, In this review, we discuss the relationship we provide a critical discussion on the utility of DAT imaging for Parkinson’s disease diagnosis The overall prevalence of PD is estimated between the dopamine system, especially the at 0.2% but rises with increasing age, affecting dopamine transporter (DAT), and Parkinson’s KEY WORDS: Parkinson disease. Dopamine.
as many as 0.5-1% of individuals aged 65-69 disease (PD). We also discuss the usefulness of Emission-computed tomography. Single-photon years and as many as 1-3% of individuals older DAT neuroimaging using positron emission emission-computerized tomography. Diagnosis.
than 80 years.3 PD diagnosis is substantially based on clinical symptoms and is character- sion computerized tomography (SPECT) for ized by resting tremor, rigidity, bradykinesia, and postural instability, and also favorable response to levodopa therapy,1,4 but few re- searchers have attempted to develop rigorous diagnostic criteria that can be applied consis- ing techniques such as magnetic resonance (CT) are not so useful for PD diagnosis. Parkinson’s disease in its initial phases of These techniques do, however, have a role clinical expression, three levels of diagnostic in the differential diagnosis with some other confi dence have been differentiated: defi nite, types of Parkinsonism. Researchers have been interested in developing sensitive diagnostic of possible and probable PD are based on techniques for early PD by assessing DAT clinical criteria alone, whereas the presence of concentrations in the striatum. The key to Lewy bodies in histopathological fi ndings is molecular imaging in nuclear medicine is required for defi nite PD diagnosis. However, radiotracers: substances that have high affi nity Lewy bodies are also present in many other and specifi city to a receptor site that is labeled diseases6,7 and are probably absent in autoso- with a radioisotope. These radioligands allow mal recessive juvenile Parkinsonism,8 which in vivo evaluation of receptor density and af- makes these diagnostic criteria not totally fi nity, measured as binding potential.12 The tracers are labeled with [123I] and [99mTc] for SPECT, or isotopes [11C], [18F], [15O] and 25% of cases with an antemortem clinical [13N] for PET. Although PET provides higher diagnosis of PD were found not to have PD resolution and better physical quantitative at postmortem examination.1,10 Parkinson’s capacity than SPECT, PET is less practical as a Sao Paulo Med J. 2006;124(3):168-75.
routine procedure because of its high cost and agents have been developed for diagnosing PD are chosen as ROI. Given that postmortem the shorter half-life of its radiotracers. On the and monitoring the treatment of PD patients, studies have shown a very low density of DAT other hand, SPECT uses isotopes with longer based on DAT antagonists such as methylphe- and SERT in occipital cortices and the cerebel- half-lives that can be stored on site.
nidate and cocaine (tropane derivatives).18,40,41 lum,82-84 these reference regions with absent (or low) DAT density are taken to indicate able for DAT imaging have been the subject rivatives gain potency through halogenation nondisplaceable DAT activity and are used of great investigative efforts. Several DAT of their phenyl rings. On the other hand, lack to assess nonspecifi c binding. Quantitative ligands have been successfully used as meth- of ester linkages between tropane and phenyl studies that are coregistered to the template or ods for evaluating neuronal loss, for PD moiety sites is the main mechanism for cocaine performed with anatomically adjusted ROIs diagnosis.11,13-19 For this reason, DAT ligands inactivation and degradation. Table 1 summa- (using templates or MRI overlay techniques) have become well-established markers that are rizes the DAT radiotracers that have reached or on a pixelwise basis, in which they self- useful for evaluating changes in presynaptic phase III or IV of clinical applications, includ- correspond exactly to the three-dimensional DAT sites in vivo and in vitro.
ing [11C] cocaine, [123I] β-CIT (2b-carboxy- ROI map, ensure that the results are highly methoxy-3b-[4-iodophenyl] tropane), [123I] observer-independent, precise, and reproduc- FE-CIT (iofl upane), [123I]/[18F]/[11C] FP-CIT ible, because of the automated processing.85 (N-[3-fl uoropropyl]-2ss-carbomethoxy-3ss- Striatal dopamine ROI areas for monoamine described 30 years ago. It is an 80-kDa pro- [4-iodophenyl]nortropane), [18F]/[11C] CFT transporters, mainly refl ecting SERT,82 are (2beta-carbomethoxy-3betafl uorophenyl-tro- visually positioned on the summed transversal ning regions with the carboxyl and amino pane), [123I]/[11C] altropane, [123I]/[11C] PE2I slices of the hypothalamus/midbrain (includ- termini residing intracellularly.20 The protein (N-{3-iodoprop-(2E)-enyl}-2beta-carboxyme- ing the raphe nuclei, substantia nigra and col- is externally glycosylated and is localized thoxy-3beta-{4’methylphenyl} nortropane), liculi), the thalamus and the medial prefrontal in the axonal membranes of nigrostriatal area at the striatal level. These areas have been identifi ed through magnetic resonance imag- gene is localized on chromosome 5p15.3.22-24 with [18F] dopa and PET labeling for dopa- ing scans using a reference atlas.86 If available, DAT is located on the plasma membrane of decarboxylase (the enzyme involved in dopa- ROI defi nition may be based on individual nerve terminals in a small number of neurons mine synthesis) was considered to be the gold morphology, as obtained by image fusion with in the brain, especially in the striatum and standard for evaluating nigral dopaminergic MRI, which is particularly important when nucleus accumbens, but also in the globus neurons in PD42,43 before the advent of DAT low specifi c binding is expected (e.g. in cases pallidus, cingulate cortex, olfactory tubercle, tracers. Tropane derivative studies ([11C] CFT of severe loss or blockade of the DAT).
and [123I] β-CIT) have shown a direct correla- the dopamine concentration in the synaptic tion between decreased DAT in the putamen ding to the product of the free receptor and PD symptoms.13,44 Descriptions of the density and affi nity, is calculated as the ratio presynaptic neurons; it plays a central role characteristics of several DAT tracers, includ- of striatal specifi c binding to steady-state in the spatial and temporal buffering of ing time to reach tracer equilibrium (scan free unmetabolized plasma tracer concentra- the released dopamine.26 Its activity can be time); tracer maximum accumulation (peak tion.87 Given that each tracer attains a state of regulated by presynaptic receptors, protein striatal activity); differential contrast imaging equilibrium in the striatal and occipital areas kinases, and membrane traffi cking.27-29 DAT in the striatal area and the rest of the brain, at a certain time after its injection, the ratio exerts vital infl uence on dopamine function, especially in the cerebellum (signal to noise point at this time is used as an estimate for by modulating locomotor activity, cognition ratio); and affi nity competition inhibition of the BP.88 The specifi c DAT BP in the basal and the reward system.30 Pharmacologically, serotonin and dopamine transporters (SERT: ganglia is calculated as the difference between DAT serves as the binding site for drugs of DAT) are given in Table 1.13,19,32,39,45-79 striatal activity and the reference region, i.e. abuse31 (e.g. cocaine and amphetamine) and the occipital activity (OA) at equilibrium. therapeutic agents32 (e.g. methylphenidate and The ratio of the total binding in the striatum bupropion). It has been observed that striatal minus the nondisplaceable binding in the DAT declines at a rate of approximately 6-7% tive evaluation techniques have to be used to OA divided by the OA refl ects the specifi c- per decade in the human striatum.33-35 The assess specifi c DAT binding in the striatum density of DAT can be used as a marker for and over its subregions (head of caudate and putamen). The investigator performing the tifi cation, it is necessary to be aware of pos- sible technical artifacts (pitfalls) such as head subject’s demographic characteristics.80 Trans- motion, attenuation artifacts and technical verse/oblique slices are usually chosen for ROI artifacts due to gamma camera problems.
sociation between PD and striatal DAT con- defi nition, such as transaxial slices oriented centration.37,38 Evaluation of DAT in human along the orbitomeatal line, and the two slices interaction with concomitant medications corresponding to the highest right and left must be taken into account and it is essential correlation of in vitro tracers such as [125I] striatal uptake are positioned on summed im- to objectively assess the semi-quantifi cation altropane and DAT reduction in PD.39 DAT ages.81 Data evaluation must always consider of striatal DAT binding. Inter-individual provides a good site for monitoring the integ- relevant morphological information (by CT quantitative results are based on compari- rity of the presynaptic dopaminergic systems or MRI), especially in structural lesions in the sons between specifi c DAT BP obtained in that are most affected in PD. Several DAT basal ganglia and the reference structures that the patients and normal controls that are Sao Paulo Med J. 2006;124(3):168-75.
preferably age-matched (thereby avoiding type of camera and the same image evaluation database, thus allowing comparative calcula- over-interpretation: age-dependency is a technique. If age-matched data comparisons tions for the different imaging protocols.
known pitfall/source of error). Age-specifi c are available, it is recommendable to use sensitivity and specifi city of DAT SPECT analytical approaches based on stereotactic imaging for differentiating patients with PD In routine clinical practice, even experi- from healthy subjects is greater than when normalities of DAT BP in an observer-inde- enced neurologists have diffi culty in differen- pendent manner. Moreover, it is important tiating early-stage PD from atypical Parkin- It is also important to utilize the same to establish a control group for the central sonian syndromes (APS).90,91 The accuracy of Table 1. Dopamine transporter radiotracers according to the literature
Peak striatal
Signal to
Scan time (min.)
activity (min.)
noise ratio
Logan et al., 199046Telang et al., 199947 CFT = 2beta-carbomethoxy-3betafl uorophenyl-tropane;WIN = [11C]2beta-carbomethoxy-3beta-(4-fl uorophenyl)-tropane; β-CIT = 2b-carboxymethoxy3b-[4-iodophenyl] tropane; RTI = [1R-(exo,exo)]- 3-[4-(iodo123)phenyl]-8-methyl-8-azabicyclo[3.2.1]o ctane-2-carb oxylic acid methyl ester; FE-CIT = iofl upane; FP-CIT = N-[3-fl uoropropyl]-2ss-carbomethoxy-3ss-[4-iodophenyl]nortropane; PE2I = N-{3-iodoprop-(2E)-enyl}-2beta-carboxymethoxy-3beta-{4’methylphenyl}nortropane; RTI-32 = methyl (1R-2-exo-3-exo)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate; TRODAT-1 = [2-[[2-[[[3-(4-chloro- phenyl)-8-methyl-8-azabicyclo[3, 2, 1]oct-2-yl]methyl] (2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3)]-oxo-[1R-(exo -exo)]; NA = not available; DAT = dopamine transporter; SERT = serotonin transporter; PET = photon emission tomography; SPECT = single photon emission computerized tomography. Sao Paulo Med J. 2006;124(3):168-75.
the clinical diagnoses of PD, multiple system ing assessed by [123I]IPT in patients with early atrophy (MSA), progressive supranuclear palsy Parkinson’s disease demonstrates the potential (PSP), cortical basal degeneration (CBD) and provides robust estimates of disease sever- of this method to detect preclinical disease.112 vascular Parkinsonism is imperfect and error ity, correlating with the duration of PD.101 Prunier et al. (2003), studying nonhuman rates can be as high as 25%.4 Although DAT However, variability in uptake values suggests primates chronically treated with 1-methyl-4- imaging is the best parameter for evaluating that factors other than nigrostriatal degenera- phenyl-1,2,3,6-tetrahydropyridine according dopamine neuron loss and differentiating be- tion may contribute towards disease severity. to a regimen that consistently produces a tween Parkinsonism and non-Parkinsonism, it There is a correlation with bradykinesia but progressive Parkinsonian state, have shown may not be useful for differentiating PD from not with tremor, thus suggesting that the that [123I]-PE2I SPECT was able to detect origin of tremors is beyond the DAT system. presymptomatic lesions of nigrostriatal neu- kinsonism.92,93 Postsynaptic dopamine recep- rons and suggested that this method could with or without the Parkinsonism gene has now be used clinically for early diagnosis of techniques such as diffusion weighted imaging now found that Parkinsonism-related disease or volumetry are more likely to contribute to may be associated with a higher degree of a differential diagnosis between PD/APS and nigrostriatal impairment, independent of the clinical severity of the disease, and more Although there is controversy in the literature, evaluating PD progression. DAT radiotrac- be helpful for differentiating between PSP and ers seem to be the best markers for identify- PD in routine clinical practice.96 Combining ing PD patients, with high sensitivity and this with D2 receptor imaging can differenti- good correlation between the H&Y and UP- specifi city. DAT reduction correlates with ate between MSA and PD,97 because each type DRS scales.103 This method is useful for early dopamine neurons loss in the substantia nigra of Parkinsonian syndrome has its own physio- PD detection,104 and it has been suggested that and striatum.26,114,115 This is why the striatal pathology and rates of dopamine neuron loss it may be useful for differential diagnosis of concentration of DAT, preferentially puta- and post-synaptic receptor compensation in some kinds of movement disorders.105 Results men DAT, is a highly sensitive parameter for the striatum (caudate and putamen). In con- from a crossover study have suggested that detecting early phases of PD.39 DAT ligands trast, the distinction between CBD and other are well-established markers that are useful in reliable alternative to [18F]-dopa PET in the evaluating changes in presynaptic DAT sites evaluation of clinical PD patients.106 A repro- ducibility study using TRODAT-1 scans from The PET isotopes and [123I] are produced 20 PD patients showed excellent test-retest in cyclotrons and have limited availability reliability in evaluating PD progression.107 and relatively high cost, thus limiting the The most-used radiotracer is [123I] β-CIT. In The diagnostic accuracy of [99mTc]-TRODAT-1 availability of such DAT tracers for routine an evaluation of 113 PD patients, there was SPECT showed sensitivity of 0.79 and specifi c- application in DAT imaging106 Studies have a good correlation between DAT density loss ity of 0.92 in distinguishing 29 patients with and PD symptoms (Unifi ed Parkinson’s Dis- early PD from 38 healthy volunteers.108 Fur- useful.105,116 The ready availability and ease of ease Rating Scale, UPDRS), and the decrease thermore, in a sample of patients with different use of [99mTc] agents using a modifi ed TRO- in signal ranged from 35% in a Hoehn-Yahr stages of PD and healthy controls, another DAT-1 preparation kit117 are advantages that (H&Y) stage I patient to 75% in an H&Y research group found good concordance when provide a powerful incentive for their routine stage V patient.92 Using [123I] β-CIT, a mul- visual interpretation of [99mTc]-TRODAT-1 ticenter study found sensitivity of 98% and SPET images was used to evaluate the pres- Although PD is characterized by selective specifi city of 83% for PD diagnosis, in dif- ence of PD (sensitivity 0.98 and specifi city loss of dopamine neurons in the basal ganglia ferentiation from PSP and essential tremor 0.86).109 Using age-matched PD patients and and substantia nigra, these are not the only (ET).39 A six-month follow-up study on 35 healthy controls, Weng et al. (2004) showed brain changes occurring in these patients’ suspected PD patients found that [123I] β-CIT brains. Several other changes leading to neuro- was more accurate (sensitivity 0.92; specifi city sensitivity and specifi city for measuring the psychological defi cits cannot be explained by 1.00) than the clinical diagnosis (sensitivity decrement of DAT in PD patients.110 A cross- dopamine loss.118 In a study on 32 PD patients 0.92; specifi city 0.30).98 A retrospective study sectional study on 96 early-stage patients com- using [123I] β-CIT, it was found that although on 72 early-stage untreated Parkinsonian paring [123I] FP-CIT and [99mTc] TRODAT-1, striatal uptake was correlated with clinical syndrome (PS) patients revealed lower caudate found sensitivity/specifi city of 0.95/0.86 and severity, the annual percentage loss of striatal nucleus binding ratios and higher putamen uptake did not correlate with the annual loss binding ratios among cases that were later in measurements of clinical function.119 On diagnosed or rediagnosed as APS and IPD, erature involving other tropane derivatives, the other hand, there was a non-signifi cant thus showing that striatal involvement ap- and so far only preliminary experiences have difference in progression rate across three peared to have little predictive value in these been presented. [18F] β-CFT was found to be scans obtained over a fi ve-year period among a sensitive marker for dopaminergic dysfunc- 24 early PD patients.120 In a longitudinal study tion that could be used in diagnoses, disease assessing PD progression, the annual rate of severity assessments and patient follow-up.47 reduction of striatal DAT uptake was approxi- 93% specifi city for differentiating between Reduced striatal dopamine transporter bind- mately 6 to 13% in PD patients, compared Sao Paulo Med J. 2006;124(3):168-75.
with 0 to 2.5% in healthy controls, which was exposure to enriched environments (a com- routine clinical studies and favors its general in line with the results from [18F] dopa-PET bination of exercise, social interaction and introduction. As noted, the application of studies.121-123 However, most of these studies learning);125 the use of MAO-inhibitors;126 these methods in our country is very recent. were conducted among patients with advanced L-dopa coadministered with the adenosine Today, the fi rst neuroimaging pilot study on PD.124 Furthermore, DAT tracers present cer- A2A receptor agonist;127 and gene neuropro- tain problems in evaluating PD progression, tective therapy models (neurotrophic factors, derway in Brazil for evaluating PD patients.132 because of changes in the DAT system (up or i.e. genes to prevent apoptosis or detoxify Several other research protocols using [99mTc] downregulation) induced by drug treatment, free radical species that protect and restore and this method has not been fully validated investigate DAT in neuropsychiatric disorders as an outcome measurement for trials on PD involving the dopaminergic system, such as treatments. Future studies should focus on early onset Parkinson’s disease, attention defi cit the early stages of PD, i.e. the time when and hyperactivity disorder (ADHD), obsessive- the diagnosis is uncertain and DAT imaging duced in cyclotrons and have limited avail- compulsive disorder (OCD), post-traumatic ability, relatively short half-life and high cost, stress disorder (PTSD) and schizophrenia.
thereby limiting the accessibility of DAT tracers.106 In Brazil, the use of those cyclotron- tion process, which indeed is the main phys- generated radioligands is limited by the vol- iopathology of PD as far as the early stages ume of tracer production, which is restricted ferential diagnosis between Parkinsonian and of the disease are concerned. In fact, few to certain government institutions.129 This non-Parkinsonian syndromes and in cases of studies have evaluated the usefulness of DAT restriction limits the availability of radiotracers uncertainty involving essential tremor. The imaging for providing clear diagnosis in the and, more importantly, inhibits the develop- high sensitivity and specifi city of SPECT semi- early stages of PD. Further studies examining ment of the radiopharmacy laboratories and quantitative images makes this method a useful the specifi city of the diagnosis of PD using radiochemists that are fundamental for the tool in the early clinical PD evaluation and in DAT imaging are needed. Nevertheless, early advance of molecular imaging in Brazil.130 preclinical screening for asymptomatic patients. dopamine neuron loss can easily be detected The advantage of tracers such as [99mTc] At the present moment, DAT imaging is the TRODAT-1 is the ready availability and ease best biomarker for evaluating dopamine neuron cation. Early dopamine neuron loss detection manipulation of 99mTc using a modifi ed prepa- loss, which is responsible for most of the motor enables interventions for minimizing and ration of TRODAT-1 by means of a kit.117 stabilizing these progressions by means of In Brazil, some animal studies using [99mTc] neuroprotection treatments. Although neu- easy to manipulate. Recent data suggest that roprotective therapy is still controversial and group performed the fi rst studies on humans it can be safely used in Brazil.131-133 Although so far non-existent for PD, several strategies using this tracer and obtained encouraging the current availability is restricted to research have been studied and it is hoped that they results. The data so far suggests that this centers, it is expected that it will soon be avail- will soon be in use. These strategies include tracer is an uncomplicated and reliable tool for 1. Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson 11. Brooks DJ. PET studies on the early and differential diagnosis of tomography in patients with parkinsonism. Eur J Nucl Med. disease. Arch Neurol. 1999;56(1):33-9.
Parkinson’s disease. Neurology. 1993;43(12 Suppl 6):S6-16.
2. Dawson TM, Dawson VL. Rare genetic mutations shed 12. Bressan RA, Erlandsson K, Jones HM, Mulligan RS, Ell PJ, 19. Innis RB, Seibyl JP, Scanley BE, et al. Single photon emission light on the pathogenesis of Parkinson disease. J Clin Invest. Pilowsky LS. Optimizing limbic selective D2/D3 receptor computed tomographic imaging demonstrates loss of striatal occupancy by risperidone: a [123I]-epidepride SPET study. J dopamine transporters in Parkinson disease. Proc Natl Acad 3. Tanner CM, Goldman SM. Epidemiology of Parkinson’s disease. Clin Psychopharmacol. 2003;23(1):5-14.
13. Frost JJ, Rosier AJ, Reich SG, et al. Positron emission tomo- 20. Iversen LL. Role of transmitter uptake mechanisms in synaptic 4. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of graphic imaging of the dopamine transporter with 11C-WIN neurotransmission. Br J Pharmacol. 1971;41(4):571-91.
clinical diagnosis of idiopathic Parkinson’s disease: a clinico- 35,428 reveals marked declines in mild Parkinson’s disease. Ann 21. Nirenberg MJ, Vaughan RA, Uhl GR, Kuhar MJ, Pickel VM. pathological study of 100 cases. J Neurol Neurosurg Psychiatry. The dopamine transporter is localized to dendritic and axonal 14. Guttman M, Burkholder J, Kish SJ, et al. [11C]RTI-32 plasma membranes of nigrostriatal dopaminergic neurons. J 5. Calne DB, Snow BJ, Lee C. Criteria for diagnosing Parkinson’s PET studies of the dopamine transporter in early dopa-naive disease. Ann Neurol. 1992;32(Suppl):S125-7.
Parkinson’s disease: implications for the symptomatic threshold. 22. Giros B, el Mestikawy S, Godinot N, et al. Cloning, pharmacologi- 6. Hansen L, Salmon D, Galasko D, et al. The Lewy body variant of cal characterization, and chromosome assignment of the human Alzheimer’s disease: a clinical and pathologic entity. Neurology. 15. Innis RB. Single-photon emission tomography imaging of dopamine transporter. Mol Pharmacol. 1992;42(3):383-90.
dopamine terminal innervation: a potential clinical tool in 23. Donovan DM, Vandenbergh DJ, Perry MP, et al. Human and 7. Gibb WR, Scaravilli F, Michund J. Lewy bodies and subacute Parkinson’s disease. Eur J Nucl Med. 1994;21(1):1-5.
mouse dopamine transporter genes: conservation of 5’-fl anking sclerosing panencephalitis. J Neurol Neurosurg Psychiatry. 16. Marek KL, Seibyl JP, Zoghbi SS, et al. [123I] beta-CIT/SPECT sequence elements and gene structures. Brain Res Mol Brain Res. imaging demonstrates bilateral loss of dopamine transporters in 8. Ishikawa A, Takahashi H. Clinical and neuropathological hemi-Parkinson’s disease. Neurology. 1996;46(1):231-7.
24. Vandenbergh DJ, Persico AM, Hawkins AL, et al. Human do- aspects of autosomal recessive juvenile parkinsonism. J Neurol. 17. Seibyl JP, Marek K, Sheff K, et al. Iodine-123-beta-CIT and pamine transporter gene (DAT1) maps to chromosome 5p15.3 iodine-123-FPCIT SPECT measurement of dopamine trans- and displays a VNTR. Genomics. 1992;14(4):1104-6.
9. Hughes AJ, Daniel SE, Blankson S, Lees AJ. A clinicopatho- porters in healthy subjects and Parkinson’s patients. J Nucl Med. 25. Ciliax BJ, Heilman C, Demchyshyn LL, et al. The dopamine logic study of 100 cases of Parkinson’s disease. Arch Neurol. transporter: immunochemical characterization and localization 18. Booij J, Tissingh G, Winogrodzka A, van Royen EA. Imag- in brain. J Neurosci. 1995;15(3 Pt 1):1714-23.
10. Agid Y. Parkinson’s disease: pathophysiology. Lancet. ing of the dopaminergic neurotransmission system using 26. Kish SJ, Shannak K, Hornykiewicz O. Uneven pattern of dopa- single-photon emission tomography and positron emission mine loss in the striatum of patients with idiopathic Parkinson’s Sao Paulo Med J. 2006;124(3):168-75.
disease. Pathophysiologic and clinical implications. N Engl J 49. Rinne JO, Bergman J, Ruottinen H, et al. Striatal uptake of a Parkinson’s disease by SPECT with altropane: a selective ligand novel PET ligand, [18F]beta-CFT, is reduced in early Parkinson’s for dopamine transporters. Synapse. 1998;29(2):128-41.
27. Batchelor M, Schenk JO. Protein kinase A activity may kineti- disease. Synapse. 1999;31(2):119-24.
68. Elmaleh DR, Fischman AJ, Shoup TM, et al. Preparation and cally upregulate the striatal transporter for dopamine. J Neurosci. 50. Madras BK, Spealman RD, Fahey MA, Neumeyer JL, Saha biological evaluation of iodine-125-IACFT: a selective SPECT JK, Milius RA. Cocaine receptors labeled by [3H]2 beta-car- agent for imaging dopamine transporter sites. J Nucl Med. 28. Chen N, Reith ME. Structure and function of the dopamine bomethoxy-3 beta-(4-fl uorophenyl)tropane. Mol Pharmacol. transporter. Eur J Pharmacol. 2000;405(1-3):329-39.
69. Emond P, Garreau L, Chalon S, et al. Synthesis and li- 29. Melikian HE, Buckley KM. Membrane traffi cking regulates 51. Morris ED, Babich JW, Alpert NM, et al. Quantifi cation gand binding of nortropane derivatives: N-substituted the activity of the human dopamine transporter. J Neurosci. of dopamine transporter density in monkeys by dynamic 2beta-carbomethoxy-3beta-(4’-iodophenyl)nortropane and PET imaging of multiple injections of 11C-CFT. Synapse. N-(3-iodoprop-(2E)-enyl)-2beta-carbomethoxy-3beta-(3’,4’- 30. Bressan RA, Crippa JA. The role of dopamine in reward and disubstituted phenyl)nortropane. New high-affi nity and selec- pleasure behaviour-review of data from preclinical research. Acta 52. Haaparanta M, Bergman J, Laakso A, Hietala J, Solin O. tive compounds for the dopamine transporter. J Med Chem. Psychiatr Scand Suppl. 2005;(427):14-21.
[18F]CFT ([18F]WIN 35,428), a radioligand to study the 31. Fowler JS, Volkow ND, Wolf AP, et al. Mapping cocaine dopamine transporter with PET: biodistribution in rats. Synapse. 70. Chalon S, Garreau L, Emond P, et al. Pharmacological charac- binding sites in human and baboon brain in vivo. Synapse. terization of (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy- 53. Brownell AL, Elmaleh DR, Meltzer PC, et al. Cocaine congeners 3beta-(4’-methylphenyl n ortropane as a selective and potent 32. Volkow ND, Ding YS, Fowler JS, et al. A new PET ligand for as PET imaging probes for dopamine terminals. J Nucl Med. inhibitor of the neuronal dopamine transporter. J Pharmacol the dopamine transporter: studies in the human brain. J Nucl 54. Gatley SJ, Ding YS, Volkow ND, Chen R, Sugano Y, Fowler 71. Hall H, Halldin C, Guilloteau D, et al. Visualization of the dopa- 33. Ma SY, Ciliax BJ, Stebbins G, et al. Dopamine transporter-im- JS. Binding of d-threo-[11C]methylphenidate to the dopamine mine transporter in the human brain postmortem with the new munoreactive neurons decrease with age in the human substantia transporter in vivo: insensitivity to synaptic dopamine. Eur J selective ligand [125I]PE2I. Neuroimage. 1999;9(1):108-16.
nigra. J Comp Neurol. 1999;409(1):25-37.
72. Guilloteau D, Emond P, Baulieu JL, et al. Exploration of 34. Scherman D, Desnos C, Darchen F, Pollak P, Javoy-Agid F, Agid 55. Laruelle M, Giddings SS, Zea-Ponce Y, et al. Methyl 3 beta-(4- the dopamine transporter: in vitro and in vivo characteriza- Y. Striatal dopamine defi ciency in Parkinson’s disease: role of [125I] iodophenyl)tropane-2 beta-carboxylate in vitro binding tion of a high-affi nity and high-specifi city iodinated tropane to dopamine and serotonin transporters under “physiological” derivative (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy- 35. van Dyck CH, Seibyl JP, Malison RT, et al. Age-related decline conditions. J Neurochem. 1994;62(3):978-86.
3beta-(4’-m ethylph enyl)nortropane (PE2I). Nucl Med Biol. in striatal dopamine transporter binding with iodine-123-beta- 56. Brucke T, Kornhuber J, Angelberger P, Asenbaum S, Frassine CITSPECT. J Nucl Med. 1995;36(7):1175-81.
H, Podreka I. SPECT imaging of dopamine and serotonin 73. Poyot T, Conde F, Gregoire MC, et al. Anatomic and 36. Uhl GR. Neurotransmitter transporters (plus): a promising new transporters with [123I]beta-CIT. Binding kinetics in the human biochemical correlates of the dopamine transporter ligand gene family. Trends Neurosci. 1992;15(7):265-8.
brain. J Neural Transm Gen Sect. 1993;94(2):137-46.
11C-PE2I in normal and parkinsonian primates: comparison 37. Wilson JM, Levey AI, Rajput A, et al. Differential changes in 57. Laruelle M, Wallace E, Seibyl JP, et al. Graphical, kinetic, and with 6-[18F]fluoro-L-dopa. J Cereb Blood Flow Metab. neurochemical markers of striatal dopamine nerve terminals in equilibrium analyses of in vivo [123I] beta-CIT binding to idiopathic Parkinson’s disease. Neurology. 1996;47(3):718-26.
dopamine transporters in healthy human subjects. J Cereb Blood 74. Kuikka JT, Tupala E, Bergstrom KA, Hiltunen J, Tiihonen 38. Niznik HB, Fogel EF, Fassos FF, Seeman P. The dopamine J. Iodine-123 labelled PE2I for dopamine transporter imag- transporter is absent in parkinsonian putamen and reduced in 58. Kuikka JT, Akerman K, Bergstrom KA, et al. Iodine-123 ing: infl uence of age in healthy subjects. Eur J Nucl Med. the caudate nucleus. J Neurochem. 1991;56(1):192-8.
labelled N-(2-fl uoroethyl)-2 beta-carbomethoxy-3 beta-(4- 39. Madras BK, Gracz LM, Fahey MA, et al. Altropane, a SPECT iodophenyl)nortropane for dopamine transporter imaging in 75. Repo E, Kuikka JT, Bergstrom KA, Karhu J, Hiltunen J, or PET imaging probe for dopamine neurons: III. Human the living human brain. Eur J Nucl Med. 1995;22(7):682-6.
Tiihonen J. Dopamine transporter and D2-receptor den- dopamine transporter in postmortem normal and Parkinson’s 59. Antonini A, Moresco RM, Gobbo C, et al. The status of sity in late-onset alcoholism. Psychopharmacology (Berl). diseased brain. Synapse. 1998;29(2):116-27.
dopamine nerve terminals in Parkinson’s disease and essential 40. Seibyl JP, Marek KL, Quinlan D, et al. Decreased single-photon tremor: a PET study with the tracer [11-C]FE-CIT. Neurol Sci. 76. Choi SR, Kung MP, Plossl K, Meegalla S, Kung HF. An im- emission computed tomographic [123I] beta-CIT striatal uptake proved kit formulation of a dopamine transporter imaging agent: correlates with symptom severity in Parkinson’s disease. Ann 60. Tissingh G, Booij J, Bergmans P, et al. Iodine-123-N-omega-fl u- [Tc-99m]TRODAT-1. Nucl Med Biol. 1999;26(4):461-6.
oropropyl-2beta-carbomethoxy-3beta-(4-iod ophenyl)tropane 77. Acton PD, Kushner SA, Kung MP, Mozley PD, Plossl K, Kung 41. A multicenter assessment of dopamine transporter imaging with SPECT in healthy controls and early-stage, drug-naive HF. Simplifi ed reference region model for the kinetic analysis DOPASCAN/SPECT in parkinsonism. Parkinson Study Group. Parkinson’s disease. J Nucl Med. 1998;39(7):1143-8.
of [99mTc]TRODAT-1 binding to dopamine transporters in 61. Booij J, Speelman JD, Horstink MW, Wolters EC. The nonhuman primates using single-photon emission tomography. 42. Leenders KL, Palmer AJ, Quinn N, et al. Brain dopamine clinical benefi t of imaging striatal dopamine transporters with metabolism in patients with Parkinson’s disease measured with [123I]FP-CIT SPET in differentiating patients with presynaptic 78. Kao PF, Tzen KY, Yen TC, et al. The optimal imaging time for positron emission tomography. J Neurol Neurosurg Psychiatry. parkinsonism from those with other forms of parkinsonism. Eur [99Tcm]TRODAT-1/SPET in normal subjects and patients with Parkinson’s disease. Nucl Med Commun. 2001;22(2):151-4.
43. Brooks DJ, Ibanez V, Sawle GV, et al. Differing patterns of 62. Lundkvist C, Halldin C, Ginovart N, Swahn CG, Farde L. [18F] 79. Lee CS, Samii A, Sossi V, et al. In vivo positron emission to- striatal 18F-dopa uptake in Parkinson’s disease, multiple sys- beta-CIT-FP is superior to [11C] beta-CIT-FP for quantitation of mographic evidence for compensatory changes in presynaptic tem atrophy, and progressive supranuclear palsy. Ann Neurol. the dopamine transporter. Nucl Med Biol. 1997;24(7):621-7.
dopaminergic nerve terminals in Parkinson’s disease. Ann 63. Chaly T, Dhawan V, Kazumata K, et al. Radiosynthesis 44. Seibyl JP. Single-photon emission computed tomography of of [18F] N-3-fluoropropyl-2-beta-carbomethoxy-3-beta- 80. Tatsch K, Asenbaum S, Bartenstein P, et al. European Association the dopamine transporter in parkinsonism. J Neuroimaging. (4-iodophenyl) nortropane and the first human study of Nuclear Medicine procedure guidelines for brain neurotrans- with positron emission tomography. Nucl Med Biol. mission SPET using (123)I-labelled dopamine D(2) transporter 45. Ritz MC, Cone EJ, Kuhar MJ. Cocaine inhibition of ligand ligands. Eur J Nucl Med Mol Imaging. 2002;29(10):BP30-5.
binding at dopamine, norepinephrine and serotonin transport- 64. Abi-Dargham A, Gandelman MS, DeErausquin GA, et al. 81. Laine TP, Ahonen A, Torniainen P, et al. Dopamine transporters ers: a structure-activity study. Life Sci. 1990;46(9):635-45.
SPECT imaging of dopamine transporters in human brain increase in human brain after alcohol withdrawal. Mol Psychia- 46. Logan J, Fowler JS, Volkow ND, et al. Graphical analysis of with iodine-123-fl uoroalkyl analogs of beta-CIT. J Nucl Med. reversible radioligand binding from time-activity measurements 82. Laruelle M, Vanisberg MA, Maloteaux JM. Regional and applied to [N-11C-methyl]-(-)-cocaine PET studies in human 65. Madras BK, Meltzer PC, Liang AY, Elmaleh DR, Babich J, subcellular localization in human brain of [3H]paroxetine subjects. J Cereb Blood Flow Metab. 1990;10(5):740-7.
Fischman AJ. Altropane, a SPECT or PET imaging probe for binding, a marker of serotonin uptake sites. Biol Psychiatry. 47. Telang FW, Volkow ND, Levy A, et al. Distribution of tracer dopamine neurons: I. Dopamine transporter binding in primate levels of cocaine in the human brain as assessed with averaged 83. Palacios JM, Camps M, Cortes R, Probst A. Mapping dopa- [11C] cocaine images. Synapse. 1999;31(4):290-6.
66. Madras BK, Gracz LM, Meltzer PC, et al. Altropane, a SPECT mine receptors in the human brain. J Neural Transm Suppl. 48. Rinne JO, Ruottinen H, Bergman J, Haaparanta M, Sonninen or PET imaging probe for dopamine neurons: II. Distribu- P, Solin O. Usefulness of a dopamine transporter PET ligand tion to dopamine-rich regions of primate brain. Synapse. 84. De Keyser J, Ebinger G, Vauquelin G. Evidence for a widespread [(18)F]beta-CFT in assessing disability in Parkinson’s disease. dopaminergic innervation of the human cerebral neocortex. J Neurol Neurosurg Psychiatry. 1999;67(6):737-41.
67. Fischman AJ, Bonab AA, Babich JW, et al. Rapid detection of Sao Paulo Med J. 2006;124(3):168-75.
85. Schwarz J, Storch A, Koch W, Pogarell O, Radau PE, Tatsch 103. Weng YH, Yen TC, Chen MC, et al. Sensitivity and specifi city of 122. Chouker M, Tatsch K, Linke R, Pogarell O, Hahn K, Schwarz K. Loss of dopamine transporter binding in Parkinson’s disease 99mTc-TRODAT-1 SPECT imaging in differentiating patients J. Striatal dopamine transporter binding in early to moderately follows a single exponential rather than linear decline. J Nucl with idiopathic Parkinson’s disease from healthy subjects. J Nucl advanced Parkinson’s disease: monitoring of disease progression over 2 years. Nucl Med Commun. 2001;22(6):721-5.
86. Talairach J, Tournoux P. Co-planar stereotaxic atlas of the human 104. Huang WS, Lin SZ, Lin JC, Wey SP, Ting G, Liu RS. Evalua- 123. Staffen W, Mair A, Unterrainer J, Trinka E, Ladurner G. Measur- tion of early-stage Parkinson’s disease with 99mTc-TRODAT-1 ing the progression of idiopathic Parkinson’s disease with [123I] 87. Schneier FR, Liebowitz MR, Abi-Dargham A, Zea-Ponce Y, Lin imaging. J Nucl Med. 2001;42(9):1303-8.
beta-CIT SPECT. J Neural Transm. 2000;107(5):543-52.
SH, Laruelle M. Low dopamine D(2) receptor binding potential 105. Kanyo B, Argyelan M, Dibo G, et al. Dopamintranszporter- 124. Ravina B, Eidelberg D, Ahlskog JE, et al. The role of radiotracer in social phobia. Am J Psychiatry. 2000;157(3):457-9.
vizsgálatok egyfoton-emissziós komputertomográfi ával (SPECT) imaging in Parkinson disease. Neurology. 2005;64(2):208-15.
88. Abi-Dargham A, Gandelman MS, DeErausquin GA, et al. mozgászavarokkal járó kórképekben. [Imaging of dopamine 125. Faherty CJ, Raviie Shepherd K, Herasimtschuk A, Smeyne RJ. SPECT imaging of dopamine transporters in human brain transporter with Tc99m-Trodat-SPECT in movement disor- Environmental enrichment in adulthood eliminates neuronal with iodine-123-fl uoroalkyl analogs of beta-CIT. J Nucl Med. ders]. Ideggyogy Sz. 2003;56(7-8):231-40.
death in experimental Parkinsonism. Brain Res Mol Brain Res. 106. Huang WS, Chiang YH, Lin JC, Chou YH, Cheng CY, Liu 89. Weng YH, Yen TC, Chen MC, et al. Sensitivity and specifi city of RS. Crossover study of (99m)Tc-TRODAT-1 SPECT and 126. Riederer P, Lachenmayer L, Laux G. Clinical applications of 99mTc-TRODAT-1 SPECT imaging in differentiating patients (18)F-FDOPA PET in Parkinson’s disease patients. J Nucl Med. MAO-inhibitors. Curr Med Chem. 2004;11(15):2033-43.
with idiopathic Parkinson’s disease from healthy subjects. J Nucl 127. Agnati LF, Leo G, Vergoni AV, et al. Neuroprotective effect of 107. Hwang WJ, Yao WJ, Wey SP, Ting G. Reproducibility of 99mTc- L-DOPA co-administered with the adenosine A2A receptor 90. Lingford-Hughes A. There is more to dopamine than just plea- TRODAT-1 SPECT measurement of dopamine transporters in agonist CGS 21680 in an animal model of Parkinson’s disease. sure. Commentary on Volkow et al. ‘Role of dopamine in drug Parkinson’s disease. J Nucl Med. 2004;45(2):207-13.
reinforcement and addiction in humans: results from imaging 108.Chou KL, Hurtig HI, Stern MB, et al. Diagnostic accuracy 128. Fraix V. Thérapie génique et maladie de Parkinson. [Gene therapy studies’. Behav Pharmacol. 2002;13(5-6):367-70.
of [99mTc]TRODAT-1 SPECT imaging in early Parkinson’s for Parkinson’s disease]. Rev Med Interne. 2004;25(7):524-7.
91. Poewe W, Wenning G. The differential diagnosis of Parkinson’s disease. Parkinsonism Relat Disord. 2004;10(6):375-9.
129. Bressan RA, Bigliani V, Pilowsky LS. Neuroimagem de recep- disease. Eur J Neurol. 2002;9(Suppl 3):23-30.
109. Huang WS, Lee MS, Lin JC, et al. Usefulness of brain 99mTc- tores D2 de dopamina na esquizofrenia. [Neuroimaging of 92. Brucke T, Asenbaum S, Pirker W, et al. Measurement of the TRODAT-1 SPET for the evaluation of Parkinson’s disease. Eur D2 dopamine receptors in schizophrenia]. Rev Bras Psiquiatr. dopaminergic degeneration in Parkinson’s disease with [123I] J Nucl Med Mol Imaging. 2004;31(2):155-61.
2001;23(Supl 1):SI46:SI64-SI49-SI64.
beta-CIT and SPECT. Correlation with clinical fi ndings and 110.Weng YH, Yen TC, Chen MC, et al. Sensitivity and specifi city of 130. Costa DC, Oliveira JM, Bressan RA. PET e SPECT em neu- comparison with multiple system atrophy and progressive 99mTc-TRODAT-1 SPECT imaging in differentiating patients rologia e psiquiatria: do básico às aplicacöes clínicas. [PET and supranuclear palsy. J Neural Transm Suppl. 1997;50:9-24.
with idiopathic Parkinson’s disease from healthy subjects. J Nucl SPECT in Neurology and Psychiatry: From the basic to the 93. Plotkin M, Amthauer H, Klaffke S, et al. Combined 123I- clinical applications]. Rev Bras Psiquiatr. 2001;23(Supl 1):SI4: FP-CIT and 123I-IBZM SPECT for the diagnosis of par- 111.Van Laere K, De Ceuninck L, Dom R, et al. Dopamine trans- kinsonian syndromes: study on 72 patients. J Neural Transm. porter SPECT using fast kinetic ligands: 123I-FP-beta-CIT 131. Shih MC, Rodrigues GS, Cuyumjian PR, et al. SPECT com versus 99mTc-TRODAT-1. Eur J Nucl Med Mol Imaging. [99mTc]-TRODAT-1; defi nição de protocolo de aquisição 94. Seppi K, Schocke MF, Esterhammer R, et al. Diffusion-weighted com marcador de transportador dopaminérgico. Rev Imagem. imaging discriminates progressive supranuclear palsy from PD, 112.Schwarz J, Linke R, Kerner M, et al. Striatal dopamine trans- 2004;26(Suplemento 1):100 [abstract].
but not from the parkinson variant of multiple system atrophy. porter binding assessed by [I-123]IPT and single photon emis- 132. Shih MC, Amaro E, Goulart FO, et al. Striatal functional sion computed tomography in patients with early Parkinson’s imaging [99mTc]-TRODAT-1 SPECT and spectroscopic from 95. Schreckenberger M, Hagele S, Siessmeier T, et al. The dopamine disease: implications for a preclinical diagnosis. Arch Neurol. magnetic resonance study to evaluate dopamine neuron density. D2 receptor ligand 18F-desmethoxyfallypride: an appropriate J Nucl Med. 2005;46(Suppl 5):215. [poster].
fl uorinated PET tracer for the differential diagnosis of parkin- 113. Prunier C, Bezard E, Montharu J, et al. Presymptomatic diag- 133. Shih MC, Amaro Jr E, Ferraz HB, et al. Neuroimaging of the sonism. Eur J Nucl Med Mol Imaging. 2004;31(8):1128-35.
nosis of experimental Parkinsonism with 123I-PE2I SPECT. Dopamine Transporter in Parkinson´s Disease – First study using 96. Antonini A, Benti R, De Notaris R, et al. 123I-Iofl upane/SPECT [99mTc]-TRODAT-1 and SPECT in Brazil. Arq Neuropsiquiatr binding to striatal dopamine transporter (DAT) uptake in patients 114. Kaufman MJ, Madras BK. Severe depletion of cocaine rec- with Parkinson’s disease, multiple system atrophy, and progressive ognition sites associated with the dopamine transporter in supranuclear palsy. Neurol Sci. 2003;24(3):149-50.
Parkinson’s-diseased striatum. Synapse. 1991;9(1):43-9.
97. Knudsen GM, Karlsborg M, Thomsen G, et al. Imaging of 115. Wilson JM, Levey AI, Rajput A, et al. Differential changes in dopamine transporters and D2 receptors in patients with neurochemical markers of striatal dopamine nerve terminals in Parkinson’s disease and multiple system atrophy. Eur J Nucl idiopathic Parkinson’s disease. Neurology. 1996;47(3):718-26.
Med Mol Imaging. 2004;31(12):1631-8.
116. Mozley PD, Schneider JS, Acton PD, et al. Binding of 98. Jennings DL, Seibyl JP, Oakes D, Eberly S, Murphy J, Marek K. [99mTc]TRODAT-1 to dopamine transporters in patients (123I) beta-CIT and single-photon emission computed tomo- with Parkinson’s disease and in healthy volunteers. J Nucl Med. graphic imaging vs clinical evaluation in Parkinsonian syndrome: unmasking an early diagnosis. Arch Neurol. 2004;61(8):1224-9.
117. Choi SR, Kung MP, Plossl K, Meegalla S, Kung HF. An im- 99. Stoffers D, Booij J, Bosscher L, Winogrodzka A, Wolters EC, proved kit formulation of a dopamine transporter imaging agent: Berendse HW. Early-stage [123I]beta-CIT SPECT and long-term [Tc-99m]TRODAT-1. Nucl Med Biol. 1999;26(4):461-6.
clinical follow-up in patients with an initial diagnosis of Parkinson’s 118. Gibb WR. Functional neuropathology in Parkinson’s disease. disease. Eur J Nucl Med Mol Imaging. 2005;32(6):689-95.
100. Benamer TS, Patterson J, Grosset DG, et al. Accurate differentia- 119. Marek K, Innis R, van Dyck C, et al. [123I]beta-CIT SPECT tion of parkinsonism and essential tremor using visual assessment imaging assessment of the rate of Parkinson’s disease progression. of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov Disord. 2000;15(3):503-10.
120. Pirker W, Holler I, Gerschlager W, Asenbaum S, Zettinig G, Acknowledgements: R.A. Bressan is supported by a
PRO-DOC research grant from Coordenação de Aper- 101. Benamer HT, Patterson J, Wyper DJ, Hadley DM, Macphee Brucke T. Measuring the rate of progression of Parkinson’s dis- feiçoamento de Pessoal de Nível Superior (CAPES). M.C. GJ, Grosset DG. Correlation of Parkinson’s disease severity ease over a 5-year period with beta-CIT SPECT. Mov Disord. Shih is supported by a PhD scholarship from CAPES and and duration with 123I-FP-CIT SPECT striatal uptake. Mov Instituto Israelita de Ensino e Pesquisa Albert Einstein.
121. Pirker W, Djamshidian S, Asenbaum S, et al. Progression of Sources of funding: Not declared
102. Varrone A, Pellecchia MT, Amboni M, et al. Imaging of dopa- dopaminergic degeneration in Parkinson’s disease and atypical Confl ict of interest: Not declared
Date of fi rst submission: July 28, 2005
minergic dysfunction with [123I]FP-CIT SPECT in early-onset parkinsonism: a longitudinal beta-CIT SPECT study. Mov Last received: May 29, 2006
parkin disease. Neurology. 2004;63(11):2097-103.
Accepted: May 30, 2006
Sao Paulo Med J. 2006;124(3):168-75.
Ming Chi Shih, MD. Laboratório Interdisciplinar de
Doença de Parkinson e neuroimagem do transportador de dopamina – uma revisão crítica
Neuroimagem e Cognição (LiNC), Universidade Federal de São Paulo; and Instituto Israelita de Ensino e Pesquisa A doença de Parkinson (DP) é uma desordem neurodegenerativa causada por perda de neurônios do- (IIEP), Hospital Israelita Albert Einstein (HIAE), São Paulo, paminérgicos na substância negra. Vários traçadores da medicina nuclear têm sido desenvolvidos para avaliar o diagnóstico e acompanhamento da DP. Traçadores para o transportador de dopamina (TDA) utilizados na tomografi a por emissão de pósitrons (PET) e tomografi a por emissão de fóton único (SPECT) Marcelo Queiroz Hoexter, MD. Laboratório Interdisci-
plinar de Neuroimagem e Cognição (LiNC), Universidade demonstram boa marcação na integridade de sistema dopaminergico pré-sináptico, afetada na DP. Na Federal de São Paulo, São Paulo, Brazil.
última década, radiotraçadores apropriados para imagens de TDA têm sido mais estudados. Nesta revisão, provemos uma discussão crítica sobre a utilidade dessas imagens de TDA para o diagnóstico de Luiz Augusto Franco de Andrade MD, PhD. Instituto
DP (sensibilidade e especifi cidade).
Israelita de Ensino e Pesquisa (IIEP), Hospital Israelita Albert Einstein (HIAE), São Paulo, Brazil. PALAVRAS-CHAVE: Doença de Parkinson. Dopamina. Tomografi a computadorizada de emissão. Tomografi a
Rodrigo Affonseca Bressan, MD, PhD. Laboratório
computadorizada de emissão de fóton único. Diagnóstico.
Interdisciplinar de Neuroimagem e Cognição (LiNC), Uni-versidade Federal de São Paulo, São Paulo, Brazil.
Address for correspondence:
Ming Chi Shih
Rodrigo Affonseca Bressan
LiNC - Laboratório Interdisciplinar de Neuroimagem e Cognição, Departamento de PsiquiatriaUniversidade Federal de São PauloRua Dr. Bacelar, 334São Paulo (SP) — Brasil – CEP 04026-001Tel. (+55 11) 5084-7060Fax. (+55 11) 5084-7061E-mail: [email protected]: [email protected] Copyright 2006, Associação Paulista de Medicina Sao Paulo Med J. 2006;124(3):168-75.

Source: http://fundelta.com.br/webroot/doc/7f87eabd52.pdf


Studies of Nipent(R) in Combination Cancer Therapies for Treatment of Chronic Lymphocytic Leukemia and Graft-versus Host Disease (GVHD) Presented at American Society of Hematology Annual Meeting DUBLIN, Calif., Dec. 9 /PRNewswire-FirstCall/ -- SuperGen, Inc. (Nasdaq: SUPG) announced that abstracts from five studies of its anticancer drug Nipent® (pentostatin for injection) will be presented


Sleep_19-20-V3N5 10/17/08 6:19 PM Page 19Sleep Diagnosis and Therapy 2008; V3 N5, P19-20 K. Hansen Care of Patients at Risk for Sleep Apnea Who Receive Sedation Sleep apnea is the most widely known sleep disorder besidespatient for the effects of sedation, it is critical to differentiateinsomnia. Estimates are that more than 18 million people havebetween sedation and sleepiness: does the pa

© 2010-2017 Pdf Pills Composition