florbenazine-f-18 and Parkinson-Disease

Vesicular monoamine transporter 2 (VMAT2) is highly expressed in the endocrine cells and brain. We investigated the biodistribution and radiation dosimetry of (2R,3R,11bR)-9-(3-(18)F-fluoropropoxy)-3-isobutyl-10-methoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido[2,1-a]isoquinolin-2-ol ((18)F-FP-(+)-dihydrotetrabenazine [DTBZ] or (18)F-AV-133), a potential VMAT2 imaging agent showing encouraging results in humans, to facilitate its future clinical use.. Nine healthy human subjects (mean age +/- SD, 58.6 +/- 4.2 y) were enrolled for the whole-body PET scan. Serial images were acquired for 3 h immediately after a bolus injection of 390.7 +/- 22.9 MBq of (18)F-AV-133 per individual. The source organs were delineated on PET/CT images. The OLINDA/EXM application was used to determine the equivalent dose for individual organs.. The radiotracer did not show any noticeable adverse effects for the 9 subjects examined. The radioactivity uptake in the brain was the highest at 7.5% +/- 0.6% injected dose at 10 min after injection. High absorbed doses were found in the pancreas, liver, and upper large intestine wall. The highest-dosed organ, which received 153.3 +/- 23.8 microGy/MBq, was the pancreas. The effective dose equivalent and effective dose for (18)F-AV-133 were 36.5 +/- 2.8 and 27.8 +/- 2.5 microSv/MBq, respectively. These values are comparable to those reported for any other (18)F-labeled radiopharmaceutical.. (18)F-AV-133 is safe, with appropriate biodistribution and radiation dosimetry for imaging VMAT2 sites in humans.

Topics: Drug-Related Side Effects and Adverse Reactions; Female; Fluorine Radioisotopes; Humans; Male; Middle Aged; Molecular Imaging; Parkinson Disease; Positron-Emission Tomography; Radiometry; Tetrabenazine; Vesicular Monoamine Transport Proteins

There are limited validated biomarkers in Parkinson disease (PD) which substantially hinders the ability to monitor disease progression and consequently measure the efficacy of disease-modifying treatments. Imaging biomarkers, such as vesicular monoamine transporter type 2 (VMAT2) PET, enable enhanced diagnostic accuracy and detect early neurodegenerative changes associated with prodromal PD. This study sought to assess whether. Over the 26-month interval, a significant decline in PET signal was observed in all 3 regions in participants with PD (N = 26) compared with NC (N = 12), consistent with a decrease in VMAT2 level and ongoing neurodegeneration. Imaging trajectory calculations suggest that the neurodegeneration in PD occurs over ∼33 years [CI: 27.2-39.5], with ∼10.5 years [CI: 9.1-11.3] of degeneration in the posterior putamen before it becomes detectable on a VMAT2 PET scan, a further ∼6.5 years [CI: 1.6-12.7] until symptom onset, and a further ∼3 years [CI: 0.3-8.7] until clinical diagnosis.. Over a 2-year period,. This study provides Class IV evidence that VMAT2 PET can detect patients with Parkinson disease and quantify progression over a 2-year window.

Topics: Biomarkers; Disease Progression; Humans; Parkinson Disease; Positron-Emission Tomography; Vesicular Monoamine Transport Proteins

Lactacystin has been used to establish rodent models of Parkinson disease (PD), with cerebral α-synuclein inclusions. This study evaluated the uptake of [. Adult male Sprague-Dawley rats were randomly treated with a single intracranial dose of lactacystin (2 or 5 μg) or saline (served as the sham control) into the left medial forebrain bundle. A 30-min static [. Both the 2- and 5-μg lactacystin-treated groups exhibited significantly decreased specific [. In this PD model, lactacystin-induced dopaminergic terminal damage in the ipsilateral striatum could be clearly visualized through in vivo [

Topics: Acetylcysteine; Animals; Brain; Disease Models, Animal; Fluorine Radioisotopes; Image Processing, Computer-Assisted; Male; Parkinson Disease; Rats; Rats, Sprague-Dawley; Tetrabenazine

18F-9-Fluoropropyl-(+)-dihydrotetrabenazine [18F-FP-(+)-DTBZ] positron emission tomography (PET) has been shown to detect dopaminergic neuron loss associated with Parkinson's disease (PD) in human and neurotoxin-induced animal models. A polyphenol compound, magnolol, was recently proposed as having a potentially restorative effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-treated animal models. In this study, 18F-FP-(+)-DTBZ PET was used to determine the therapeutic efficacy of magnolol in an MPTP-PD mouse model that was prepared by giving an intraperitoneally (i.p.) daily dose of 25 mg/kg MPTP to male C57BL/6 mice for 5 consecutive days. Twenty-minute static 18F-FP-(+)-DTBZ PET scans were performed before MPTP treatment and 5 days after the termination of MPTP treatment to set up the baseline control. Half of the MPTP-treated mice then received a daily dose of magnolol (10 mg/kg dissolved in corn oil, i.p.) for 6 days. 18F-FP-(+)-DTBZ PET imaging was performed the day after the final treatment. All 18F-FP-(+)-DTBZ PET images were analysed and the specific uptake ratio (SUr) was calculated. Ex vivo autoradiography (ARG) and corresponding immunohistochemistry (IHC) studies were conducted to confirm the distribution of dopaminergic terminals in the striatum. The striatal SUr ratios of 18F-FP-(+)-DTBZ PET images for the Sham, the MPTP, and the MPTP + Magnolol-treated groups were 1.25 ± 0.05, 0.75 ± 0.06, and 1.00 ± 0.11, respectively (n = 4 for each group). The ex vivo 18F-FP-(+)-DTBZ ARG and IHC results correlated favourably with the PET imaging results. 18F-FP-(+)-DTBZ PET imaging suggested that magnolol post-treatment may reverse the neuronal damage in the MPTP-lesioned PD mice. In vivo imaging of the striatal vesicular monoamine transporter type 2 (VMAT2) distribution using 18F-FP-(+)-DTBZ animal PET is a useful method to evaluate the efficacy of therapeutic drugs i.e., magnolol, for the management of PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Biphenyl Compounds; Corpus Striatum; Disease Models, Animal; Fluorine Radioisotopes; Humans; Lignans; Mice; Neurons; Parkinson Disease; Parkinson Disease, Secondary; Positron-Emission Tomography; Tetrabenazine; Vesicular Monoamine Transport Proteins

Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1-42 (Aβ1-42), phosphorylated tau (181P) (p-tau), and total tau (t-tau), have long been associated with the development of Parkinson disease (PD) and other neurodegenerative diseases. In this investigation, we reported the assessment of CSF biomarkers and their correlations with vesicular monoamine transporter 2 (VMAT2) bindings measured with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-AV133) that is being developed as a biomarker for PD. We test the hypothesis that monoaminergic degeneration was correlated with CSF biomarker levels in untreated PD patients.. The available online data from the Parkinson's Progression Markers Initiative study (PPMI) project were collected and analyzed, which include demographic information, clinical evaluations, CSF biomarkers (α-syn, Aβ1-42, p-tau, and t-tau), 18F-AV133 brain PET, and T1 weighted MRIs. Region of interest (ROI) and voxel-wise Pearson correlation between standardized uptake value ratio (SUVR) and CSF biomarkers were calculated.. Our major findings are: 1) Compared with controls, CSF α-syn and tau levels decreased significantly in PD; 2) α-syn was closely correlated with Aβ1-42 and tau in PD, especially in early-onset patients; and 3) hypothesis-driven ROI analysis found a significant negative correlation between CSF Aβ1-42 levels and VMAT2 densities in post cingulate, left caudate, left anterior putamen, and left ventral striatum in PDs. CSF t-tau and p-tau levels were significantly negatively related to VMAT2 SUVRs in substantia nigra and left ventral striatum, respectively. Voxel-wise analysis showed that left caudate, parahippocampal gyrus, insula and temporal lobe were negatively correlated with Aβ1-42. In addition, superior frontal gyrus and transverse temporal gyrus were negatively correlated with CSF p-tau levels.. These results suggest that monoaminergic degeneration in PD is correlated with CSF biomarkers associated with cognitive impairment in neurodegenerative diseases including Alzheimer's disease. The association between loss of dopamine synaptic function and pathologic protein accumulations in PD indicates an important role of CSF biomarkers in PD development.

Topics: Aged; alpha-Synuclein; Amyloid beta-Peptides; Biomarkers; Brain; Female; Fluorine Radioisotopes; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Parkinson Disease; Pilot Projects; Positron-Emission Tomography; tau Proteins; Tetrabenazine; Vesicular Monoamine Transport Proteins

Recent experimental studies revealed that dopamine neuron dysfunction in chronic manganism may be due to a reduced capacity of dopamine release in the striatum. The findings imposed further difficulty in the differential diagnosis between manganism and IPD. We conducted a long-term clinical follow-up study of 4 manganism patients, applying a new tracer (18)F-9-fluoropropyl-(+)-dihydrotetrabenazine ((18)F-AV-133) with positron emission tomography (PET). Twenty age-matched subjects including 4 manganism patients, 8 idiopathic Parkinson's disease (IPD) patients, and 8 healthy controls were enrolled for comparison. Volumes of interest of the bilateral putamen, caudate nuclei and occipital cortex as the reference region were delineated from individual magnetic resonance images. The clinical features of the manganism patients still progressed, with increased scores on the Unified Parkinson Disease Rating Scale. The (18)F-AV-133 uptake in the IPD patients decreased at the bilateral striatum, compared with the healthy controls. In the manganism patients, there was no decreased uptake of radioactivity involving the bilateral striatum, except Patient 4, who had a stroke with decreased uptake in the right posterior putamen. The (18)F-AV-133 PET finding reveals that nigrostriatum neurons are not degenerated in chronic manganism and can provide a useful neuroimage biomarker in the differential diagnosis.

Topics: Adrenergic Uptake Inhibitors; Aged; Brain; Case-Control Studies; Dopamine; Female; Fluorine Radioisotopes; Humans; Longitudinal Studies; Male; Manganese Poisoning; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Taiwan; Tetrabenazine; Tomography Scanners, X-Ray Computed

(99m)Tc-TRODAT-1 is the first clinical routine (99m)Tc radiopharmaceutical to evaluate dopamine neurons loss in Parkinson's disease (PD). (18)F-AV-133 is a novel PET radiotracer targeting the vesicular monoamine transporter type 2 (VMAT2) to detect monoaminergic terminal reduction in PD patients. The aim of this study is to compare both images in the same health control (HC) and PD subjects.. Eighteen subjects (8 HC and 10 PD) were recruited for (99m)Tc-TRODAT-1 SPECT, (18)F-AV-133 PET and MRI scans within two weeks. The SPECT images were performed at 4-h post-injection for 45 min, and the PET images were performed at 90 min post-injection for 10 min. Each PET and SPECT image was normalized into Montreal Neurological Institute template aided from individual MRI for comparison. For regional analysis, volume of interest (VOIs) of bilateral caudate nuclei, anterior, posterior putamen and occipital cortex (as reference region) were delineated from the normalized MRI. The specific uptake ratio (SUR) was calculated as (regional mean counts/reference mean counts-1). The nonparametric Mann-Whitney U test was used to evaluate the power of differentiating control from PD subjects for both image modalities. The correlations of the SURs to the clinical parameters were examined. For voxelwise analysis, two-sample t-test for group comparison between HC and PD was computed in both image modalities.. The SURs of caudate nucleus and putamen correlated well between two image modalities (r = 0.81, p<0.001), and showed significant different between HC and PD subjects. Of note, the (18)F-AV-133 SUR displayed a better correlation to PD clinical laterality index as compared to (99m)Tc-TRODAT-1 (r = 0.73 vs. r = 0.33). Voxelwise analysis showed more lesions for PD subjects from (18)F-AV-133 image as compared to (99m)Tc-TRODAT-1 especially at the substantia nigra region.. (18)F-AV-133 PET demonstrated similar performance in differentiation PD from control, and a better correlation to clinical characteristics than that of (99m)Tc-TRODAT-1 SPECT. (18)F-AV-133 PET also showed additional information in substantia nigra integrity in PD subjects by voxelwise analysis. Collectively, (18)F-AV-133 could be a promising and better tracer for clinical use to detect monoaminergic terminal reduction in PD patients.

Topics: Aged; Case-Control Studies; Female; Fluorine Radioisotopes; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Organotechnetium Compounds; Parkinson Disease; Positron-Emission Tomography; Tetrabenazine; Tomography, Emission-Computed, Single-Photon; Tropanes

Currently, diagnosis of Parkinson disease is mainly based on clinical criteria characterized by motor symptoms including bradykinesia, rigidity, resting tremor, and postural instability. Reliable in vivo biomarkers to monitor disease severity and reflect the underlying dopaminergic degeneration are important for future disease-modifying therapy in Parkinson disease.. To use [18F]9-fluoropropyl-(+)-dihydrotetrabenazine (18F-DTBZ; [18F]AV-133) positron emission tomography (PET) to explore the characteristics of vesicular monoamine transporter type 2 imaging in patients with Parkinson disease (PD) with different severity levels as well as to investigate its capability in monitoring clinical severity.. Regional uptakes for 18F-DTBZ PET of different disease stages were measured. Seventeen healthy control participants and 53 patients in 3 groups of mild, moderate, and advanced stages of PD were recruited for 18F-DTBZ PET scans from the Movement Disorders Clinic in the Chang Gung Memorial Hospital, Taiwan.. The severity of disease in patients with PD was quantified by modified Hoehn-Yahr Scale, Unified Parkinson Disease Rating Scale total scores and subscores of posture instability and gait disturbance, tremor, akinesia, and rigidity while not taking medication. Both voxelwise- and volume of interest-based image analyses were performed. The specific uptake ratio (SUR) of each volume of interest and voxel was calculated as (target uptake - reference uptake) / reference uptake using the occipital reference region from magnetic resonance imaging-based spatially normalized 18F-DTBZ images for each participant. Average SUR images were displayed as 2-dimensional and 3-dimensional to illustrate the image patterns in each group. The nonparametric Kruskal-Wallis test on regional SUR was used for group comparison between healthy control participants and patients with PD at different stages. Quantitative parameters were correlated with severity of disease and disease duration by Spearman correlation. Voxelwise analysis for evaluating dopaminergic neuron decline of different PD stages was performed by SPM5.. The 2-dimensional and 3-dimensional 18F-DTBZ PET images demonstrated that the reduction of vesicular monoamine transporter type 2 availability was obviously correlated with the severity of disease in patients with PD. The mean reductions of vesicular monoamine transporter type 2 density for the caudate, putamen,and substantia nigra were 21.50%, 58.20%, and 21.10% for mild PD[Parkinson disease];60.75%, 79.49%,and 39.87%formoderate PD; and63.94%,83.20%, and 44.00% for advanced PD, respectively [corrected]. The SURs of bilateral striatal regions exhibited significantly exponential correlations to stage; disease duration; Unified Parkinson Disease Rating Scale motor score; posture instability and gait disturbance; and akinesia, rigidity, and tremor scores.. In PD, 18F-DTBZ PET is a potential imaging biomarker for measuring dopaminergic degeneration in vivo and monitoring the severity of disease.

Topics: Adult; Aged; Female; Fluorine Radioisotopes; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Muscle Rigidity; Parkinson Disease; Positron-Emission Tomography; Tetrabenazine; Tremor

Mild to moderate Parkinson's disease shows more denervation in the posterodorsal striatum and sparing of the anteroventral striatum. Dopaminergic medications can interfere with anteroventral striatum function by overdosing this relatively intact structure. The authors determined how regional striatal denervation affects medication-associated sequence learning impairment in Parkinson's disease. Eighteen Parkinson's patients performed motor sequence learning on and off levodopa. Patients underwent (11)C-dihydrotetrabenazine positron emission tomography scans to measure nigrostriatal denervation. Patients with more preserved putamen were more likely to exhibit levodopa-associated sequence learning impairments. Furthermore, the ratio of denervation in the anterior to posterior dorsal putamen predicted the level of learning differences on and off levodopa. These results demonstrate that the spatial pattern of nigrostriatal dopaminergic denervation predicts medication responsiveness for motor sequence learning.

Topics: Aged; Antiparkinson Agents; Data Interpretation, Statistical; Denervation; Female; Fluorine Radioisotopes; Humans; Image Processing, Computer-Assisted; Levodopa; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Neostriatum; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Serial Learning; Tetrabenazine

Recently, 9-[(18)F]fluoropropyl-(+)-dihydrotetrabenazine ((18)F-AV-133) was reported as a new vesicular monoamine transporter (VMAT2) imaging agent for diagnosis of Parkinson's disease (PD). To shorten the preparation of (18)F-AV-133 and to make it more widely available, we evaluated a simple, rapid purification with a solid-phase extraction method (SPE) using an Oasis HLB cartridge instead of high pressure liquid chromatography (HPLC). The SPE method produced doses containing a pseudo-carrier, 9-hydroxypropyl-(+)-dihydrotetrabenazine (AV-149).. To test the possible side effects of this pseudo-carrier, comparative dynamic PET scans of the brains of normal monkeys (2 each) and uni-laterally 6-OH-dopamine-lesioned PD monkeys (2 each) were performed using (18)F-AV-133 doses prepared by either SPE (containing pseudo-carrier) or HPLC (containing no pseudo-carrier). Autoradiographs of post mortem monkey brain sections were evaluated to confirm the relative (18)F-AV-133 uptake in the PD monkey brains and the effects of the pseudo-carrier on VMAT2 binding.. The radiochemical purity of the (18)F-AV-133, whether prepared by SPE or by HPLC, was excellent (>99%). PET scans of normal and PD monkey brains showed an expected reduction of VMAT2 in the lesioned areas of the striatum. It was not affected by the presence of the pseudo-carrier, AV-149 (maximally 250 μg/dose). The reduced uptake in the striatum of the lesioned monkey brains was confirmed by autoradiography. Ex vivo inhibition studies of (18)F-AV-133 binding in rat brains, conducted with increasing amounts of AV-149, suggested that at the highest concentration (3.5mg/kg) the VMAT2 binding in the striatum was only moderately blocked (20% reduction).. The pseudo-carrier, AV-149, did not affect the (18)F-AV-133/PET imaging of VMAT2 binding sites in normal or uni-laterally lesioned monkey brains. The new streamlined SPE purification method will enable (18)F-AV-133 to be widely available for routine clinical application in determining changes in monoamine neurons for patient with movement disorders or other psychiatric illnesses.

Topics: Animals; Binding Sites; Biological Transport; Brain; Drug Carriers; Fluorine Radioisotopes; Haplorhini; Humans; Male; Parkinson Disease; Positron-Emission Tomography; Rats; Tetrabenazine; Vesicular Monoamine Transport Proteins

(18)F-9-fluoropropyl-(+)-dihydrotetrabenazine ((18)F-AV-133) is a novel positron emission tomography tracer for imaging the vesicular monoamine transporter II in dopaminergic neuron degeneration, which might be indicative for Parkinson's disease (PD) and other parkinsonism. Studies were performed to optimize the imaging time window for calculating standardized uptake value ratio (SUVR) with correlation to distribution volume ratio (DVR) and in differentiating PD from normal controls (NCs).. Thirteen (18)F-AV-133 positron emission tomography studies were conducted on four NCs (age, 62.3±4.9 years) and nine PD patients (age, 60.8±6.0 years) with Hoehn and Yahr stages 2 to 3. Dynamic images were acquired within 180 min (0-30, 50-140 and 160-180 min) and were rearranged into 14 of 10-min scans. The contralateral striatum was defined as the opposite striatum to the predominantly affected limbs. Volumes of interest (VOIs) of bilateral putamen, caudate nuclei and occipital cortex (OC; as the reference region) were delineated from individual magnetic resonance imaging. SUVRs of striatum to OC were computed from 14 dynamic image sets. The DVRs were computed from Logan graphic analysis by using OC as the input. The performance of SUVR was evaluated based on the correlation of SUVR at each time window to DVR, as well as the Cohen effect size (group mean SUVR difference between PD and NC/standard deviation).. (18)F-AV-133 uptake decreased in PD subjects at bilateral striatum especially at contralateral side with posterior putamen predominant as compared with NC. Consistent higher correlations of SUVRs to DVR for all VOIs were observed at later time window and reached to its maximal value of 0.9917 at 90-100 min. The group mean SUVR differences between NC and PD subjects increased and reached relatively stable values after 90 min. The effect sizes for all VOIs were stable across different time window and with the largest value around 90~120 min.. The scanning time of 90-100 min for (18)F-AV-133 is considered as the optimal time window for summed uptake measurements in terms of SUVRs' correlation to DVRs, differential power, stability and clinical feasibility across and between NC and PD patients.

Topics: Aged; Case-Control Studies; Caudate Nucleus; Female; Fluorine Radioisotopes; Humans; Male; Middle Aged; Occipital Lobe; Parkinson Disease; Positron-Emission Tomography; Putamen; Tetrabenazine; Time Factors; Vesicular Monoamine Transport Proteins

Recently, a PET tracer, 9-[(18)F]fluoropropyl-(+)-dihydrotetrabenazine ([(18)F]AV-133), targeting vesicular monoamine transporter 2 (VMAT2) in the central nervous system has been reported. It is currently under Phase II clinical trials to establish its usefulness in the diagnosis of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. The radiolabeling of [(18)F]AV-133, nucleophilic fluorination reaction and potential effects of pseudo-carrier were evaluated by in vivo biodistribution.. The preparation of [(18)F]AV-133 was evaluated under different conditions, specifically by employing different precursors (-OTs or -Br as the leaving group at the 9-propoxy position), reagents (K222/K(2)CO(3) vs. tributylammonium bicarbonate) and solvents (acetonitrile vs. DMSO), reaction temperature and reaction time. With optimized conditions from these experiments, radiosynthesis and purification with solid-phase extraction (SPE) of [(18)F]AV-133 were performed by an automated nucleophilic [(18)F]fluorination module. In vivo biodistribution in mice on [(18)F]AV-133 purified by either HPLC (no-carrier-added) or the SPE method (containing a pseudo-carrier) was performed and the results compared.. Under a mild fluorination condition (heating at 115 degrees C for 5 min in dimethyl sulfoxide), [(18)F]AV-133 was obtained in a high yield using either -OTs or -Br as the leaving group. However, the -OTs precursor gave better radiochemical yields (>70%, thin layer chromatography analysis) compared to those of the -Br precursor. The optimized reaction conditions were successfully implemented to an automated nucleophilic fluorination module. Labeling and purification of [(18)F]AV133 were readily achieved via this automatic module in good radiochemical yield of 21-41% (n=10) in 40 min. The radiochemical purity was larger than 95%. Biodistribution of SPE-purified product (containing a pseudo-carrier) in mice showed a high striatum/cerebellum ratio (4.18+/-0.51), which was comparable to that of HPLC-purified [(18)F]AV-133 (4.51+/-0.10).. The formation of [(18)F]AV-133 was evaluated under different labeling conditions. These improved labeling conditions and SPE purification were successfully implemented into an automated synthesis module. This offers a short preparation time (about 40 min), simplicity in operation and ready applicability for routine clinical operation.

Topics: Animals; Biological Transport; Fluorine Radioisotopes; Halogenation; Male; Mice; Neostriatum; Parkinson Disease; Positron-Emission Tomography; Solid Phase Extraction; Tetrabenazine; Tissue Distribution; Vesicular Monoamine Transport Proteins

The utility of [(18)F]FPBM [2-(2'-((dimethylamino)methyl)-4'-(3-[(18)F]-fluoropropoxy)phenylthio)benzenamine], a selective serotonin transporter (SERT) tracer, and [(18)F]AV-133 [(+)-2-Hydroxy-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-1,2,3,4,6,7-hexahydro-11bH-benzo[a]quinolizine], a selective vesicular monoamine transporter 2 (VMAT2) tracer, were tested in the 6-hydroxydopamine (6-OHDA) unilateral lesioned rat model.. Positron emission tomography (PET) imaging of three 6-OHDA unilateral lesioned male Sprague Dawley rats (Rats 1-3) were performed with [(18)F]FPBM and [(18)F]AV-133 to examine whether changes in SERT and VMAT2 binding, respectively, could be detected in the brain. The brains of the three rats were then removed and examined by in vitro autoradiography with [(18)F]FPBM and the dopamine transporter ligand, [(125)I]IPT [N-(3'-[(125)I]-iodopropen-2'-yl)-2-beta-carbomethoxy-3-beta-(4-chloro phenyl) tropane, for confirmation. Biodistribution of [(18)F]FPBM in a separate group of p-chloroamphetamine (PCA) treated rats were also performed.. PET image analysis showed varying levels of SERT binding reduction (Rat 1=-11%, Rat 2=-4%, Rat 3=-43%; n=2) and a clear and definitive loss of VMAT2 binding (Rat 1=-87%, Rat 2=-72%, and Rat 3=-91%; n=1) in the left striatum when compared to the right (non-lesioned side) striatum. The results from PET imaging were corroborated with quantitative in vitro autoradiography. Rats treated with a selective serotonin toxin (p-chloroamphetamine) showed a significant reduction of [(18)F]FPBM uptake in the cortex and hypothalamus regions of the brain.. The preliminary data suggest that [(18)F]FPBM and [(18)F]AV-133 may be useful for the examination of serotonergic and dopaminergic neuron integrity, respectively, in the living brain.

Topics: Aniline Compounds; Animals; Autoradiography; Disease Models, Animal; Fluorine Radioisotopes; Male; p-Chloroamphetamine; Parkinson Disease; Positron-Emission Tomography; Protein Binding; Radioactive Tracers; Rats; Rats, Sprague-Dawley; Serotonin Plasma Membrane Transport Proteins; Substrate Specificity; Tetrabenazine; Vesicular Monoamine Transport Proteins