Showing papers by "Ronald J. Voll published in 2003"
TL;DR: An improved synthesis of the precursor of anti-[18F]FACBC has been devised which demonstrates high stereoselectivity and suitability for large-scale preparations, and the major non-radioactive species present in doses of anti- 1-amino-3-hydroxycyclobutane-1-carboxylic acid has been identified.
106 citations
Journal Article•
TL;DR: In this article, an initial assessment of the usefulness of 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-18F-fluoroethyl)nortropane (18F -FECNT) PET scanning in determining in vivo brain dopamine transporter (DAT) density in healthy humans and subjects with Parkinson's disease (PD).
Abstract: The aim of this study was to do an initial assessment of the usefulness of 2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-18F-fluoroethyl)nortropane (18F-FECNT) PET scanning in determining in vivo brain dopamine transporter (DAT) density in healthy humans and subjects with Parkinson’s disease (PD). Methods: We investigated 6 neurologically healthy subjects and 5 PD patients: 2 with mild unilateral disease, 1 with mild-to-moderate bilateral disease, and 2 with moderately severe bilateral disease. The healthy subjects underwent a 3-h PET scan (26 frames) and the PD subjects underwent a 2-h PET scan (23 frames) while 18F-FECNT was being injected over the first 5 min of the scan. Arterial blood samples were taken throughout scanning for well-counter and metabolite analysis to determine the presence of possible active metabolites. The scans were reconstructed; then we placed spheric regions of interest in the caudate nuclei, putamena, thalami, brain stem, cerebellum, and occipital cortex of each subject. The radioactivity level in each region was calculated for each frame of a subject’s PET scan. Then we calculated target tissue-to-cerebellum ratios for each time frame. Results: The analysis of arterial blood samples revealed that metabolism of the tracer was rapid. The ether-extractable component of the arterial input was >98% pure 18F-FECNT. The caudate nucleus and putamen exhibited the highest uptake and prolonged retention of the radioligand. They both attained maximum uptake at ∼90 min, with the healthy subjects’ average caudate- and putamen-to-cerebellum ratios (±SD) at that time being 9.0 ± 1.2 and 7.8 ± 0.7, respectively. The maximal caudate-to-cerebellum ratios for the healthy subjects ranged from 7.6 to 10.5 and their maximal putamen-to-cerebellum ratios ranged from 7.1 to 9.3. The 2 early-stage, unilateral PD patients had, at 90 min, an average right caudate-to-cerebellum ratio of 5.3 ± 1.1 and a left ratio of 5.9 ± 0.7 and an average right putamen-to cerebellum ratio of 2.8 ± 0.1 and a left ratio of 3.0 ± 0.6. The late-stage PD patients had, at 90 min, an average right caudate-to-cerebellum ratio of 3.7 ± 0.4 and a left ratio of 3.9 ± 0 and an average right putamen-to cerebellum ratio of 1.8 ± 0.1 and a left ratio of 1.8 ± 0. Conclusion: These results indicate that 18F-FECNT is an excellent candidate radioligand for in vivo imaging of the DAT system in humans. It has a much higher affinity for DAT than for the serotonin transporter and yields the highest peak striatum-to-cerebellum ratios and has among the most favorable kinetics of 18F-radiolabeled DAT ligands. Having picked up presymptomatic changes in the hemisphere opposite the unaffected side of the body in our early-stage (unilateral) PD patients, it appears that, like other DAT radioligands, it may be able to identify presymptomatic PD.
72 citations
TL;DR: In vitro experiments indicate that DAT is trafficked into the cell by isoflurane without changing the total amount of DAT in the striatum, and the PET data are consistent with this finding, provided that intracellular DAT acquires a conformation that has low affinity for [18F]FECNT.
Abstract: BackgroundIsoflurane administration is known to increase extracellular dopamine (DA) concentration Because the dopamine transporter (DAT) is a key regulator of DA, it is likely affected by isoflurane This study investigates the hypothesis that isoflurane inhibits DA reuptake by causing DAT to be t
60 citations
TL;DR: The PET measured BP of [18F]FECNT increased by 50% and 45% during the phenylephrine and norepinephrine infusion, respectively, and the immunohistochemistry and immunoblot analyses did not show a difference in total DAT.
Abstract: PURPOSE: 8-(2-[18F]fluoroethyl)-2β-carbomethoxy-3β-(4-chlorophenyl)nortropane ([18F]FECNT) is a radiotracer for positron emission tomography (PET) used to trace the location and binding potential (BP) of the dopamine transporter (DAT). We tested the hypothesis that adrenergic receptor agonists increase the BP of [18F]FECNT for the DAT. PROCEDURES: Anesthetized monkeys were scanned twice to determine the ligand BP at baseline and during administration of phenylephrine (3–6 μg/kg/min) or norepinephrine (0.5–1 μg/kg/min). Standard immunohistochemistry and immunoblot analyses were performed in rats to determine if the quantity of DAT changed with phenylephrine. [18F]FECNT uptake in human embryonic kidney (HEK) cells, stably transfected with DAT cDNA, was measured by gamma scintillation counting during phenylephrine. RESULTS: The PET measured BP of [18F]FECNT increased by 50% and 45% during the phenylephrine and norepinephrine infusion, respectively. The immunohistochemistry and immunoblot analyses did not show a difference in total DAT. CONCLUSION: Adrenergic agonists increase the BP of [18F]FECNT in monkey striatum.
3 citations