scholarly journals Evaluation of Dopaminergic Presynaptic Integrity: 6-[18F]Fluoro-L-Dopa Versus 6-[18F]Fluoro-L-m-Tyrosine

1999 ◽  
Vol 19 (3) ◽  
pp. 278-287 ◽  
Author(s):  
D. J. Doudet ◽  
G. L.-Y. Chan ◽  
S. Jivan ◽  
O. T. DeJesus ◽  
E. G. McGeer ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Metabolic Pathway ◽  
Arterial Input Function ◽  
Occipital Cortex ◽  
Input Function ◽  
Emission Tomography ◽  
Dopa Decarboxylase ◽  
Positron Emission ◽  
Pet Scans

The effectiveness of 6-[18F]fluoro-L- m-tyrosine (6FMT) to evaluate dopamine presynaptic integrity was compared to that of 6-[18F]fluoro-L-dopa (6FDOPA) in vivo by positron emission tomography (PET). Six normal and six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -lesioned monkeys received 6FDOPA and 6FMT PET scans on separate occasions with identical scanning protocols. Four measures, the rate of uptake of tracer into striatum using either the arterial input function ( Ki) or the activity in the occipital cortex as the input function ( Kc), the rate of loss of striatal radioactivity ( kloss), and an index of “effective turnover” of dopamine ( kloss/ Ki), were obtained for both tracers during extended PET studies. 6-[18F]Fluoro-L- m-tyrosine was as effective as 6FDOPA in separating normals from MPTP-lesioned subjects on the basis of the uptake rate constants Ki and Kc. However, in contrast to 6FDOPA, it was not possible to differentiate the normal from the lesioned animal using kloss or kloss/ Ki for 6FMT. Thus, FMT appears to be a reasonable, highly specific tracer for studying the activity of aromatic dopa decarboxylase enzyme as an index of presynaptic integrity. However, if one is interested in investigating further the metabolic pathway and obtaining an in vivo estimate of the effective turnover of dopamine (after pharmacologic manipulation, for example), 6FDOPA remains the tracer of choice.

scholarly journals In vivo Serotonin-Sensitive Binding of [11C]CUMI-101: A Serotonin 1A Receptor Agonist Positron Emission Tomography Radiotracer

2010 ◽  
Vol 31 (1) ◽  
pp. 243-249 ◽  
Author(s):  
Matthew S Milak ◽  
Alin J Severance ◽  
Jaya Prabhakaran ◽  
JS Dileep Kumar ◽  
Vattoly J Majo ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Arterial Input Function ◽  
Input Function ◽  
Emission Tomography ◽  
Binding Potential ◽  
Papio Anubis ◽  
Positron Emission ◽  
Future Work ◽  
G Protein Coupled

Positron emission tomography studies of 5-hydroxytryptamine (5-HT)1A receptors have hitherto been limited to antagonist radiotracers. Antagonists do not distinguish high/low-affinity conformations of G protein-coupled receptors and are less likely to be sensitive to intrasynaptic serotonin levels. We developed a novel 5-HT1A agonist radiotracer [11C]CUMI-101. This study evaluates the sensitivity of [11C]CUMI-101 binding to increases in intrasynaptic serotonin induced by intravenous citalopram and fenfluramine. Two Papio anubis were scanned, using [11C]CUMI-101 intravenous bolus of 4.5±1.5 mCi. Binding potential (BPF= Bavail/ KD) was measured before ( n=10) and 20 minutes after elevation of intrasynaptic serotonin by intravenous citalopram (2 mg/kg, n=3; 4 mg/kg, n=3) and fenfluramine (2.5 mg/kg, n=3) using a metabolite-corrected arterial input function. Occupancy was also estimated by the Lassen graphical approach. Both citalopram and fenfluramine effects were significant for BPF ( P=0.031, P=0.049, respectively). The Lassen approach estimated 15.0, 30.4, and 23.7% average occupancy after citalopram 2 mg/kg, 4 mg/kg, and fenfluramine 2.5 mg/kg, respectively. [11C]CUMI-101 binding is sensitive to a large increase in intrasynaptic serotonin in response to robust pharmacological challenges. These modest changes in BPF may make it unlikely that this ligand will detect changes in intrasynaptic 5-HT under physiologic conditions; future work will focus on evaluating its utility in measuring the responsiveness of the 5-HT system to pharmacological challenges.

scholarly journals Imaging the GABA-Benzodiazepine Receptor Subtype Containing the α5-Subunit In Vivo with [11C]Ro15 4513 Positron Emission Tomography

2002 ◽  
Vol 22 (7) ◽  
pp. 878-889 ◽  
Author(s):  
Anne Lingford-Hughes ◽  
Susan P. Hume ◽  
Adrian Feeney ◽  
Ella Hirani ◽  
Safiye Osman ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Benzodiazepine Receptors ◽  
Benzodiazepine Receptor ◽  
Occipital Cortex ◽  
Input Function ◽  
Emission Tomography ◽  
Receptor Subtype ◽  
Receptor Localization ◽  
Positron Emission

There is evidence of marked variation in the brain distribution of specific subtypes of the GABA-benzodiazepine receptor and that particular subtypes mediate different functions. The α5-containing subtype is highly expressed in the hippocampus, and selective α5 inverse agonists (which decrease tonic GABA inhibition) are being developed as potential memory-enhancing agents. Evidence for such receptor localization and specialization in humans in vivo is lacking because the widely used probes for imaging the GABA-benzodiazepine receptors, [11C]flumazenil and [123I]iomazenil, appear to reflect binding to the α1 subtype, based on its distribution and affinity of flumazenil for this subtype. The authors characterized for positron emission tomography (PET) a radioligand from Ro15 4513, the binding of which has a marked limbic distribution in the rat and human brain in vivo. Competition studies in vivo in the rat revealed that radiolabeled Ro15 4513 uptake was reduced to nonspecific levels only by drugs that have affinity for the α5 subtype (flunitrazepam, RY80, Ro15 4513, L655,708), but not by the α1 selective agonist, zolpidem. Quantification of [11C]Ro15 4513 PET was performed in humans using a metabolite-corrected plasma input function. [11C]Ro15 4513 uptake was relatively greater in limbic areas compared with [11C]flumazenil, but lower in the occipital cortex and cerebellum. The authors conclude that [11C]Ro15 4513 PET labels in vivo the GABA-benzodiazepine receptor containing the α5 subtype in limbic structures and can be used to further explore the functional role of this subtype in humans.

scholarly journals Human Striatal l-DOPA Decarboxylase Activity Estimated in vivo Using 6-[18F]fluoro-DOPA and Positron Emission Tomography: Error Analysis and Application to Normal Subjects

1993 ◽  
Vol 13 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Hiroto Kuwabara ◽  
Paul Cumming ◽  
Jakob Reith ◽  
Gabriel Léger ◽  
Mirko Diksic ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Error Analysis ◽  
Frontal Cortex ◽  
Transport Coefficients ◽  
Fixed Ratio ◽  
Emission Tomography ◽  
Dopa Decarboxylase ◽  
Decarboxylase Activity ◽  
Positron Emission

DOPA decarboxylase is the enzyme directly responsible for the synthesis of the neurotransmitters dopamine and serotonin, and indirectly of noradrenaline, in brain. We used the decarboxylation coefficient ( kD3) of 6-[18F]fluoro-DOPA (FDOPA) to denote the relative activity of l-DOPA decarboxylase in vivo in the human brain. To determine the relative enzyme activity with positron emission tomography (PET), we evaluated the model that separates the metabolism into compartments of nondiffusible and diffusible (i.e., transient) tracer metabolites. Error analysis indicated that the least-squares optimization alone was not sufficient to yield accurate estimates of kD3 in the presence of the inherent error of PET. To improve the accuracy of the kD3 estimates by optimizing the number of parameters, we introduced biological constraints which included a tracer partition volume ( Ve) common to frontal cortex and striatum, and a fixed ratio ( q) between the blood–brain barrier transport coefficients of O-methyl-[18F]fluoro-DOPA and FDOPA, the two sources of radioactivity in plasma. We found that a two-step analysis yielded sufficiently accurate estimates of kD3. The two steps include the initial estimation of the partition volume in frontal cortex and the subsequent use of this value to determine kD3 in striatum and other structures. We studied twelve healthy controls (age 45 ± 15 years). The average kD3 value was 0.081 ± 0.024 min−1 (coefficient of variation (COV) 30%) for caudate nucleus, 0.074 ± 0.013 min“1 (COV 18%) for putamen, and 0.010 ± 0.005 min−1 (COV 50%) for cerebral cortex.

In Vivo Treatment Sensitivity Testing With Positron Emission Tomography/Computed Tomography After One Cycle of Chemotherapy for Hodgkin Lymphoma

2014 ◽  
Vol 32 (25) ◽  
pp. 2705-2711 ◽  
Author(s):  
Martin Hutchings ◽  
Lale Kostakoglu ◽  
Jan Maciej Zaucha ◽  
Bogdan Malkowski ◽  
Alberto Biggi ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Positron Emission Tomography ◽  
Hodgkin Lymphoma ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Emission Tomography ◽  
Sensitivity Testing ◽  
Positron Emission ◽  
Pet Scans

Purpose Negative [18F]fluorodeoxyglucose (FDG) –positron emission tomography (PET)/computed tomography (CT) after two cycles of chemotherapy indicates a favorable prognosis in Hodgkin lymphoma (HL). We hypothesized that the negative predictive value would be even higher in patients responding rapidly enough to be PET negative after one cycle. This prospective study aimed to assess the prognostic value of PET after one cycle of chemotherapy in HL and to assess the dynamics of FDG uptake after one cycle (PET1) and after two cycles (PET2). Patients and Methods All PET scans were read by two blinded, independent reviewers in different countries, according to the Deauville five-point scale. The main end point was progression-free survival (PFS) after 2 years. Results A total of 126 patients were included, and all had PET1; 89 patients had both PET1 and PET2. The prognostic value of PET1 was statistically significant with respect to both PFS and overall survival. Two-year PFS for PET1-negative and PET1-positive patients was 94.1% and 40.8%, respectively. Among those with both PET1 and PET2, 2-year PFS was 98.3% and 38.5% for PET1-negative and PET1-positive patients and 90.2% and 23.1% for PET2-negative and PET2-positive patients, respectively. No PET1-negative patient was PET2 positive. Conclusion PET after one cycle of chemotherapy is highly prognostic in HL. No other prognostic tool identifies a group of patients with HL with a more favorable outcome than those patients with a negative PET1. In the absence of precise pretherapeutic predictive markers, PET1 is the best method for response-adapted strategies designed to select patients for less intensive treatment.

scholarly journals Imaging Cortical Dopamine D1 Receptors Using [11C]NNC112 and Ketanserin Blockade of the 5-HT2A Receptors

2009 ◽  
Vol 30 (5) ◽  
pp. 985-993 ◽  
Author(s):  
Ana M Catafau ◽  
Graham E Searle ◽  
Santiago Bullich ◽  
Roger N Gunn ◽  
Eugenii A Rabiner ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Emission Tomography ◽  
D1 Receptors ◽  
Lower Amount ◽  
Quantification Method ◽  
Positron Emission ◽  
Selective Ligands ◽  
Pet Scans

[11C]NNC112 (8-chloro-7-hydroxy-3-methyl-5-(7-benzofuranyl)-2,3,4,5-tetrahydro-IH-3-benzazepine), a selective positron-emission tomography (PET) ligand for the D1 receptor (R) over the 5-HT2A R in vitro, has shown lower selectivity in vivo, hampering measurement of D1 R in the cortex. [11C]NNC112 PET and intravenous (i.v) ketanserin challenge were used to (1) confirm the previous findings of [11C]NNC112 in vivo D1 R selectivity, and (2) develop a feasible methodology for imaging cortical D1 R without contamination by 5-HT2A R. Seven healthy volunteers underwent [11C]NNC112 PET scans at baseline and after a 5-HT2A R-blocking dose of ketanserin (0.15 mg/kg, i.v.). Percent BPND change between the post-ketanserin and baseline scans was calculated. Irrespective of the quantification method used, ketanserin pretreatment led to significant decrease of BPND in the cortical (∼30%) and limbic regions (∼20%) but not in the striatum, which contains a much lower amount of 5-HT2A R. Therefore, ketanserin allows D1 R signal to be detected by [11C]NNC112 PET without significant 5-HT2A R contamination. These data confirm the presence of a significant 5-HT2A R contribution to cortical [11C]NNC112 signal, and call for caution in the interpretation of published [11C]NNC112 PET findings on cortical D1 R in humans. In the absence of more selective ligands, [11C]NNC112 PET with ketanserin can be used for cortical D1 R imaging in vivo.

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