Neurofunctional imaging of the pancreas utilizing the cholinergic PET radioligand [ 18 F]4-fluorobenzyltrozamicol

Clark, Paige B.; Gage, H. Donald; Brown-Proctor, Clive; Buchheimer, Nancy; Callés-Escandon, Jorge; Mach, Robert H.; Morton, Kathryn A.

doi:10.1007/s00259-003-1350-7

Cited by 29 publications

(25 citation statements)

References 10 publications

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“…Imaging of brown adipose tissue, lung, and pancreas present unique and formidable challenges because of problems in localization and signal identification for brown adipose tissue (3), low in vivo tissue density hindering acquisition of high-contrast images for lung (21), and nonpancreatic abdominal uptake causing poor signalto-noise ratios for pancreas (39). Recent use of 18 F-FDG in full-body scanning has revealed anomalous tracer uptake in areas of supraclavicular fat (40), suggesting that isolation of brown adipose tissue in large mammals may be possible.…”

Section: Discussionmentioning

confidence: 99%

Presence of Specific 11C-meta-Hydroxyephedrine Retention in Heart, Lung, Pancreas, and Brown Adipose Tissue

Thackeray¹,

Beanlands²,

DaSilva³

2007

Journal of Nuclear Medicine

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11 C-meta-Hydroxyephedrine (HED) is used in cardiac PET as an index of norepinephrine (NE) reuptake transporter (NET) density and synaptic NE levels. Whereas cardiac uptake is well documented, tracer retention in other tissues with rich noradrenergic innervation is unclear. Dysfunctional sympathetic nervous system (SNS) function in extracardiac metabolic storage tissues (i.e., adipose tissue and skeletal muscle) and endocrine organs contributes to several disorders. The aim of this study was to determine the potential of HED as an index of NE function in brown adipose tissue, lung, pancreas, skeletal muscle, and kidney by identifying NET-specific retention and determining the presence of radiolabeled metabolites. Methods: Male Sprague-Dawley rats were administered HED and sacrificed at 30 min after tracer injection. Tissues were rapidly excised and counted for radioactivity, and relative tracer retention was quantified. Pretreatment with NET inhibitors established specific HED accumulation. The effect of elevated NE was tested by subcutaneous minipump NE infusion or inhibition of monoamine oxidase. Column-switch high-performance liquid chromatography (HPLC) was used to analyze the presence of radiolabeled metabolites in heart, brown adipose tissue, pancreas, and plasma. Results: NET-specific retention was observed in heart, brown adipose tissue, lung, and pancreas but not in liver, skeletal muscle, or kidney. A dosedependent response of HED accumulation to treatments elevating NE levels was established in tissues exhibiting specific uptake. At 30 min after tracer administration, HPLC analysis revealed 93%-95% of total radioactivity signal derived from unchanged HED in heart, pancreas, and brown adipose tissue compared with 61% 6 8% unchanged HED in plasma. Conclusion: In addition to the heart, lung, pancreas, and brown adipose tissue exhibit specific and NE-responsive uptake of HED, supporting the potential for novel PET studies of SNS integrity in these tissues.Key Words: sympathetic nervous system function; norepinephrine transporter uptake-1; competition with norepinephrine; HPLC column-switch system The sympathetic nervous system (SNS) is a primary extrinsic control mechanism mediating cardiac function, metabolic processes, and adaptation to stress. In normal conditions, the neurotransmitter norepinephrine (NE) is released from the presynaptic bouton into the synapse, where it binds to and stimulates adrenoceptors on pre-and postsynaptic cells. Excess NE is recycled into the presynaptic neuron by active transport via the uptake-1 NE reuptake transporter (NET) (1,2).In myocardium, the SNS modulates heart rate, cardiac output, and stroke volume (2). In metabolic storage tissues, SNS activation stimulates 2 key processes: lipolysis-the breakdown of lipids primarily in white adipocytes-and thermogenesis-the uncoupling of mitochondrial energetics promoting heat release over energy storage, primarily in brown adipocytes and skeletal muscle (3). The SNS also partially controls pancreatic secretion of insulin and gl...

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Section: Discussionmentioning

confidence: 99%

Presence of Specific 11C-meta-Hydroxyephedrine Retention in Heart, Lung, Pancreas, and Brown Adipose Tissue

Thackeray¹,

Beanlands²,

DaSilva³

2007

Journal of Nuclear Medicine

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“…Clark et al [5] demonstrated that the body of the pancreas can be imaged with fluorine-18 4-fluorobenzyltrozamicol, a radioligand that binds to specific neuroreceptors (vesicular acetylcholine transporters) that are present on presynaptic vesicles in neurons innervating the pancreas. Similarly, taking advantage of bicarbonate and/or organic anion transporters expressed by pancreatic acinar cells, [ 11 C]acetate has been used to visualize the exocrine pancreas [6,7].…”

Section: Introductionmentioning

confidence: 99%

Visualizing pancreatic β-cell mass with [11C]DTBZ

Simpson

Souza

Witkowski

et al. 2006

Nuclear Medicine and Biology

109

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Abstractβ-Cell mass (BCM) influences the total amount of insulin secreted, varies by individual and by the degree of insulin resistance, and is affected by physiologic and pathologic conditions. The islets of Langerhans, however, appear to have a reserve capacity of insulin secretion and, overall, assessments of insulin and blood glucose levels remain poor measures of BCM, β-cell function and progression of diabetes. Thus, novel noninvasive determinations of BCM are needed to provide a quantitative endpoint for novel therapies of diabetes, islet regeneration and transplantation. Built on previous gene expression studies, we tested the hypothesis that the targeting of vesicular monoamine transporter 2 (VMAT2), which is expressed by β cells, with [ 11 C]dihydrotetrabenazine ([ 11 C]DTBZ), a radioligand specific for VMAT2, and the use of positron emission tomography (PET) can provide a measure of BCM. In this report, we demonstrate decreased radioligand uptake within the pancreas of Lewis rats with streptozotocininduced diabetes relative to their euglycemic historical controls. These studies suggest that quantitation of VMAT2 expression in β cells with the use of [ 11 C]DTBZ and PET represents a method for noninvasive longitudinal estimates of changes in BCM that may be useful in the study and treatment of diabetes.

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“…Fluorine-18 4-fluorobenzyltrozamicol binds to the vesicular acetylcholine transporter that is present on presynaptic vesicles in the neurons innervating the pancreas and can be used to image the body of the pancreas (14). Similarly, taking advantage of the bicarbonate and/or organic anion transporters expressed by pancreatic acinar cells, [ 11 C]acetate has been used to visualize the exocrine pancreas (15,16).…”

Section: Introductionmentioning

confidence: 99%

Longitudinal noninvasive PET-based cell mass estimates in a spontaneous diabetes rat model

Souza¹

2006

Journal of Clinical Investigation

134

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Neurofunctional imaging of the pancreas utilizing the cholinergic PET radioligand [ 18 F]4-fluorobenzyltrozamicol

Cited by 29 publications

References 10 publications

Presence of Specific 11C-meta-Hydroxyephedrine Retention in Heart, Lung, Pancreas, and Brown Adipose Tissue

Presence of Specific 11C-meta-Hydroxyephedrine Retention in Heart, Lung, Pancreas, and Brown Adipose Tissue

Visualizing pancreatic β-cell mass with [11C]DTBZ

Longitudinal noninvasive PET-based cell mass estimates in a spontaneous diabetes rat model

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