Development of a reliable remote-controlled synthesis ofβ-[11C]-5-hydroxy-L-tryptophan on a Zymark robotic system

Neels, Oliver; Jager, Pieter L.; Koopmans, Klaas Pieter; Eriks, E.; Vries, de Elisabeth G. E.; Kema, Ido P.; Elsinga, Philippus

doi:10.1002/jlcr.1110

Cited by 18 publications

(12 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 18 F]FDOPA at 0.19 F 0.01 mL, corresponding to a dose of 6.17 F 0.63 MBq, was injected per animal. [ 11 C]HTP was synthesized via an enzymatic method with an average specific activity of 30,000 GBq/mmol after end of synthesis as recently described (16). It was used at a concentration of f0.67 nmol/mL.…”

Section: Methodsmentioning

confidence: 99%

Manipulation of [11C]-5-Hydroxytryptophan and 6-[18F]Fluoro-3,4-Dihydroxy-l-Phenylalanine Accumulation in Neuroendocrine Tumor Cells

Neels¹,

Koopmans²,

Jager³

et al. 2008

Cancer Research

View full text Add to dashboard Cite

Section: Methodsmentioning

confidence: 99%

Manipulation of [11C]-5-Hydroxytryptophan and 6-[18F]Fluoro-3,4-Dihydroxy-l-Phenylalanine Accumulation in Neuroendocrine Tumor Cells

Neels¹,

Koopmans²,

Jager³

et al. 2008

Cancer Research

View full text Add to dashboard Cite

“…As outlined above, more research has been done with [ 11 C]AMT than with [ 11 C]5-HTP, probably because producing [ 11 C]5-HTP is difficult, requiring several enzymatic steps [ 110 ]. At the moment it is only produced in four to five centres all over the world.…”

Section: Discussionmentioning

confidence: 99%

Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications

Visser

Waarde

Willemsen

et al. 2010

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

The serotonergic system of the brain is complex, with an extensive innervation pattern covering all brain regions and endowed with at least 15 different receptors (each with their particular distribution patterns), specific reuptake mechanisms and synthetic processes. Many aspects of the functioning of the serotonergic system are still unclear, partially because of the difficulty of measuring physiological processes in the living brain. In this review we give an overview of the conventional methods of measuring serotonin synthesis and methods using positron emission tomography (PET) tracers, more specifically with respect to serotonergic function in affective disorders. Conventional methods are invasive and do not directly measure synthesis rates. Although they may give insight into turnover rates, a more direct measurement may be preferred. PET is a noninvasive technique which can trace metabolic processes, like serotonin synthesis. Tracers developed for this purpose are α-[11C]methyltryptophan ([11C]AMT) and 5-hydroxy-L-[β-11C]tryptophan ([11C]5-HTP). Both tracers have advantages and disadvantages. [11C]AMT can enter the kynurenine pathway under inflammatory conditions (and thus provide a false signal), but this tracer has been used in many studies leading to novel insights regarding antidepressant action. [11C]5-HTP is difficult to produce, but trapping of this compound may better represent serotonin synthesis. AMT and 5-HTP kinetics are differently affected by tryptophan depletion and changes of mood. This may indicate that both tracers are associated with different enzymatic processes. In conclusion, PET with radiolabelled substrates for the serotonergic pathway is the only direct way to detect changes of serotonin synthesis in the living brain.

show abstract

“…Tracer and Drug Treatment [ 11 C]5-HTP was produced according to a published method. 22 The average injected dose of [ 11 C]5-HTP was 12.0 ± 6.4 MBq with a specific radioactivity of 23.4±11.2 GBq/mmoL. All drugs were administered by i.p.…”

Section: Materials and Methods Animalsmentioning

confidence: 99%

“…Another option to measure 5-HT synthesis with PET, is labeling the endogenous precursor of serotonin, [ 11 C]5-HTP. 21,22 A great advantage of this compound is that it is metabolized exactly in the same way as endogenous 5-HTP. Several studies with [ 11 C]5-HTP have indicated that this tracer can be used to measure 5-HT synthesis rates by kinetic modeling of PET data.…”

Section: Introductionmentioning

confidence: 99%

[¹¹C]5-HTP and microPET are Not Suitable for Pharmacodynamic Studies in the Rodent Brain

Visser

Ramakrishnan

Willemsen

et al. 2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

The PET tracer [(11)C]5-hydroxytryptophan ([(11)C]5-HTP), which is converted to [(11)C]5-hydroxytryptamine ([(11)C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [(11)C]5-HTP in rat? Male rats were scanned with [(11)C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [(11)C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [(11)C]5-HTP uptake, and the k3. This was unexpected as NSD 1015 directly inhibits the enzyme converting [(11)C]5-HTP to [(11)C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [(11)C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.

show abstract

Development of a reliable remote-controlled synthesis ofβ-[11C]-5-hydroxy-L-tryptophan on a Zymark robotic system

Abstract: SummaryPrecise staging of neuroendocrine tumors (NET) using positron emission tomography (PET) tracers visualizing their specific metabolic activity is of interest. Besides

Cited by 18 publications

References 12 publications

Manipulation of [11C]-5-Hydroxytryptophan and 6-[18F]Fluoro-3,4-Dihydroxy-l-Phenylalanine Accumulation in Neuroendocrine Tumor Cells

Manipulation of [11C]-5-Hydroxytryptophan and 6-[18F]Fluoro-3,4-Dihydroxy-l-Phenylalanine Accumulation in Neuroendocrine Tumor Cells

Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications

[¹¹C]5-HTP and microPET are Not Suitable for Pharmacodynamic Studies in the Rodent Brain

Contact Info

Product

Resources

About

Development of a reliable remote-controlled synthesis ofβ-[11C]-5-hydroxy-L-tryptophan on a Zymark robotic system

Abstract: SummaryPrecise staging of neuroendocrine tumors (NET) using positron emission tomography (PET) tracers visualizing their specific metabolic activity is of interest. Besides

Cited by 18 publications

References 12 publications

Manipulation of [11C]-5-Hydroxytryptophan and 6-[18F]Fluoro-3,4-Dihydroxy-l-Phenylalanine Accumulation in Neuroendocrine Tumor Cells

Manipulation of [11C]-5-Hydroxytryptophan and 6-[18F]Fluoro-3,4-Dihydroxy-l-Phenylalanine Accumulation in Neuroendocrine Tumor Cells

Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications

[11C]5-HTP and microPET are Not Suitable for Pharmacodynamic Studies in the Rodent Brain

Contact Info

Product

Resources

About

[¹¹C]5-HTP and microPET are Not Suitable for Pharmacodynamic Studies in the Rodent Brain