Unknown

Dataset Information

0

[(11)C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain.


ABSTRACT: 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.

SUBMITTER: Visser AK 

PROVIDER: S-EPMC3887351 | biostudies-other | 2014 Jan

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC4927617 | biostudies-other
| S-EPMC4161128 | biostudies-literature
| S-EPMC9710165 | biostudies-literature
| S-EPMC8584019 | biostudies-literature
| S-EPMC5980101 | biostudies-literature
| S-EPMC9330595 | biostudies-literature
| S-EPMC9146140 | biostudies-literature
| S-EPMC6277573 | biostudies-literature
| S-EPMC4011360 | biostudies-other
| S-EPMC7576622 | biostudies-literature