Published November 2019 | Version v1
Journal article Metadata-only

Radiolabeling and in vivo evaluation of [11C]AGH-44. A potential lead structure to develop a positron emission tomography radioligand for the 5-HT7 receptor

Creators

  • 1. Skanes University Hospital, Lund (Sweden). Radiation Physics, Nuclear Medicine Physics Unit
  • 2. University of Copenhagen, Copenhagen (Denmark). Department for Drug Design and Pharmacology, Faculty of Health and Medical Sciences
  • 3. Rigshospitalet, Copenhagen (Denmark). Neurobiology Research Unit
  • 4. University of Copenhagen, Copenhagen (Denmark). Cluster for Molecular Imaging, Faculty of Health Science
  • 5. University Hospital Copenhagen, Copenhagen (Denmark). Department of Clinical Physiology, Nuclear Medicine and PET
  • 6. Polish Academy of Sciences, Krakow (Poland). Institute of Pharmacology

Description

AGH-44 is described as a selective low-basicity serotonin 7 receptor (5-HT7R) agonist. In this paper, we evaluate if AGH-44 can act as a lead structure to develop a 5-HT7R selective positron emission tomography (PET) tracer. 11C-labeling of AGH-44 succeeded in a two-step, one-pot procedure in good yields. Subsequent PET studies showed that [11C]AGH-44 displays low blood-brain-barrier passage in Long-Evans rats. Moreover, [11C]AGH-44 brain accumulation showed to be independent on permeability glycoprotein (P-gp) efflux inhibition. Results from biodistribution and metabolism studies could neither explain the observed low brain uptake. As such, we believe that this scaffold is not an optimal starting point to develop a 5-HT7R selective PET tracer. (author)

Additional details

Publishing Information

Journal Title
Journal of Radioanalytical and Nuclear Chemistry
Journal Volume
322
Journal Issue
2
Journal Page Range
p. 847-851
ISSN
0236-5731
CODEN
JRNCDM

INIS

Country of Publication
Hungary
Country of Input or Organization
Hungary
INIS RN
51005939
Subject category
S60: APPLIED LIFE SCIENCES;
Descriptors DEI
BLOOD-BRAIN BARRIER; CARBON 11; LABELLING; POSITRON COMPUTED TOMOGRAPHY; RATS; RECEPTORS; SEROTONIN; TRACER TECHNIQUES
Descriptors DEC
AMINES; ANIMALS; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; AZAARENES; AZOLES; BETA DECAY RADIOISOTOPES; BETA-PLUS DECAY RADIOISOTOPES; CARBON ISOTOPES; COMPUTERIZED TOMOGRAPHY; DIAGNOSTIC TECHNIQUES; DRUGS; EMISSION COMPUTED TOMOGRAPHY; EVEN-ODD NUCLEI; HETEROCYCLIC COMPOUNDS; HYDROCARBONS; HYDROXY COMPOUNDS; INDOLES; ISOTOPE APPLICATIONS; ISOTOPES; LIGHT NUCLEI; MAMMALS; MEMBRANE PROTEINS; MINUTES LIVING RADIOISOTOPES; NEUROREGULATORS; NUCLEI; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PROTEINS; PYRROLES; RADIOISOTOPES; RADIOPROTECTIVE SUBSTANCES; RESPONSE MODIFYING FACTORS; RODENTS; SYMPATHOMIMETICS; TOMOGRAPHY; TRYPTAMINES; VERTEBRATES

Optional Information

Notes
20 refs.