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Unexpected decrease in in vivo binding of [3H]QNB in the mouse cerebral cortex in the developing brain - A comparison

Osamu Inoue1, Toshiyuki Sato1, Kaoru Kobayashi1

  • 1Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan.

Nuclear Medicine and Biology
|November 1, 2018
PubMed
Summary
This summary is machine-generated.

Discrepancies in muscarinic receptor ligand binding were studied using radiolabeled Quinuclidinyl Benzilate (QNB) and N-[11C]methylpiperidyl Benzilate ([11C]NMPB) in mice. Results suggest microenvironmental factors create a

Keywords:
BrainDevelopmentDiffusion boundaryMouse[(11)C]NMPB[(3)H]QNB

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Radiochemistry

Background:

  • Significant discrepancies exist between in vitro and in vivo muscarinic receptor ligand binding.
  • In vivo cerebellar binding of 3H-labeled Quinuclidinyl Benzilate (QNB) is observed despite low binding site density.
  • Understanding in vivo binding phenomena requires comparative studies of different radioligands.

Purpose of the Study:

  • To compare the in vivo and in vitro binding of two muscarinic receptor ligands, [3H]QNB and N-[11C]methylpiperidyl Benzilate ([11C]NMPB).
  • To investigate the influence of brain development on muscarinic receptor ligand binding in mice.
  • To elucidate the role of microenvironmental factors in receptor binding.

Main Methods:

  • In vitro binding parameters of [3H]QNB were determined using brain homogenates.
  • Time course of radioactivity concentration (TACs) was measured in mouse cerebral cortex and cerebellum after injecting [3H]QNB and [11C]NMPB.
  • Dual tracer administration with and without carrier QNB was used, followed by graphical analysis for quantitative in vivo binding.

Main Results:

  • In vitro, muscarinic receptor binding sites in the cerebral cortex increased by 17% during development.
  • In vivo, [3H]QNB binding decreased in the cerebral cortex, while [11C]NMPB binding increased.
  • In vivo saturation analysis of [3H]QNB in young mice indicated apparent positive cooperativity.

Conclusions:

  • Microenvironmental factors near muscarinic receptors decrease cortical [3H]QNB concentration, forming a 'ligand barrier'.
  • This 'ligand barrier' is modulated during brain development.
  • Combined use of radiolabeled QNB and NMPB can reveal microenvironmental effects on receptor function in vivo.