PMID- 24929961
OWN - NLM
STAT- MEDLINE
DCOM- 20150312
LR  - 20151119
IS  - 1872-9614 (Electronic)
IS  - 0969-8051 (Linking)
VI  - 41
IP  - 8
DP  - 2014 Sep
TI  - Synthesis and preclinical evaluation of carbon-11 labelled 
      N-((5-(4-fluoro-2-[(11)C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine as a 
      PET tracer for NR2B subunit-containing NMDA receptors.
PG  - 670-80
LID - S0969-8051(14)00262-5 [pii]
LID - 10.1016/j.nucmedbio.2014.04.131 [doi]
AB  - INTRODUCTION: The N-methyl-D-Aspartate (NMDA) receptor plays an important role in 
      learning and memory. Overactivation is thought to play an important role in 
      neurodegenerative disorders such as Alzheimer's disease. Currently, it is not 
      possible to assess N-methyl-D-aspartate receptor (NMDAr) bio-availability in 
      vivo. The purpose of this study was to develop a positron emission tomography 
      (PET) ligand for the NR2B binding site of the NMDA receptor. METHODS: 
      N-((5-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine was 
      radiolabelled with carbon-11 in the phenyl moiety. Biodistribution and blocking 
      studies were carried out in anaesthetized mice and in non-anaesthetized rats. 
      RESULTS: 
      N-((5-(4-fluoro-2-[(11)C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine was 
      prepared in 49+/-3% (decay-corrected) yield, affording 4.1+/-0.3 GBq of formulated 
      product at the end of synthesis with a radiochemical purity of >99% and with a 
      specific activity of 78+/-10 GBq/mumol. CONCLUSION: A new NR2B PET ligand was 
      developed in high yield. [(11)C]4 readily enters the brain and binds to the NR2B 
      subunit-containing NMDAr in the rodent brain. High sigma-1 receptor binding may, 
      however, limit its future application as a PET probe for imaging the NR2B 
      subunit-containing NMDAr. Anaesthesia has an effect on NMDAr function and 
      therefore can complicate interpretation of preclinical in vivo results. In 
      addition, effects of endogenous compounds cannot be excluded. Despite these 
      potential limitations, further studies are warranted to investigate the values of 
      [(11)C]4 as an NR2B PET ligand.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Christiaans, Johannes A M
AU  - Christiaans JA
AD  - Department of Radiology & Nuclear Medicine, VU University Medical Center, 
      Amsterdam, the Netherlands.
FAU - Klein, Pieter J
AU  - Klein PJ
AD  - Department of Radiology & Nuclear Medicine, VU University Medical Center, 
      Amsterdam, the Netherlands.
FAU - Metaxas, Athanasios
AU  - Metaxas A
AD  - Department of Radiology & Nuclear Medicine, VU University Medical Center, 
      Amsterdam, the Netherlands.
FAU - Kooijman, Esther J M
AU  - Kooijman EJ
AD  - Department of Radiology & Nuclear Medicine, VU University Medical Center, 
      Amsterdam, the Netherlands.
FAU - Schuit, Robert C
AU  - Schuit RC
AD  - Department of Radiology & Nuclear Medicine, VU University Medical Center, 
      Amsterdam, the Netherlands.
FAU - Leysen, Josee E
AU  - Leysen JE
AD  - Department of Radiology & Nuclear Medicine, VU University Medical Center, 
      Amsterdam, the Netherlands.
FAU - Lammertsma, Adriaan A
AU  - Lammertsma AA
AD  - Department of Radiology & Nuclear Medicine, VU University Medical Center, 
      Amsterdam, the Netherlands.
FAU - van Berckel, Bart N M
AU  - van Berckel BN
AD  - Department of Radiology & Nuclear Medicine, VU University Medical Center, 
      Amsterdam, the Netherlands.
FAU - Windhorst, Albert D
AU  - Windhorst AD
AD  - Department of Radiology & Nuclear Medicine, VU University Medical Center, 
      Amsterdam, the Netherlands. Electronic address: ad.windhorst@vumc.nl.
LA  - eng
PT  - Journal Article
DEP - 20140510
PL  - United States
TA  - Nucl Med Biol
JT  - Nuclear medicine and biology
JID - 9304420
RN  - 0 (Carbon Radioisotopes)
RN  - 0 (Cyclopentanes)
RN  - 0 (Ligands)
RN  - 0 (N-((5-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Phenols)
RN  - 0 (Piperidines)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Ro 25-6981)
SB  - IM
MH  - Animals
MH  - Biological Transport/drug effects
MH  - Carbon Radioisotopes
MH  - Chemistry Techniques, Synthetic
MH  - Cyclopentanes/*chemical synthesis/metabolism/pharmacokinetics
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Ligands
MH  - Male
MH  - Mice
MH  - Phenols/pharmacology
MH  - Piperidines/pharmacology
MH  - Positron-Emission Tomography/*methods
MH  - Pyridines/*chemical synthesis/metabolism/pharmacokinetics
MH  - Radiochemistry
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Tissue Distribution/drug effects
OTO - NOTNLM
OT  - Carbon-11
OT  - NR2B
OT  - PET
EDAT- 2014/06/16 06:00
MHDA- 2015/03/13 06:00
CRDT- 2014/06/16 06:00
PHST- 2014/01/08 00:00 [received]
PHST- 2014/04/11 00:00 [revised]
PHST- 2014/04/26 00:00 [accepted]
PHST- 2014/06/16 06:00 [entrez]
PHST- 2014/06/16 06:00 [pubmed]
PHST- 2015/03/13 06:00 [medline]
AID - S0969-8051(14)00262-5 [pii]
AID - 10.1016/j.nucmedbio.2014.04.131 [doi]
PST - ppublish
SO  - Nucl Med Biol. 2014 Sep;41(8):670-80. doi: 10.1016/j.nucmedbio.2014.04.131. Epub 
      2014 May 10.