Linked Life Data

14642577

Source:http://linkedlifedata.com/resource/pubmed/id/14642577

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2003-12-3
pubmed:abstractText
In recent years, there has been considerable effort to design and synthesize radiotracers suitable for use in Positron Emission Tomography (PET) imaging of the alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR) subtype. A new fluoropyridinyl derivative of (-)-cytisine (1), namely (-)-9-(2-fluoropyridinyl)cytisine (3, K(i) values of 24 and 3462 nM for the alpha4beta2 and alpha7 nAChRs subtypes, respectively) has been synthesized in four chemical steps from (-)-cytisine and labelled with fluorine-18 (T(1/2): 119.8 min) using an efficient two-step radiochemical process [(a). nucleophilic heteroaromatic ortho-radiofluorination using the corresponding N-Boc-protected nitro-derivative, (b). TFA removal of the Boc protective group]. Typically, 20-45 mCi (0.74-1.67 GBq) of (-)-9-(2-[18F]fluoropyridinyl)cytisine ([18F]-3, 2-3 Ci/micromol or 74-111 GBq/micromol) were easily obtained in 70-75 min starting from a 100 mCi (3.7 GBq) aliquot of a cyclotron-produced [18F]fluoride production batch (20-45% non decay-corrected yield based on the starting [18F]fluoride). The in vivo pharmacological profile of (-)-9-(2-[18F]fluoropyridinyl)cytisine ([18F]-3) was evaluated in rats with biodistribution studies and brain radioactivity monitoring using intracerebral radiosensitive beta-microprobes. The observed in vivo distribution of the radiotracer in brain was rather uniform, and did not match with the known regional densities of nAChRs. It was also significantly different from that of the parent compound (-)-[3H]cytisine. Moreover, competition studies with (-)-nicotine (5 mg/kg, 5 min before the radiotracer injection) did not reduce brain uptake of the radiotracer. These experiments clearly indicate that (-)-9-(2-[18F]fluoropyridinyl)cytisine ([18F]-3) does not have the required properties for imaging nAChRs using PET.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0968-0896
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5333-43
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Synthesis of a [2-pyridinyl-18F]-labelled fluoro derivative of (-)-cytisine as a candidate radioligand for brain nicotinic alpha4beta2 receptor imaging with PET.
pubmed:affiliation
Département de Recherche Médicale, CEA/DSV, 4 place du Général Leclerc, F-91401 Orsay, France.
pubmed:publicationType
Journal Article