title: Synthesis of [3',5'-3H2]-alpha-fluoromethyl-tyrosine as a radioactive specific label of rat brain tyrosine hydroxylase.
abstract: The [3',5']-ditritio-alpha-fluoromethyl-tyrosine 4 (specific activity 15.0 Ci/mmol) has been synthesized and used as a radioactive probe for rat neuronal tyrosine hydroxylase (TH). The route of synthesis for the preparation of 3 and 4 allowed us to not only introduce a fluorine atom into 3/4 using an inorganic source of fluorine (CsF), but also to take advantage of the high-yielding cyclization of (alpha,beta)-acetamido alcohols mediated by diethylaminosulfur trifluoride (DAST) to give the corresponding oxazolines. The distribution and metabolism of 4 have been studied in control conditions within the rat locus caeruleus (LC). Intracisternal injection of 20 microCi of 4 was followed by a rapid disappearance of 4 (t1/2 = 1.5 h) and by a specific accumulation of radioactivity into the LC anatomical limits. This was investigated each 140 microns along the caudo-rostral axis of the noradrenergic nucleus. In each anatomical interval, its distribution correlated nicely with already described caudo-rostral distribution of TH in noradrenergic cells. Thus, 4 may provide a reliable measure of TH activity in such catecholamine structures.
authors.affiliation: CEA, CE-Saclay, Service des Molécules Marquées, Gif-Sur-Yvette, France.
authors.forename: P
authors.initials: P
authors.lastname: Lafargue
authors.forename: A
authors.initials: A
authors.lastname: Dodi
authors.forename: M
authors.initials: M
authors.lastname: Ponchant
authors.forename: C
authors.initials: C
authors.lastname: Garcia
authors.forename: M
authors.initials: M
authors.lastname: Le Cavorsin
authors.forename: J F
authors.initials: JF
authors.lastname: Pujol
authors.forename: J P
authors.initials: JP
authors.lastname: Lellouche
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000201:enzymology*; D008781:Methyltyrosines; D015335:Molecular Probes; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014316:Tritium; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D008781:Methyltyrosines; D015335:Molecular Probes; D014316:Tritium; D014443:Tyrosine; C040511:alpha-monofluoromethyl-4-tyrosine; D014446:Tyrosine 3-Monooxygenase