Synthesis of fluorine-18 labelled adenosine-receptor ligands

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dc.contributor.advisorTrón, Lajos
dc.contributor.authorLehel, Szabolcs
dc.contributor.departmentDE -- Orvos- és Egészségtudományi Centrum -- Általános Orvostudományi Kar -- PET Centrumhu
dc.contributor.departmentElméleti orvostudományok doktori iskolahu
dc.date.accessioned2007-05-15T17:15:11Z
dc.date.available2007-05-15T17:15:11Z
dc.date.issued2002
dc.description.abstractThis thesis presents a study of introduction of fluorine-18, a positron-emitting radioisotope to the designed position of molecules of adenosine type. This thesis also includes strategies of synthesising of precursors, into which the fluorine-18 isotope, either in fluoride ion form or as a suitable fluorine-containing small molecule, can be introduced. The synthesized labelled molecules make the investigation of adenosine-receptors by PET technique possible. Preliminary biological evaluation of one of these molecules, namely 5’-N-(2-[18F]fluoroethyl)-carboxamidoadenosine is also presented. Two molecules were chosen to synthesise their fluorine-18 labelled forms: 5’-deoxy-5’-fluoro-adenosine and 5’-N-(2-fluoroethyl)-carboxamidoadenosine. Both compounds were labelled in two ways, each synthetic route includes nucleophilic fluorination with [18F]fluoride ion. 5’-Deoxy-5’-[18F]fluoro-adenosine would serve as a suitable model-compound for the synthesis of fluorine-18 labelled ligands; the appropriate modification of the adenine moiety leads to increased selectivity towards the chosen receptor subtype. As the radiochemical yields proved to be rather low, using either 5’-deoxy-5’-haloadenosines or N6-benzoyl 2’,3’-isopropylideneadenosine-5’-sulfonates as precursors, we had to resign to label adenosine at that (5’) position. Although N6-benzoyl 2’,3’-isopropylideneadenosine-5’-tosylate, one of these sulfonates was not proven to be a suitable precursor in the radiofluorination reactions, it served as an appropriate starting material in radioiodination reactions. 5’-N-(2-fluoroethyl)-carboxamidoadenosine ([18F]FNECA), as a fluorine-18 labelled analogue of NECA represents a PET isotope labelled agonist with given adenosine receptor specificity. It was synthesised in the following ways: in the reaction of [18F]fluoride with 5’-N,N-ethylene-2’,3’-O-isopropylidenecarboxamido-adenosine as well as by reacting 2-[18F]fluoroethylamine with 2’,3’-O-isopropylideneadenosine-5’-uronic acid. This latter route provides sufficient [18F]FNECA for the subsequent preliminary biological evaluation using PET-technique. According to the preliminary biological evaluation, agonist [18F]FNECA labelled with positron emitting isotope is capable of mapping the distribution for adenosine-receptors of P1 type, as well as investigating of receptor-regulation processes in vivo.en
dc.description.degreePh.D. Thesis ; Positron Emission Tomograph Centre, University of Debrecen, Medical and Health Science Center, 2002hu
dc.description.degreePhDhu_HU
dc.format.extent54, [25] pen
dc.format.extent503705 bytes
dc.format.extent349056 bytes
dc.format.extent690938 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypeapplication/pdf
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dc.identifier.urihttp://hdl.handle.net/2437/2283
dc.languageenghu
dc.language.isohuen
dc.language.isoenen
dc.rightsA kéziratos PhD munkák csak a szerzői jogok maradéktalan tiszteletben tartásával használhatókhu
dc.titleSynthesis of fluorine-18 labelled adenosine-receptor ligandsen
dc.title.subtitlePh.D. Thesisen
dc.title.translatedFluor-18 jelzett adenozin-receptor ligandok szintéziseen
dc.typePhD, doktori értekezéshu
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