%0 Journal Article
%A Kreft, Sabrina
%A Bier, Dirk
%A Holschbach, Marcus
%A Schulze, Annette
%A Coenen, Heinrich Hubert
%T New potent A1 adenosine receptor radioligands for positron emission tomography
%J Nuclear medicine and biology
%V 44
%@ 0969-8051
%C Amsterdam [u.a.]
%I Elsevier Science
%M FZJ-2016-07111
%P 69 - 77
%D 2017
%X 8-Cyclopentyl-3-(3-[18F]fluoropropyl)-1-propylxanthine ([18F]CPFPX) is meanwhile an accepted receptor ligand to examine the A1 adenosine receptor (A1AR) in humans by positron emission tomography (PET). A major drawback of this compound is its rather fast metabolic degradation in vivo.Therefore two new xanthine derivatives, namely 8-cyclobutyl-1-cyclopropymethyl-3-(3-fluoropropyl)xanthine (CBCPM; 5) and 1-cyclopropylmethyl-3-(3-fluoropropyl)-8-(1-methylcyclobutyl)xanthine (CPMMCB; 6) were designed and synthesized as potential alternatives to CPFPX. In membrane binding studies both compounds showed nanomolar affinity for the A1AR. In vitro autoradiographic studies of [18F]5 and [18F]6, using rat brain slices, showed the expected accumulation in regions known to have a high adenosine A1 receptor expression while exhibiting the necessary low unspecific binding. However, in vitro metabolite studies using human liver microsomes revealed a comparable metabolic degradation rate for both new xanthine derivatives and CPFPX.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000390836100006
%R 10.1016/j.nucmedbio.2016.09.004
%U https://juser.fz-juelich.de/record/824539