Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Berndt, U; Stanetty, C; Wanek, T; Kuntner, C; Stanek, J; Berger, M; Bauer, M; Henriksen, G; Wester, HJ; Kvaternik, H; Angelberger, P; Noe, C.
Synthesis of a [(18)F]fluorobenzothiazole as potential amyloid imaging agent
J LABELLED COMPD RAD. 2008; 51(3-4): 137-145.
Doi: 10.1002/jlcr.1476
Web of Science
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- Co-Autor*innen der Med Uni Graz
- Kvaternik Herbert
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- Abstract:
- This study describes the synthesis of a fluoroethylated derivative of [N-methyl-(11)C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole ([(11)C]6-OH-BTA-1; Pittsburgh Compound B (PIB)), an already established amyloid imaging agent. The [(11)C]methylamino group of [(11)C]6-OH-BTA-1 was formally replaced by a fluoroethyl group in a cold synthesis via N-alkylation of N-Boc-2-(4'-aminophenyl)-6-(methoxyethoxymethoxy)benzothiazole with fluoroethyl tosylate. Subsequent deprotection gave the target compound 2-[4'-(2-fluoroethyl)aminophenyl]-6-hydroxybenzothiazole (FBTA). In a radioligand competition assay on aggregated synthetic amyloid fibrils using N-[(3)H-methyl]6-OH-BTA-1, 100 nM FBTA inhibited binding with 93 +/- 1 and 83 +/- 11% efficiency for A beta(1-40) and A beta(1-42), respectively. For the radiosynthesis a precursor carrying a tosylethyl moiety was prepared allowing the introduction of [(18)F]fluoride via nucleophilic substitution with [(18)F]tetra-n-butyl-ammonium fluoride (TBAF). Subsequent removal of all protecting groups was performed in a one-pot procedure followed by semi-preparative HPLC, delivering the target compound [(18)F]FBTA in good radiochemical yield of 21% on average and radiochemical purity of >= 98% at EOS. In vitro autoradiography on human postmortem AD brain tissue slices showed intense cortical binding of [(18)F]FBTA (11 nM), which was displaced in presence of 6-OH-BTA-1 (1 mu M). Brain up-take was evaluated in wild-type (wt) mice with microPET imaging. Based on these results, [(18)F]FBTA appears to be a suitable candidate tracer for amyloid imaging in humans.
- Find related publications in this database (Keywords)
- Alzheimer's disease
- PET
- [(18)F] FBTA
- amyloid
- [(11)C] BTA