title: Development and characterization of [123I]iodotiagabine for in-vivo GABA-transporter imaging.
abstract: The increased knowledge of molecular changes associated with different neurological disorders calls for the development of novel radioligands. Tiagabine (Gabitril) is an anticonvulsive drug that binds selectively to GABA transporter-1 and thereby inhibits GABA uptake. As radioligands for in-vivo imaging of the GABA transporter are not yet available, we radiolabelled tiagabine and assessed its efficacy for in-vivo imaging of these transporters. Tiagabine was first brominated at its vinylic part, which was then exchanged with I. Next, anaesthetized rats received a bolus injection of [I]iodotiagabine in their tail vein, which was immediately followed by acquisition of planar and high-resolution micro-single-photon emission computed tomography (SPECT) images of the total body with special focus on the brain. Uptake in anatomical regions was assessed by coregistration of micro-SPECT with micro-CT images. Tiagabine labelling with I resulted in 50% yield and 99.7% radiochemical purity. Within 3 h after injection, SPECT demonstrated an increased signal-to-background ratio in the nasal mucosa and/or the Harderian glands but not in the brain. In addition we observed an increased signal-to-background ratio in organs such as the thyroid, heart, liver, kidney and bladder. More than 99% pure I-labelled tiagabine can be obtained and applied in animal micro-SPECT studies. However, this new radioligand is not taken up sufficiently by the brain and therefore cannot be used to successfully detect cerebral GABA transporters.
authors.affiliation: Department of Neurosurgery, School of Mental Health and Neurosciences, Maastricht Institute for Neuromodulation Development (MIND), Maastricht University Medical Center, PO Box 5800,6202 AZ Maastricht, The Netherlands. o.schijns@mumc.nl
authors.forename: Olaf
authors.initials: O
authors.lastname: Schijns
authors.forename: Marinus
authors.initials: M
authors.lastname: van Kroonenburgh
authors.forename: Freek
authors.initials: F
authors.lastname: Beekman
authors.forename: Joost
authors.initials: J
authors.lastname: Verbeek
authors.forename: Jacobus
authors.initials: J
authors.lastname: Herscheid
authors.forename: Kim
authors.initials: K
authors.lastname: Rijkers
authors.forename: Veerle
authors.initials: V
authors.lastname: Visser-Vandewalle
authors.forename: Govert
authors.initials: G
authors.lastname: Hoogland
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism*; D009557:Nipecotic Acids / Q000138:chemical synthesis*; D051381:Rats; D013876:Thiophenes / Q000138:chemical synthesis*; D000078308:Tiagabine; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; D009557:Nipecotic Acids; D013876:Thiophenes; C582327:iodotiagabine; D000078308:Tiagabine