Development and characterization of [123I]iodotiagabine for in-vivo GABA-transporter imaging

Nucl Med Commun. 2013 Feb;34(2):175-9. doi: 10.1097/MNM.0b013e32835bbbd7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemistry Techniques, Synthetic
  • GABA Plasma Membrane Transport Proteins / metabolism*
  • Nipecotic Acids / chemical synthesis*
  • Rats
  • Thiophenes / chemical synthesis*
  • Tiagabine
  • Tomography, Emission-Computed, Single-Photon / methods*


  • GABA Plasma Membrane Transport Proteins
  • Nipecotic Acids
  • Thiophenes
  • iodotiagabine
  • Tiagabine