Positron Emission Tomography Imaging of the Serotonin Transporter in the Pig Brain Using [¹¹C](+)-McN5652 and S-([¹⁸F]fluoromethyl)-(+)-McN5652

Positron Emission Tomography Imaging of the Serotonin Transporter in the Pig Brain Using [¹¹C](+)-McN5652 and S-([¹⁸F]fluoromethyl)-(+)-McN5652

Brust, P.; Zessin, J.; Kuwabara, H.; Pawelke, B.; Kretzschmar, M.; Hinz, R.; Bergman, J.; Eskola, O.; Solin, O.; Steinbach, J.; Johannsen, B.

S-(¹⁸F]fluoromethyl)-(+)-McN5652 ([¹⁸F](+)-FMe-McN5652) has recently been synthesized as a new potential radiotracer for positron emission tomography (PET) imaging of the 5-HT transporter. It is an analog of [¹¹C](+)-McN5652, which has been used in clinical PET studies for 5-HT transporter imaging. This article describes the comparison of these two radiotracers in pigs with respect to their in vivo binding characteristics. PET images revealed that the highest accumulation of both radiotracers was found in the ventral midbrain, thalamus, olfactory lobe, and pons which is consistent with the known density of 5-HT transporters. The specific binding was determined by subtracting the values of the inactive (-) enantiomers or of the occipital cortex from those obtained with [¹¹C](+)-McN5652 or [¹⁸F](+)-FMe-McN5652 in the time period between 75 and 115 min after radiotracer injection. The specific binding of the ¹⁸F-labeled derivative was about 40 % higher than that of the ¹¹C-labeled derivative. A strong inhibition of the specific binding was observed for both radiotracers after pre-treatment with the selective 5-HT uptake inhibitor citalopram. [¹⁸F](+)-FMe-McN5652 showed faster kinetics than [¹¹C](+)-McN5652. It reached the binding equilibrium during a study length of 120 min, which was not the case for [¹¹C](+)-McN5652. It is concluded that [¹⁸F-FMe-McN5652 is suitable for 5-HT transporter imaging with PET.

Keywords: serotonin transporter; receptor imaging; positron emission tomography; porcine brain; [¹⁸F](+)-FMe-McN5652; citalopram

Synapse (2003) 47: 143-151

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