Positron emission tomography imaging of the serotonin transporter in the pig brain using [¹¹C](+)‐McN5652 and S‐([¹⁸F]fluoromethyl)‐(+)‐McN5652

Abstract

S-([(18)F]fluoromethyl)-(+)-McN5652 ([(18)F](+)-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 [(11)C](+)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 [(11)C](+)McN5652 or [(18)F](+)-FMe-McN5652 in the time period between 75 and 115 min after radiotracer injection. The specific binding of the (18)F-labeled derivative was about 40% higher than that of the (11)C-labeled derivative. A strong inhibition of the specific binding was observed for both radiotracers after pretreatment with the selective 5-HT uptake inhibitor citalopram. [(18)F](+)-FMe-McN5652 showed faster kinetics than [(11)C](+)McN5652. It reached the binding equilibrium during a study length of 120 min, which was not the case for [(11)C](+)McN5652. It is concluded that [(18)F](+)-FMe-McN5652 is suitable for 5-HT transporter imaging with PET.

Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

“…18, where C a refers to the arterial plasma and BP estimated from these curves [209,260] . This clearly demonstrated the specifi city of the radiotracer uptake.…”

“…Linear systems of ordinary differential equations describe the changes of radiotracer contents in these models. Based on these equations, the rate constants for the blood-brain and brain-blood transfer (K 1 and k 2 ' or k 2 "), and the rate constants for the specifi c binding/release and BP estimated from these curves [209,260] . This clearly demonstrated the specifi city of the radiotracer uptake.…”

Effect of Moderate Hypercapnic Hypoxia on Cerebral Dopaminergic Activity and Brain O2 Uptake in Intrauterine Growth–Restricted Newborn Piglets

“…For attenuation and scatter correction, a transmission scan using three rotating 68 Ge rod sources was performed before the emission scan. Radioactivity data of selected volumes of interest were obtained using a standardized procedure that was recently described in detail (28). Briefly, volumes of interest defined on magnetic resonance images were aligned to the added PET radioactivity images interactively using an "in house" data analysis tool.…”

Imaging of the brain serotonin transporters (SERT) with 18F-labelled fluoromethyl-McN5652 and PET in humans

“…Its use, however, is limited by the short half-life of 11 C (20 min), the moderate cortical test-retest reliability [10], and the lack of quantifying endogenous serotonin [11]. Labelling with 18 F might help at least in part to overcome these drawbacks because such tracers would allow later data acquisition times (due to the longer physical half-life of 18 F, 108 min), which is useful for the investigation of the tracer kinetics in brain tissue (modelling). Furthermore, 18 F-labelled radiotracers provide the opportunity for widespread application within a satellite concept.…”

“…Labelling with 18 F might help at least in part to overcome these drawbacks because such tracers would allow later data acquisition times (due to the longer physical half-life of 18 F, 108 min), which is useful for the investigation of the tracer kinetics in brain tissue (modelling). Furthermore, 18 F-labelled radiotracers provide the opportunity for widespread application within a satellite concept. Although the results of preclinical studies using novel 18 F-labelled compounds for SERT imaging have been published [12], human data are not available and the evaluation of in vivo properties of such radiotracers is still ongoing [12][13][14] We developed a [ 18 F]fluoromethyl analogue of (+)-McN5652 [15] which shows favourable preclinical properties for imaging SERT.…”