In vitro, the novel diazabicyclononane NS 4194 has several thousandfold selectivity for blocking the transport into rat brain synaptosomes of [ 3 H]-serotonin in comparison to [3H]-dopamine or [ 3 H]-noradrenaline. We have prepared [ 1 1 C]-NS 4194 in order to test its properties for PET imaging of brain serotonin transporters in comparison with the well-documented tracer [ 1 1 C]-DASB. Both compounds had rapid clearance from blood to brain of living pigs. The apparent equilibrium distribution volumes in cerebellum were 35 ml g - 1 for [ 1 1 C]-NS 4194 and 11 ml g - 1 for [ 1 1 C]-DASB. Pretreatment of pigs with citalopram did not reduce the uptake of either tracer in cerebellum, validating the use of that tissue as a nonbinding reference tissue for kinetic analysis of specific binding. The binding potential (pB) calculated for [ 1 1 C]-NS 4194 using arterial input models was close to 0.5 in the telencephalon, and was 60% displaced by citalopram. However, the reference tissue method of Lammertsma was unsuited to calculate pB for this tracer, apparently due to its excessive nonspecific binding. In contrast to the relatively homogeneous binding of [ 1 1 C]-NS 4194, the pB of [ 1 1 C]-DASB ranged from 0.6 in frontal cortex to 2 in the mesencephalon when calculated by the method of Lammertsma. Parametric maps of the pB of [ 1 1 C]-DASB showed a pattern consistent with the known distribution of serotonin transporters in pig brain in vitro, and there was a uniform displacement of 80% of the specific binding after citalopram treatment in vivo. In conclusion, [ 1 1 C]-DASB is in several respects superior to [ 1 1 C]-NS 4194 for the detection of serotonin uptake sites by PET.

[11C]-NS 4194 versus [11C]-DASB for PET imaging of serotonin transporters in living porcine brain.

[11C]Mirtazapine for PET neuroimaging: radiosynthesis and initial evaluation in the living porcine brain

Stereoselective neuroimaging in vivo.

PET evaluation of the uptake of N-[11C]methyl CP-643,051, an NK1 receptor antagonist, in the living porcine brain.

Current interest in studying molecular processes as they occur in the living brain has accelerated the use of laboratory animals for neuroimaging of novel radiolabelled compounds. In particular, positron emission tomography (PET) has contributed to the development of radiolabelled compounds for assessing molecular processes in the living brain. The dynamics of PET typically require a relatively large organ size and blood supply in order to properly evaluate radioligand binding kinetics. To fulfil these requirements, pigs have often been used in such studies. Today, much is known about the metabolism, neurotransmission and molecular binding properties of the living porcine brain, and most findings support similarities between neuronal mechanisms in pigs and humans. Here, we review 10-years of PET findings on neuromolecular processes in the living porcine brain and, whenever possible, we relate PET findings in pigs to those obtained in humans.

http://sjlas.org/index.php/SJLAS/article/download/246/223

PET Neuroimaging in Pigs

Synthesis and evaluation of racemic [11C]NS2456 and its enantiomers as selective serotonin reuptake radiotracers for PET

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Synthesis and evaluation of racemic [11C]NS2456 and its enantiomers as selective serotonin reuptake radiotracers for PET