Radiosynthesis of [11C]SNAP-7941—the first PET-tracer for the melanin concentrating hormone receptor 1 (MCHR1)

Abstract

The melanin concentrating hormone (MCH) system is a new target to treat human disorders. Our aim was the preparation of the first PET-tracer for the MCHR1. [11C]SNAP-7941 is a carbon-11 labeled analog of the published MCHR1 antagonist SNAP-7941. The optimum reaction conditions were 2 min reaction time, ≤25 °C reaction temperature, and 2 mg/mL precursor (SNAP-acid) in acetonitrile, using [11C]CH3OTf as methylation agent. [11C]SNAP-7941 was prepared in a reliable and feasible manner with high radiochemical yields (2.9±1.6 GBq; 11.5±6.4% EOB, n=15).

Syntheses of Precursors and Reference Compounds of the Melanin-Concentrating Hormone Receptor 1 (MCHR1) Tracers [11C]SNAP-7941 and [18F]FE@SNAP for Positron Emission Tomography

“…The selective high-affinity MCHR1 antagonist SNAP-7941 1 was used as a promising basis for the development of the PET tracers [ [1,[15][16][17]. This paper focuses on the synthesis of the non-radioactive precursors and reference compounds of [ The synthesis of these polyfunctional SNAP derivatives comprised many commonly used syntheses, including numerous methods attempting to cleave the methyl ester of 1 to prepare SNAP-acid 2, which unfortunately were unsuccessful.…”

“…A mixture of 5-(2-methoxyacetyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (7, 38.74 g, 179.20 mmol) and allyl alcohol (57.4 mL, 537.60 mmol) in toluene (10.0 mL) was heated to 80 °C for 24 h. After cooling to room temperature the solvent was removed in vacuo and the residue was purified by bulb-to-bulb distillation to give 20.04 g (51.7%) of 13 as a yellow oil. (15). To a well-stirred solution of 4-methoxybenzyl 4-methoxy-3-oxobutanoate (8, 330 mg, 1.31 mmol), 3,4-difluorobenzaldehyde (192 mg, 1.35 mmol) and urea (118 mg, 1.96 mmol) in THF (1.2 mL), Cu 2 O (19 mg, 0.13 mmol), glacial acetic acid (7.6 µL) and boron trifluoride diethyl etherate (0.2 mL, 240 mg, 1.69 mmol) were added.…”

“…The syntheses leading to 2 and the allyl protected derivatives 11, 18, 25, and 32 were performed as already described by Philippe et al [15], as were those of compounds 3 and 4 [16]. The syntheses of the already known compounds 1, 14, 21 and 28 were carried out according to Schönberger [17].…”

“…Synthesis of compounds 2, 7, 11, 18, 25 and 32 was conducted according to Philippe et al [15]. Synthesis of compounds 3 and 4 was conducted according to Philippe et al [16].…”

“…PET is an important tool both in medical diagnostics and clinical research of molecular processes due to its non-invasive nature as an imaging technique. Based on the already established selective, high-affinity MCHR1 antagonist SNAP-7941 (1), which has anorectic, antidepressant, and anxiolytic effects [10][11][12][13][14], the present study aimed at the synthesis and evaluation of precursors and reference standards of the novel MCH receptor 1 PET tracers [ In particular, this paper focuses on the synthesis of the novel MCHR1 PET tracers' 1a and 4a, non-radioactive reference compound FE@SNAP 4 as well as the precursors SNAP-acid 2 and TOE@SNAP 3, which represents the preliminary non-radioactive work paving the way for the subsequent radiosyntheses [15,16].…”