[18F]FE@SNAP—A new PET tracer for the melanin concentrating hormone receptor 1 (MCHR1): Microfluidic and vessel-based approaches

Abstract

Graphical abstractSNAP-7941 derivatives 1–4 (1: SNAP-7941; 2: [18F]FE@SNAP; 3: SNAP-acid; 4: Tos@SNAP).

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 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].…”

“…Hence, another approach to 4 and 6 had to be established leading to the Steglich esterification [16,38,39] of SNAP-acid 2 (Scheme 14) which is therefore employed as a precursor for the reference compound FE@SNAP 4, for the PET tracer [ Acid 2 was reacted with dicyclohexylcarbodiimide, 4-dimethylaminopyridine, and fluoroethanol or fluoropropanol, respectively, giving the fluoroethylated reference compound 4 in trace yields of 4% but again did not afford 6 in acceptable quantity, although the conversion was confirmed via mass spectrometry. Fluoropropyl ester 6 could not be isolated by different chromatographic purification methods.…”

“…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]. …”

“…The crude product was reacted without further purification in the next step. (16). To a well-stirred solution of 2-(trimethylsilyl)ethyl 4-methoxy-3-oxobutanoate (9, 2.35 g, 10.11 mmol), 3,4-difluorobenzaldehyde (1.48 mg, 10.41 mmol) and urea (910 mg, 15.17 mmol) in THF (8.7 mL), Cu 2 O (146 mg, 1.02 mmol), glacial acetic acid (59 µL) and boron trifluoride diethyl etherate (1.6 mL, 1.82 g, 12.80 mmol) were added.…”

“…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].…”