The potential of (−)‐o‐[¹¹C]methylvesamicol for diagnosing cholinergic deficit dementia

Synthesis and evaluation of a new vesamicol analog o-[11C]methyl-trans-decalinvesamicol as a PET ligand for the vesicular acetylcholine transporter

“…[ 11 C]OMDV was prepared from o-trimethylstannyl-transdecalinvesamicol (OTDV) (1.9 mg, 4.0 lmol), tris(dibenzylideneacetone)dipalladium(0) (Pd 2 (dba) 3 ) (1.3 mg, 1.4 lmol), copper chloride (Cu(I)Cl) (0.28 mg, 0.27 lmol), cesium fluoride (CsF) (1.1 mg, 7 lmol), and tri(o-tol)phosphine ((o-tol) 3 P) (6.5 mg, 22 lmol) by a palladium-promoted cross-coupling reaction using [ 11 C]methyl iodide [18,24]. [ 11 C]OMDV was isolated using a reverse phase HPLC column (Waters XBridge Prep C18 (5 lm), 10 mm 9 250 mm) with a mobile phase of acetonitrile/50 mMAcONH 4 in 0.1 % AcOH (45/55) at a flow rate of 6.0 mL/min (UV detector at 254 nm).…”

“…Values are the mean ± standard deviation (SD) of four rats (n = 4) Discussion [ 11 C]OMDV was synthesized by a palladium-promoted cross-coupling reaction with [ 11 C]methyl iodide [18,24].…”

“…Therefore, VAChT may be an excellent in vivo target substrate for the diagnosis of AD. Because vesamicol (2-(4-phenylpiperidino)cyclohexanol) was reported to bind to VAChT [10,11], many radiolabeled vesamicol analogs have been investigated as potential VAChT imaging ligands for use in PET or SPECT imaging [12][13][14][15][16][17][18]. However, many of the reported vesamicol analogs were shown to be insufficient for use as VAChT imaging ligands, due to also binding to sigma receptors (r-1 and r-2) [19].…”

Positron emission tomography imaging of (2R,3R)-5-[18F]fluoroethoxybenzovesamicol in rat and monkey brain: a radioligand for the vesicular acetylcholine transporter

“…Successful imaging of the VAChT in the human brain, including losses in disease including Alzheimer’s, has been reported using a SPECT radioiodinated ligand 5-[ 123 I]iodobenzovesamicol ((-)-5-IBVM) [4,5,6,7]. For potential use in PET, radioligands labeled with the positron-emitting radionuclides carbon-11 and fluorine-18 were reported as early as 1990 [8,9] and there has been continued interest in further evaluation of both SPECTand PET radioligands for imaging of the VAChT binding site in the human brain [10,11]. …”

In Vitro and In Vivo Characterization of Two C-11-Labeled PET Tracers for Vesicular Acetylcholine Transporter

“…published a comprehensive review of PET radioligands for imaging VAChT [9]. Although numerous compounds have been developed as potential PET ligands for imaging VAChT, less than ten have been evaluated in NHP or human subjects [25, 29–40]. Very few are still considered potential candidates for clinical studies due to problems including poor selectivity over σ receptors, rapid metabolism, defluorination, low extraction from the blood, and slow brain kinetics that require a long time to reach pseudoequilibrium [7, 9].…”