Synthesis and evaluation of 3-123I-iodo-5-[2-(S)-3-pyrrolinylmethoxy]-pyridine (niodene) as a potential nicotinic α4β2 receptor imaging agent

Abstract

Nicotinic acetylcholine receptors (nAChRs) are downregulated in disease conditions such as Alzheimer’s and substance abuse. Presently, 123I-5-IA-85380 is used in human studies and requires over 6 hrs of scanning time, thus increases patient discomfort. We have designed and synthesized 3-iodo-5-[2-(S)-3-pyrrolinylmethoxy]pyridine (Niodene) with the aim to have faster binding kinetics compared to 123I-5-IA-85380, which may reduce scanning time and help in imaging studies. Binding affinity Ki of niodene for rat brain α4β2 receptors in brain homogenate assays using 3H-cytisine was 0.27 nM. Niodene, 10 nM displaced >95% of 18F-nifene bound to α4β2 receptors in rat brain slices. By using the iododestannylation method, 123I-niodene was obtained in high radiochemical purity (>95%) but with low radiochemical yield (<5%) and low specific activity (~100 Ci/mmol). Autoradiograms show 123I-niodene localized in the thalamus and cortex, which was displaced by nicotine (thalamus to cerebellum ratio = 4; cortex to cerebellum ratio = 1.6). Methods of radioiodination need to be further evaluated in order to obtain 123I-niodene in higher radiochemical yields and higher specific activity of this potentially useful new SPECT imaging agent.

Spectroscopic, computational modeling and cytotoxicity of a series of meso-phenyl and meso-thienyl-BODIPYs

“…Radioactive isotopically labeled iodine has been effectively used in single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging studies. 16,17 In previous work, 123 I nuclei have been successfully used in nuclear medicine including blood flow, myocardial, and thyroid scintigraphy and for uptake measurements in tumors. 18 The use of radioactively labeled iodine has gained popularity in bioimaging for its longer half-life (ca.…”

Synthesis and Evaluation of Compound Targeting α7 and β2 Subunits in Nicotinic Acetylcholinergic Receptor

“…Due to the clinical importance of nAChRs, evaluating the activity of these receptors can potentially assist in understanding human illness [8][9][10][11]. We have developed several positron emission tomography (PET) imaging agents for non-invasive imaging of highaffinity sites on α4β2* receptors using [ 18 F]nifene [12][13][14][15] (Figure 1), [ 18 F]nifrolene [16], and [ 18 F]nifzetidine [17]; for single-photon emission computed tomography (SPECT), [ 123 I]niodene was prepared [18]; and for PET/SPECT, Niofene [19] was examined. For α7 nAChRs, fewer in vivo PET imaging agents are available, with [ 18 F]ASEM being the promi-Molecules 2023, 28, 8128 2 of 13 nent one [20,21] (Figure 1).…”

Synthesis and Pharmacological Evaluation of α4β2 Nicotinic Ligands with a 3‐Fluoropyrrolidine Nucleus

“…Unfortunately, 5‐[ 123 I]A‐85380 is characterized by slow imaging kinetics with scan times exceeding several hours, which causes patient discomfort 10. It has been reported that decreasing the basicity of the secondary amine is an efficient strategy to obtain ligands with faster brain imaging kinetics, as is the case for [ 123 I]niodene,11 in which a five‐membered 2,5‐dihydro‐1 H ‐pyrrole ring was introduced in place of the azetidine ring of the model compound 5‐[ 123 I]A‐85380 (Figure 1). Inspired by this work, we designed new niodene analogues characterized by a basic pyrrolidine nucleus.…”