[¹⁸F]Nifene test-retest reproducibility in first-in-human imaging of α4β2* nicotinic acetylcholine receptors

Abstract

The aim of this study was to examine the suitability of [18 F]nifene, a novel α4β2* nicotinic acetylcholine receptor (nAChR) radiotracer, for in vivo brain imaging in a first-in-human study. Methods Eight healthy subjects (4 M,4 F;21–69,44 ±21 yrs) underwent a [18F]nifene positron emission tomography scan (200 ±3.7 MBq), and seven underwent a second scan within 58 ±31 days. Regional estimates of DVR were measured using the multilinear reference tissue model (MRTM2) with the corpus callosum as reference region. DVR reproducibility was evaluated with test–retest variability (TRV) and intraclass correlation coefficient (ICC). Results The DVR ranged from 1.3 to 2.5 across brain regions with a TRV of 0–7%, and did not demonstrate a systematic difference between test and retest. The ICCs ranged from 0.2 to 0.9. DVR estimates were stable after 40 min. Conclusion The binding profile and tracer kinetics of [18F]nifene make it a promising α4β2* nAChR radiotracer for scientific research in humans, with reliable DVR test–retest reproducibility.

Human biodistribution and dosimetry of [ 18 F]nifene, an α4β2* nicotinic acetylcholine receptor PET tracer

“…Based on the maximum allowable dose of five rem for the urinary bladder, the maximum injected dose is 278 MBq (7.5 mCi) without bladder voiding, and 519 MBq (14 mCi) when bladder voiding is performed hourly following dose administration. Previous human neuroimaging studies performed by our group [13] indicate that a 185 MBq injection of [ 18 F]nifene is sufficient to obtain accurate binding estimates in the brain, which would result in a WB effective dose of 0.5 rem and a urinary bladder dose of 3.33 rem per scan (1.78 rem with hourly voiding). This would allow for up to four 185 MBq [ 18 F]nifene scans within the period of a year, which is beneficial for studies that might require baseline and subsequent follow-up scans.…”

“…[ 18 F]Nifene is a second-generation α4β2 nAChR radioligand with fast kinetic properties that have been evaluated in preclinical models (mice, rats and rhesus macaques) [6–12]. Recently, [ 18 F]nifene was evaluated in humans for the first time, demonstrating suitable in vivo specific binding in α4β2* nAChR dense regions with rapid kinetics resulting in reliable binding estimates from as little as 40 minutes of dynamic acquisition [13]. Preclinical dosimetry and toxicology performed in mice and extrapolated to humans suggested [ 18 F]nifene doses of up to 850 MBq are within human radiation dose limits [9].…”

Human brain imaging of nicotinic acetylcholine α4β2* receptors using [18F]Nifene: Selectivity, functional activity, toxicity, aging effects, gender effects, and extrathalamic pathways

“…Our tracer design included the pyridinylether backbone which led to the successful development of novel radiotracer [ 18 F]Nifene (Figure b). A major advantage of [ 18 F]Nifene is the significantly shorter scan time to provide quantitative PET data (40 min, Lao et al, ). A shorter scan time is important for several reasons: (1) Patient comfort, especially when the scans are to be carried out on the elderly and ailing population and thus improve subject compliance; (2) Motion artifacts, which often accompany scans and are critical with higher resolution scanners; and (3) Scanner time, due to increased volume of PET studies, scanner time is limited.…”

“…A shorter scan time is important for several reasons: (1) Patient comfort, especially when the scans are to be carried out on the elderly and ailing population and thus improve subject compliance; (2) Motion artifacts, which often accompany scans and are critical with higher resolution scanners; and (3) Scanner time, due to increased volume of PET studies, scanner time is limited. Compared to existing agents (Kuwabara et al, ), [ 18 F]Nifene has shown to be superior in terms of imaging times in all species, providing reasonable target‐to‐nontarget ratios and providing the ability to visualize extrathalamic receptors (Lao et al, ).…”

News and views on in-vivo imaging of neurotransmission using PET and MRI

“…Novel radiotracers for imaging β2* (*denotes the presence of other subunits in the receptor composition, i.e. α4β2, α6α4β2, and α6β2) with faster kinetics and favorable binding parameters that have already been tested in humans include [ 18 F]AZAN 29 , [ 18 F]nifene 30 , (−)-[ 18 F]flubatine 31 and (+)-[ 18 F]Flubatine 32 .…”