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. Author manuscript; available in PMC: 2010 Apr 1.
Published in final edited form as: Synapse. 2009 Apr;63(4):339–358. doi: 10.1002/syn.20611

TABLE I.

Characteristics of nuclear neuroimaging of high-affinity α4β2* neuronal nicotinic acetylcholine receptors (nAChRs)

Study Species of
subjects		 Sample size Radiotracer Duration in
minutes of
scan after
start of
radiotracer
administration		 Form
of
radiotracer
administration		 Method of
plasma
sampling for
modeling		 Method of
modeling		 Conclusion
Current (presented in abstract by Brasic et al., 2001; Musachio et al., 2001; Wong et al., 2001, 2002a) Humans (Homo sapiens) 6 smokers, 6 nonsmokers including 2 nonsmokers with secondhand smoke exposure 5-[123I]IA 300 7 B 5 B + CI Column-switch HPLC (Hilton et al., 2000) DV estimation by kinetic analysis (Zhou et al., 2001)

  • 5-[123I]IA is safe, efficacious in humans (smokers, nonsmokers, people with secondhand smoke exposure
Baldwin et al., 2006 Baboons (Papio anubis) 1 without nicotine exposure 5-[123I]IA 90 1 B HPLC DV estimation by kinetic analysis

  • Uptake high in thalamus, moderate in cortex and basal ganglia, low in cerebellum.

    SPECT brain radioactivity represents5-[123I]IA distribution
Bottlaender et al., 2003 Humans (Homo sapiens) 3 nonsmokers 2-[18F]FA 120 3 B Radioactivity measurements corrected for physical decay Regions of interest on PET scans

  • 2-[18F]FA is safe and efficacious for brain imaging in humans.
Brody et al., 2006 Humans (Homo sapiens) 11 smokers with tobacco dependence 2-[18F]FA 500 11 B + CI before and after cigarette smoking Gas chromatography with nitrogen-phosphorus detection (Jacob et al., 1981) Maximal fractional displacement of radioactivity α4 β2* nAChRs are occupied almost fully in cigarette smokers with tobacco dependence.
Brust et al., 2008 Pigs (mixed German landrace and Pietrain) 24 (−)-[18F]NCFHEB, (+)- [18F]NCFHEB, 2- [18F]FA 420 24 CI HPLC Kinetic analysis with BioMedical Image Quantification Software PMOD Version 2.75 (PMOD Technologies, Zurich, Switzerland)

  • (−)-[18F]NCFHEB attains equilibrium before 2-[18F]FA
Chefer et al., 1998 Rhesus monkeys (Macaca mulatta) 1 5-[123I]IA 270 B HPLC Kinetic analysis with cerebellum as the reference tissue 5-[123 I]IA is safe and efficacious for brain imaging in monkeys.
Chefer et al., 1999 Rhesus monkeys (Macaca mulatta) 2 2-[18F]FA 240 2 B+CI HPLC Kinetic analysis with cerebellum as the reference tissue

  • 2-[18F]FA is safe and efficacious for brain imaging in monkeys.
Chefer et al., 2008 Rhesus monkeys (Macaca mulatta) 3 [18F]NIDA522131 and 2-[18F]FA 540 3 B HPLC Kinetic analysis with BioMedical Image Quantification Software PMOD Version 2.75 (PMOD Technologies, Zurich, Switzerland)

  • [18 F]NIDA522131 is safe and efficacious for brain imaging in monkeys.
Colloby et al., 2008 Humans (Homo sapiens) 9 (4 AD, 5 DLB) 5-[123I]IA before and after administration of donepezil 120 B none SPM2

  • Donepezil produces no change in binding of 5-[123I]IA.
Cosgrove et al., 2007 Humans (Homo sapiens) 29 nonsmokers (10 men, 19 women) 5-[123I]IA during early follicular and mid-luteal phases in women 480 B + CI HPLC MEDx software (Medical Numerics, Inc.)

  • 5-[123I]IA binding is unaffected by sex and menstrual phase.

    5-[123I]IA metabolism and plasma protein binding are greater in women than in men.
Ding et al., 2000 Baboons (Papio anubis) 1 2-[18F]FA and 6-[18F]FA 180 B HPLC Kinetic analysis

  • Metabolism of 6-[18F]FA is faster than 2-[18F]FA in a baboon..
Dollé et al., 1999 Baboons (Papio papio) and Rhesus monkey (Macaca mulatta) 1 baboon and 1 monkey 2-[18F]FA; 5-[123I]IA; [18F]fluoronorchloroepibatidine 90 B HPLC Kinetic analysis

  • In baboons 2-[18F]FA has lower peaks than [18F]fluoronorchloroepibatidine.

    In a monkey 2-[18F]FA has lower peaks than 5-[123I]IA.
Fujita et al., 2006 Humans (Homo sapiens) 15 healthy; 10 PD 5-[123I]IA 230 B HPLC Kinetic analysis

  • Humans with early to moderate PD without dementia demonstrate widespread decrements un the density of nAChRs.
Fujita et al., 2002 Humans (Homo sapiens) 10 5-[123I]IA 1440 B HPLC Kinetic analysis

  • 5-[123I]IA is safe, efficacious in humans.
Fujita et al., 2000 Baboons 3 5-[123I]IA 289–495 B, B + CI HPLC Kinetic analysis 5-[123I]IA is safe, efficacious in baboons.
Gallezot et al., 2005 Humans (Homo sapiens) 7 nonsmokers 2-[18F]FA 210 B HPLC Kinetic analysis

  • 2-[18F]FA is safe and efficacious in humans.
Horti et al., 2000 Rhesus monkeys (Macaca mulatta) 2 6-[18F]FA 270 B HPLC Kinetic analysis

  • 6-[18F]FA is safe and efficacious for brain imaging in monkeys.
Ishizu et al., 2004 Humans (Homo sapiens) 4 5-[123I]IA 360 B Arterial blood sampling Kinetic analysis

  • 5-[123I]IA is safe, efficacious in humans.
Kassiou et al., 2001 Baboons (Papio hamadryas) 2 5-[123I]IA 180 B Plasma metabolite analysis Kinetic analysis

  • Chronic (−)-nicotine treatment upregulates α4β2* nAChRs in baboons.
Kassiou et al., 2002 Baboons (Papio papio) 3 [76Br]BrPH 132 to 240 B Plasma metabolite analysis Kinetic analysis [76Br]BrPH is safe and efficacious in baboons.
Kimes et al., 2003 Humans (Homo sapiens) and Rhesus monkeys (Macaca mulatta) 6 humans and 2 monkeys 2-[18F]FA 420 to 480 B Plasma metabolite analysis Kinetic analysis

  • 2-[18F]FA is safe and efficacious in monkeys and humans.
Mamede et al., 2004 Humans (Homo sapiens) 21 humans 5-[123I]IA 90 or 360 B TLC Kinetic analysis

  • 5-[123I]IA is safe, efficacious in humans.
Mamede et al., 2007 Humans (Homo sapiens) 16 (6 nonsmokers and 10 smoders) 5-[123I]IA 360 B TLC Kinetic analysis

  • Upregulation of α4β2* nAChRs in humans subsides after 21 days of abstinence from cigarette smoking.
Mitkovski et al., 2005 Humans (Homo sapiens) 10 2-[18F]FA 120 B Arterial blood sampling Kinetic analysis

  • Cortical α4β2* nAChRs in humans can be estimated from a single PET acquisition of 120 minutes.
Mitsis et al., 2007 Humans (Homo sapiens) unknown 5-[123I]IA 480 B + CI Venous sampling Kinetic analysis

  • α4β2* nAChRs binding declines with age in humans.
O’Brien et al., 2007 Humans (Homo sapiens) 32 (16 healthy and 16 AD) 5-[123I]IA 150 B HPLC Kinetic analysis

  • α4β2* nAChRs binding is reduced in humans with AD.
Obrzut et al., 2005 Humans (Homo sapiens) 2 2-[18F]FA 180 B plasma sampling Kinetic analysis

  • 2-[18F]FA is safe and efficacious in humans.
Oishi et al., 2006, 2007 Humans (Homo sapiens) 10 healthy and 10 PD 5-[123I]IA 240 B Arterial blood sampling Kinetic analysis

  • α4β2* nAChRs binding is reduced in humans with PD.
Picard et al., 2006 Humans (Homo sapiens) 7 healthy and 8 ADNFLE 2-[18F]FA 240 B Venous plasma sampling SPM2

  • α4β2* nAChRs binding is increased in the epithalamus, ventral mesencephalon, and cerebellum, but decreased in the right dorsolateral prefrontal region in ADNFLE.
Saji et al., 2002 Common marmoset (Callithrix jacchus)I 1 5-[123I]IA 240 B Venous plasma sampling Kinetic analysis

  • 5-[123I]IA is safe, efficacious in a marmoset.
Sorger et al., 2007 Humans (Homo sapiens) 12 healthy and 97 patients with neurological disorders 2-[18F]FA 420 B HPLC or TLC Kinetic analysis

  • α4β2* nAChRs binding is decreased in degenerative neurological disorders.
Staley et al., 2005 Humans (Homo sapiens) 10 5-[123I]IA 420 B + CI Plasma sampling SPM99

  • 5-[123I]IA is safe, efficacious in humans.
Staley et al., 2006 Humans (Homo sapiens) and Rhesus monkeys (Macaca mulatta) 32 humans (16 nonsmokers and 16 smokers) and two monkeys 5-[123I]IA 480 B + CI Plasma sampling Kinetic analysis

  • α4β2* nAChRs binding is increased in the cerebral cortex of recently abstinent smokers.
Ueda et al., 2004 Humans (Homo sapiens) 4 5-[123I]IA 1440 B Plasma sampling Kinetic analysis

  • 5-[123I]IA is safe, efficacious in humans.
Valette et al., 1999 Baboons (Papio papio) 3 2-[18F]FA 180 B Plasma sampling Kinetic analysis

  • 5-[123I]IA is safe, efficacious in baboonns.
Wüllner et al., 2007 Humans (Homo sapiens) 14 (7 nonsmokers and 7 smokers) 2-[18F]FA 364 CI HPLC SPM2

  • α4β2* nAChRs binding is increased in the cerebellum and brainstem of smokers.
Yoshida et al., 2002 Humans (Homo sapiens) 6 healthy and 5 AD 5-[123I]IA 60 CI Arterial blood sampling Kinetic analysis

  • α4β2* nAChRs binding is decreased in the cerebral cortex, the thalamus, and the cerebellum in AD.

[76Br]BrPH = [76Br]norchlorobromoepibatidine; [18F]NCFHEB = [18F]norchloro-fluoro-homoepibatidine; [18F]NIDA522131 = chloro-3-((2-(S)-azetidinyl)methoxy)-5-(2-[18F]fluoropyridin-4-yl)pyridine; 2-[18F]FA = 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine; 5-[123I]IA = (S)-5-[123I]iodo-3-(2-azetidinylmethoxy)pyridine; 6-[18F]FA = 6-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine; AD = Alzheimer’s disease; ADNFLE = autosomal dominant nocturnal frontal lobe epilepsy; B = bolus; B + CI = bolus and continuous infusion; CI = continuous infusion; DLB = dementia with Lewy bodies; DV = distribution volume; HPLC = high performance lipid chromatography; nAChRs = nicotinic acetylcholine receptors; PD = Parkinson’s disease; PET = positron emission tomography; SPECT = single photon emission computed tomography; SPM2 = Statistical Parametric Mapping 2 (http://www.fil.ion.ucl.ac.uk/spm/); SPM99 = Statistical Parametric Mapping, version 99; TLC = thin layer chromatography.