Nifene

Nifene is a high affinity, selective nicotinic α4β2* receptor partial agonist used in medical research for nicotinic acetylcholine receptors, usually in the form of nifene (18F)[1][2] as a positron emission tomography (PET) radiotracer.[3][4]

Nifene (18F)
Clinical data
ATC code
  • None
Legal status
Legal status
  • Research compound
Identifiers
  • 3-[(2S)-2,5-Dihydro-1H-pyrrol-2-ylmethoxy]-2-18F-fluoropyridine
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC10H11FN2O
Molar mass194.209 g·mol−1
3D model (JSmol)
  • C1C=C[C@H](N1)COC2=C(N=CC=C2)[18F]
  • InChI=1S/C10H11FN2O/c11-10-9(4-2-6-13-10)14-7-8-3-1-5-12-8/h1-4,6,8,12H,5,7H2/t8-/m0/s1/i11-1
  • Key:GHHQHFNDKOQCRS-IZFLLFDKSA-N

Nifene has been used to assess the efficacy of acetylcholinesterase inhibitors in animal models, because the neurotransmitter acetylcholine competes with the binding of nifene at the nicotinic receptor site.[5][6] Learning and behavior studies in animal models using nifene have suggested a potential role of the nicotinic receptors located in distinct white matter tracts.[7] Nifene studies in animal models of lung cancer have suggested an upregulation of the nicotinic receptor in the lung tumors.[8][9] Novel PET and SPECT imaging agents as potential receptor antagonists have been developed based on the structure of nifene; niodene for SPECT,[10] nifrolene for PET [11] and niofene for PET/SPECT.[12] These new derivatives take advantage of the unique in vivo imaging properties of nifene.[13] Human studies with (18F)-nifene make it a promising nicotinic α4β2* receptor PET radiotracer for scientific research and has exhibited reliable test-retest reproducibility.[14] Human white matter thalamic radiations (or tracts) were well demarcated and quantified using (18F)-nifene.[15]

References
  1. Pichika R, Easwaramoorthy B, Collins D, Christian BT, Shi B, Narayanan TK, et al. (April 2006). "Nicotinic alpha4beta2 receptor imaging agents: part II. Synthesis and biological evaluation of 2-[18F]fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (18F-nifene) in rodents and imaging by PET in nonhuman primate". Nuclear Medicine and Biology. 33 (3): 295–304. doi:10.1016/j.nucmedbio.2005.12.017. PMID 16631077.
  2. Leung K (2004). "2-18FFluoro-3-2-((S)-3-pyrrolinyl)methoxypyridine". PMID 20641387. {{cite journal}}: Cite journal requires |journal= (help)
  3. Kant R, Constantinescu CC, Parekh P, Pandey SK, Pan ML, Easwaramoorthy B, Mukherjee J (June 2011). "Evaluation of F-nifene binding to α4β2 nicotinic receptors in the rat brain using microPET imaging". EJNMMI Research. 1: 6. doi:10.1186/2191-219X-1-6. PMC 3203019. PMID 22039577.
  4. Hillmer AT, Wooten DW, Slesarev MS, Ahlers EO, Barnhart TE, Murali D, et al. (September 2012). "PET imaging of α4β2* nicotinic acetylcholine receptors: quantitative analysis of 18F-nifene kinetics in the nonhuman primate". Journal of Nuclear Medicine. 53 (9): 1471–80. doi:10.2967/jnumed.112.103846. PMC 3580212. PMID 22851633.
  5. Easwaramoorthy B, Pichika R, Collins D, Potkin SG, Leslie FM, Mukherjee J (January 2007). "Effect of acetylcholinesterase inhibitors on the binding of nicotinic alpha4beta2 receptor PET radiotracer, (18)F-nifene: A measure of acetylcholine competition". Synapse. 61 (1): 29–36. doi:10.1002/syn.20338. PMID 17068780. S2CID 85303757.
  6. Hillmer AT, Wooten DW, Farhoud M, Higgins AT, Lao PJ, Barnhart TE, et al. (December 2013). "PET imaging of acetylcholinesterase inhibitor-induced effects on α4β2 nicotinic acetylcholine receptor binding". Synapse. 67 (12): 882–6. doi:10.1002/syn.21698. PMC 3806056. PMID 23913347.
  7. Bieszczad KM, Kant R, Constantinescu CC, Pandey SK, Kawai HD, Metherate R, et al. (May 2012). "Nicotinic acetylcholine receptors in rat forebrain that bind 18F-nifene: relating PET imaging, autoradiography, and behavior". Synapse. 66 (5): 418–34. doi:10.1002/syn.21530. PMC 3292694. PMID 22213342.
  8. Galitovskiy V, Kuruvilla SA, Sevriokov E, Corches A, Pan ML, Kalantari-Dehaghi M, et al. (June 2013). "18F-Nifene PET/CT using A/J mice treated with NNK". Journal of Cancer Research & Therapy. 1 (4): 128–137. doi:10.14312/2052-4994.2013-20. PMC 5443253. PMID 28553544.
  9. Tang W, Kuruvilla SA, Galitovskiy V, Pan ML, Grando SA, Mukherjee J (2014). "Targeting histone deacetylase in lung cancer for early diagnosis: (18)F-FAHA PET/CT imaging of NNK-treated A/J mice model". American Journal of Nuclear Medicine and Molecular Imaging. 4 (4): 324–32. PMC 4074498. PMID 24982818.
  10. Pandey SK, Pan S, Kant R, Kuruvilla SA, Pan ML, Mukherjee J (December 2012). "Synthesis and evaluation of 3-123I-iodo-5-[2-(S)-3-pyrrolinylmethoxy]-pyridine (niodene) as a potential nicotinic α4β2 receptor imaging agent". Bioorganic & Medicinal Chemistry Letters. 22 (24): 7610–4. doi:10.1016/j.bmcl.2012.10.012. PMC 3508149. PMID 23116890.
  11. Pichika R, Kuruvilla SA, Patel N, Vu K, Sinha S, Easwaramoorthy B, et al. (January 2013). "Nicotinic α4β2 receptor imaging agents. Part IV. Synthesis and biological evaluation of 3-(2-(S)-3,4-dehydropyrrolinyl methoxy)-5-(3'-18F-fluoropropyl)pyridine (18F-Nifrolene) using PET". Nuclear Medicine and Biology. 40 (1): 117–25. doi:10.1016/j.nucmedbio.2012.09.009. PMC 3514651. PMID 23141552.
  12. Kuruvilla SA, Hillmer AT, Wooten DW, Patel A, Christian BT, Mukherjee J (2014). "Synthesis and evaluation of 2-(18)F-fluoro-5-iodo-3-[2-(S)-3,4-dehydropyrrolinylmethoxy]pyridine ((18)F-Niofene) as a potential imaging agent for nicotinic α4β2 receptors". American Journal of Nuclear Medicine and Molecular Imaging. 4 (4): 354–64. PMC 4074501. PMID 24982821.
  13. Hillmer AT, Wooten DW, Slesarev MS, Ahlers EO, Barnhart TE, Schneider ML, et al. (November 2013). "Measuring α4β2* nicotinic acetylcholine receptor density in vivo with [(18)F]nifene PET in the nonhuman primate". Journal of Cerebral Blood Flow and Metabolism. 33 (11): 1806–14. doi:10.1038/jcbfm.2013.136. PMC 3824181. PMID 23942367.
  14. Lao PJ, Betthauser TJ, Tudorascu DL, Barnhart TE, Hillmer AT, Stone CK, Mukherjee J, Christian BT (August 2017). "[18 F]Nifene test-retest reproducibility in first-in-human imaging of α4β2* nicotinic acetylcholine receptors". Synapse. New York, N.Y. 71 (8): e21981. doi:10.1002/syn.21981. PMC 5541262. PMID 28420041.
  15. Mukherjee J, Lao PJ, Betthauser TJ, Samra GK, Pan ML, Patel IH, Liang C, Metherate R, Christian BT (January 2018). "Human brain imaging of nicotinic acetylcholine α4β2* receptors using [18 F]Nifene: Selectivity, functional activity, toxicity, aging effects, gender effects, and extrathalamic pathways". The Journal of Comparative Neurology. 526 (1): 80–95. doi:10.1002/cne.24320. PMC 5788574. PMID 28875553.
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