UNLABELLED: Previous work on the PET measured uptake of (S)-[11C]nicotine presents conflicting findings as to whether it reflects specific binding. METHODS: We studied the uptake of (R)-[11C]nicotine and (S)-[11C]nicotine in normal volunteers at baseline conditions and after a challenge with unlabeled (S)-nicotine to decrease the concentration of free binding sites or with CO2 to increase perfusion. We analyzed the data using two- and three-compartment models. RESULTS: We found tissue pharmacokinetics of (R)- and (S)-[11C]nicotine are adequately described by the two-compartment model. (S)-nicotine challenge induced small but statistically significant reductions in distribution volume (DV) of both (R)- and (S)-[11C]nicotine. The changes in DV could not be attributed to perfusion changes because DV was not affected by CO2 challenge. Although the reduction in DV indicates sensitivity of [11C]nicotine to status of nicotinic binding sites, the small magnitude of the reduction suggests that most nicotine uptake is nonspecific. CONCLUSION: Although differences in DV attributable to specific binding were detected, (R)- and (S)-[11C]nicotine are relatively poor tracers for studying nicotinic binding sites using PET.
UNLABELLED: Previous work on the PET measured uptake of (S)-[11C]nicotine presents conflicting findings as to whether it reflects specific binding. METHODS: We studied the uptake of (R)-[11C]nicotine and (S)-[11C]nicotine in normal volunteers at baseline conditions and after a challenge with unlabeled (S)-nicotine to decrease the concentration of free binding sites or with CO2 to increase perfusion. We analyzed the data using two- and three-compartment models. RESULTS: We found tissue pharmacokinetics of (R)- and(S)-[11C]nicotine are adequately described by the two-compartment model. (S)-nicotine challenge induced small but statistically significant reductions in distribution volume (DV) of both (R)- and(S)-[11C]nicotine. The changes in DV could not be attributed to perfusion changes because DV was not affected by CO2 challenge. Although the reduction in DV indicates sensitivity of [11C]nicotine to status of nicotinic binding sites, the small magnitude of the reduction suggests that most nicotine uptake is nonspecific. CONCLUSION: Although differences in DV attributable to specific binding were detected, (R)- and(S)-[11C]nicotine are relatively poor tracers for studying nicotinic binding sites using PET.
Authors: Marc S Berridge; Scott M Apana; Kenichi K Nagano; Catherine E Berridge; Gregory P Leisure; Mark V Boswell Journal: Psychopharmacology (Berl) Date: 2010-03-16 Impact factor: 4.530
Authors: Jed E Rose; Alexey G Mukhin; Stephen J Lokitz; Timothy G Turkington; Joseph Herskovic; Frederique M Behm; Sudha Garg; Pradeep K Garg Journal: Proc Natl Acad Sci U S A Date: 2010-03-08 Impact factor: 11.205
Authors: Julie K Staley; Suchitra Krishnan-Sarin; Kelly P Cosgrove; Erica Krantzler; Erin Frohlich; Edward Perry; Joel A Dubin; Kristina Estok; Eric Brenner; Ronald M Baldwin; Gilles D Tamagnan; John P Seibyl; Peter Jatlow; Marina R Picciotto; Edythe D London; Stephanie O'Malley; Christopher H van Dyck Journal: J Neurosci Date: 2006-08-23 Impact factor: 6.167
Authors: Ansel T Hillmer; Dustin W Wooten; Maxim S Slesarev; Elizabeth O Ahlers; Todd E Barnhart; Dhanabalan Murali; Mary L Schneider; Jogeshwar Mukherjee; Bradley T Christian Journal: J Nucl Med Date: 2012-07-31 Impact factor: 10.057