title: High-affinity dopamine D2/D3 PET radioligands 18F-fallypride and 11C-FLB457: a comparison of kinetics in extrastriatal regions using a multiple-injection protocol.
abstract: (18)F-Fallypride and (11)C-FLB457 are commonly used PET radioligands for imaging extrastriatal dopamine D(2)/D(3) receptors, but differences in their in vivo kinetics may affect the sensitivity for measuring subtle changes in receptor binding. Focusing on regions of low binding, a direct comparison of the kinetics of (18)F-fallypride and (11)C-FLB457 was made using a MI protocol. Injection protocols were designed to estimate K(1), k(2), f(ND)k(on), B(max), and k(off) in the midbrain and cortical regions of the rhesus monkey. (11)C-FLB457 cleared from the arterial plasma faster and yielded a ND space distribution volume (K(1)/k(2)) that is three times higher than (18)F-fallypride, primarily due to a slower k(2) (FAL:FLB; k(2)=0.54 min(-1):0.18 min(-1)). The dissociation rate constant, k(off), was slower for (11)C-FLB457, resulting in a lower K(Dapp) than (18)F-fallypride (FAL:FLB; 0.39 nM:0.13 nM). Specific D(2)/D(3) binding could be detected in the cerebellum for (11)C-FLB457 but not (18)F-fallypride. Both radioligands can be used to image extrastriatal D(2)/D(3) receptors, with (11)C-FLB457 providing greater sensitivity to subtle changes in low-receptor-density cortical regions and (18)F-fallypride being more sensitive to endogenous dopamine displacement in medium-to-high-receptor-density regions. In the presence of specific D(2)/D(3) binding in the cerebellum, reference region analysis methods will give a greater bias in BP(ND) with (11)C-FLB457 than with (18)F-fallypride.
authors.affiliation: Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin, USA. nickvandehey@gmail.com
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Vandehey
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Moirano
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Converse
authors.forename: James E
authors.initials: JE
authors.lastname: Holden
authors.forename: Jogesh
authors.initials: J
authors.lastname: Mukherjee
authors.forename: Dhanabalan
authors.initials: D
authors.lastname: Murali
authors.forename: R Jerry
authors.initials: RJ
authors.lastname: Nickles
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Davidson
authors.forename: Mary L
authors.initials: ML
authors.lastname: Schneider
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Christian
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000378:metabolism; D018492:Dopamine Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000378:metabolism; D008024:Ligands; D008253:Macaca mulatta; D049268:Positron-Emission Tomography / Q000379:methods*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012457:Salicylamides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001549:Benzamides; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D005462:Fluorine Radioisotopes; D008024:Ligands; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; C065065:FLB 457