Exploration of the Dopamine Transporter: In Vitro and In Vivo Characterization of a High-Affinity and High-Specificity Iodinated Tropane Derivative (E)-N-(3-iodoprop-2-enyl)-2β-carbomethoxy- 3β-(4′-methylphenyl)nortropane (PE2I)

Pharmacological Characterization of (E)-N-(4-Fluorobut-2-enyl)-2β-carbomethoxy-3β-(4′-tolyl)nortropane (LBT-999) as a Highly Promising Fluorinated Ligand for the Dopamine Transporter

“…In a first step, ex vivo cerebral biodistribution in rats demonstrated that the ligand had a rapid and high entry into the brain where its distribution was in agreement with specific binding to the DAT. The brain entrance of LBT-999 in rats (mean value of 4.95% ID/g in the striatum at 30 min postinjection) was higher than that for PE2I (1.06% in same experimental design) (Guilloteau et al, 1998), as well as the striatum/cerebellum ratio (18 for LBT-999 versus 10 for PE2I). The striatal accumulation of LBT-999 was around 70% decreased in the presence of a saturating dose of GBR 12909, as already observed for PE2I.…”

Dopamine D2/D3-receptor and transporter densities in nucleus accumbens and amygdala of type 1 and 2 alcoholics

“…Incubation time to reach equilibrium was chosen to be 1 h according to earlier studies with these same ligands. 22,23,26,27 The first series of sections (eight controls, seven type 1 alcoholics, six type 2 alcoholics) were incubated in a solution (volume 2.5 l) containing approximately 24 pM of [ 125 I]epidepride (the incubation concentration) in Tris-HCl buffer, pH 7.4, 0.05 M, containing 0.1% (weight/volume) ascorbic acid, 120 mM NaCl, 5 mM KCl, 2 mM CaCl 2 , and 1 mM MgCl 2 . (+)-Butaclamol (15 M) was used as a specific displacer to determine nonspecific binding.…”

“…[17][18][19][20][21] The radioligand [ 125 I]epidepride ((S)-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-iodo-2,3, dimethoxybenzamine) has a very high affinity for DA D 2 receptors, with very low non-specific binding, and has been widely used to label DA D 2 receptors in the human brain. 22,23 It also binds to DA D 3 22 [ 125 I]PE2I ((E)-N-(3-iodoprop-2E-enyl)-2␤-carbomethoxy-3␤-(4Ј-methylphenyl) nortropane) is a novel radioligand ligand having high selectivity and affinity for DAT, [24][25][26] and has been previously used for imaging DAT both in vitro and in vivo. [24][25][26][27] It has 30-and Ͼ60-fold selectivities in vitro over serotonin and noradrenalin transporters, respectively, 25,26 which makes it far superior to older cocaine derivatives like ␤-CIT, frequently used in previous in vivo studies.…”

“…22,23 It also binds to DA D 3 22 [ 125 I]PE2I ((E)-N-(3-iodoprop-2E-enyl)-2␤-carbomethoxy-3␤-(4Ј-methylphenyl) nortropane) is a novel radioligand ligand having high selectivity and affinity for DAT, [24][25][26] and has been previously used for imaging DAT both in vitro and in vivo. [24][25][26][27] It has 30-and Ͼ60-fold selectivities in vitro over serotonin and noradrenalin transporters, respectively, 25,26 which makes it far superior to older cocaine derivatives like ␤-CIT, frequently used in previous in vivo studies. Such radioligands in human post-mortem whole hemispheric autoradiography provide high resolution images from different brain levels, to compare with in vivo studies (ie, PET and SPET) and enable a more detailed study of various structures.…”

Measurement of Striatal and Extrastriatal Dopamine Transporter Binding with High-Resolution PET and [11C]PE2I: Quantitative Modeling and Test—Retest Reproducibility

“…Introduction N-(3-iodoprop-2E-enyl)-2b-carbomethoxy-3b-(4-methylphenyl)nortropane (PE2I) is a recently developed cocaine analog having nanomolar affinity for dopamine transporter (DAT) in vitro (Emond et al, 1997;Guilloteau et al, 1998;Page et al, 2002). The main advantage of PE21 when compared with previous DAT ligands is the high (over 30-fold) selectivity for DAT over the norepinephrine transporter and serotonin transporter.…”