title: Small-animal single-photon emission computed tomographic imaging of the brain serotoninergic systems in wild-type and mdr1a knockout rats.
abstract: The pharmacokinetic properties of radiotracers are crucial for successful in vivo single-photon emission computed tomographic (SPECT) imaging. Our goal was to determine if MDR1A-deficient animals could allow better SPECT imaging outcomes than wild-type (WT) animals for a selection of serotoninergic radioligands. Thus, we compared the performances of 123I-p-MPPI, 123I-R91150, 123I-SB207710, and 123I-ADAM radioligands, for imaging of their respective targets (5-hydroxytryptamine [5-HT]1A, 5-HT2A, 5-HT4, and serotonin transporter [SERT]), in WT and Mdr1a knockout (KO) rats. With 123I-SB207710, virtually no SPECT signal was recorded in the brain of WT or KO animals. For 123I-p-MPPI, low nondisplaceable binding potentials (BPND, mean ± SD) were observed in WT (0.49 ± 0.25) and KO (0.89 ± 0.52) animals. For 123I-ADAM, modest imaging contrast was observed in WT (1.27 ± 0.02) and KO (1.31 ± 0.09) animals. For 123I-R91150, the BPND were significantly higher in Mdr1a KO (3.98 ± 0.65) animals compared to WT animals (1.22 ± 0.26). The pharmacokinetics of 123I-SB207710 and 123I-p-MPPI do not make them ideal tracers for preclinical SPECT neuroimaging. 123I-ADAM showed adequate brain uptake regardless of Mdr1a expression and appeared suitable for preclinical SPECT neuroimaging in both animal strains. The use of Mdr1a KO animals significantly improved the brain penetration of 123I-R91150, making this animal strain an interesting option when considering SPECT neuroimaging of 5-HT2A receptors in rat.
authors.forename: Noé
authors.initials: N
authors.lastname: Dumas
authors.forename: Marcelle
authors.initials: M
authors.lastname: Moulin-Sallanon
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ginovart
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Tournier
authors.forename: Peggy
authors.initials: P
authors.lastname: Suzanne
authors.forename: Thomas
authors.initials: T
authors.lastname: Cailly
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fabis
authors.forename: Sylvain
authors.initials: S
authors.lastname: Rault
authors.forename: Yves
authors.initials: Y
authors.lastname: Charnay
authors.forename: Philippe
authors.initials: P
authors.lastname: Millet
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics* / Q000378:metabolism; D000631:Aminopyridines / Q000493:pharmacokinetics; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002928:Cinanserin / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D055786:Gene Knockout Techniques; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D008297:Male; D009928:Organ Specificity; D010879:Piperazines / Q000493:pharmacokinetics; D010880:Piperidines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000631:Aminopyridines; D002928:Cinanserin; D007457:Iodine Radioisotopes; D010879:Piperazines; D010880:Piperidines; D019275:Radiopharmaceuticals; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C413491:2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine; C105020:R 91150; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; C095122:multidrug resistance protein 3