title: Whole-body biodistribution, radiation absorbed dose, and brain SPET imaging with [123i]5-i-A-85380 in healthy human subjects.
abstract: The biodistribution of radioactivity after the administration of a new tracer for alpha4beta2 nicotinic acetylcholine receptors (nAChRs), [123I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), was studied in ten healthy human subjects. Following administration of 98+/-6 MBq [123I]5-I-A-85380, serial whole-body images were acquired over 24 h and corrected for attenuation. One to four brain single-photon emission tomography (SPET) images were also acquired between 2.5 and 24 h. Estimates of radiation absorbed dose were calculated using MIRDOSE 3.1 with a dynamic bladder model and a dynamic gastrointestinal tract model. The estimates of the highest absorbed dose (microGy/MBq) were for the urinary bladder wall (71 and 140), lower large intestine wall (70 and 72), and upper large intestine wall (63 and 64), with 2.4-h and 4.8-h urine voiding intervals, respectively. The whole brain activity at the time of the initial whole-body imaging at 14 min was 5.0% of the injected dose. Consistent with the known distribution of alpha4beta2 nAChRs, SPET images showed the highest activity in the thalamus. These results suggest that [123I]5-I-A-85380 is a promising SPET agent to image alpha4beta2 nAChRs in humans, with acceptable dosimetry and high brain uptake.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine and VA Connecticut Healthcare System, VA Connecticut/116A2, West Haven 06516, USA. masahiro.fujita@yale.edu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujita
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: D Bruce
authors.initials: DB
authors.lastname: Vaupel
authors.forename: Gilles
authors.initials: G
authors.lastname: Tamagnan
authors.forename: Michele
authors.initials: M
authors.lastname: Early
authors.forename: Sami S
authors.initials: SS
authors.lastname: Zoghbi
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Horti
authors.forename: Andrei O
authors.initials: AO
authors.lastname: KoreN
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Mukhin
authors.forename: Shaukat
authors.initials: S
authors.lastname: Khan
authors.forename: Ali
authors.initials: A
authors.lastname: Bozkurt
authors.forename: Alane S
authors.initials: AS
authors.lastname: Kimes
authors.forename: Edythe D
authors.initials: ED
authors.lastname: London
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000328:Adult; D001384:Azetidines / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008297:Male; D011725:Pyridines / Q000493:pharmacokinetics; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C426745:5-iodo-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D007457:Iodine Radioisotopes; D011725:Pyridines; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2