Quantification of nicotinic acetylcholine receptors in human brain using [123I]5-I-A-85380 SPET

• Published in: European journal of nuclear medicine and molecular imaging 2003-12, Vol.30 (12), p.1620-1629
• Main Authors: FUJITA, Masahiro, ICHISE, Masanori, LIDA, Hidehiro, VAUPEL, D. Bruce, HORTI, Andrew G, KOREN, Andrei O, KIMES, Alane S, LONDON, Edythe D, SEIBYL, John P, BALDWIN, Ronald M, INNIS, Robert B, VAN DYCK, Christopher H, ZOGHBI, Sami S, TAMAGNAN, Gilles, MUKHIN, Alexey G, BOZKURT, Ali, SENECA, Nicholas, TIPRE, Dnyanesh, DENUCCI, Christopher C
• Format: Article
• Language: English
• Subjects: Adult; Azetidines - administration & dosage; Azetidines - blood; Azetidines - pharmacokinetics; Biological and medical sciences; Brain - diagnostic imaging; Brain - metabolism; Female; Humans; Image Interpretation, Computer-Assisted - methods; Infusions, Intravenous; Injections, Intravenous; Male; Medical sciences; Metabolic Clearance Rate; Models, Biological; Pyridines - administration & dosage; Pyridines - blood; Pyridines - pharmacokinetics; Radiopharmaceuticals - administration & dosage; Radiopharmaceuticals - blood; Radiopharmaceuticals - pharmacokinetics; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Receptors, Cholinergic - metabolism; Reproducibility of Results; Sensitivity and Specificity; Technology. Biomaterials. Equipments. Material. Instrumentation; Tissue Distribution; Tomography, Emission-Computed, Single-Photon - methods
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-003-1320-0

The purpose of this study was to assess the utility of a new single-photon emission tomography ligand, [123I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), to measure regional nAChR binding in human brain. Six healthy nonsmoker subjects (two men and four women, age 33 +/- 15 years) participated in both a bolus (dose: 317 +/- 42 MBq) and a bolus plus constant infusion (dose of bolus: 98 +/- 32 MBq, B/I=6.7 +/- 2.6 h, total dose: 331 +/- 55 MBq) study. The study duration was 5-8 h and 14 h in the former and the latter, respectively. Nonlinear least-squares compartmental analysis was applied to bolus studies to calculate total (VT') and specific (VS') distribution volumes. A two-tissue compartment model was applied to identify VS'. VT' was also calculated in B/I studies. In bolus studies, VT' was well identified by both one- and two-tissue compartment models, with a coefficient of variation of less than 5% in most regions. The two-compartment model gave VT' values of 51, 22, 27, 32, 20, 19, 20, and 17 ml cm(-3) in thalamus, cerebellum, putamen, pons, and frontal, parietal, temporal, and occipital cortices, respectively. The two-compartment model did not identify VS' well. B/I studies provided poor accuracy of VT' measurement, possibly due to deviations from equilibrium conditions. These results demonstrate the feasibility of quantifying high-affinity type nAChRs using [123I]5-I-A-85380 in humans and support the use of VT' measured by bolus studies.