Whole-body biodistribution, radiation absorbed dose, and brain SPET imaging with [123I]5-I-A-85380 in healthy human subjects

• Published in: European journal of nuclear medicine Vol. 29; no. 2; pp. 183 - 190
• Main Authors: Fujita, Masahiro, Seibyl, John P., Vaupel, Bruce D., Tamagnan, Gilles, Early, Michele, Zoghbi, Sami S., Baldwin, Ronald M., Horti, Andrew G., Koren, Andrei O., Mukhin, Alexey G., Khan, Shaukat, Bozkurt, Ali, Kimes, Alane S., London, Edythe D., Innis, Robert B.
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.02.2002; Springer Nature B.V
• Subjects: Adult; Azetidines - pharmacokinetics; Biological and medical sciences; Brain - diagnostic imaging; Brain - metabolism; Contrast media. Radiopharmaceuticals; Female; Humans; Iodine Radioisotopes - pharmacokinetics; Male; Medical sciences; Pharmacology. Drug treatments; Pyridines - pharmacokinetics; Radiation Dosage; Radiopharmaceuticals - pharmacokinetics; Receptors, Nicotinic - metabolism; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Radionuclide study; Human; Biology; Pharmacology; Radioisotope; Radiation absorption; Radiation dose; Distribution; Whole body; Dosimetry; Radiopharmaceuticals; Brain (vertebrata); Iodine ion; Positron; Emission tomography
• ISSN: 1619-7070; 0340-6997; 1619-7089
• DOI: 10.1007/s00259-001-0695-z

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.