Biodistribution and radiation dosimetry of 18F-fluoro-A-85380 in healthy volunteers.
This study reports on the biodistribution and radiation dosimetry of 2-(18)F-Fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine ((18)F-fluoro-A-85380), a promising radioligand for the imaging of central nicotinic acetylcholine receptors (nAChRs).


METHODS
Whole-body scans were performed in 3 healthy male volunteers up to 2 h after intravenous injection of 137-238 MBq (18)F-fluoro-A-85380. Transmission scans (3 min per step, 8 or 9 steps according to the height of the subject) in 2-dimensional mode were used for subsequent correction of attenuation of emission scans. Emission scans (1 min per step) were acquired over 2 h. Venous blood samples were taken up to 2 h after injection of the radiotracer. Urine was freely collected up to 2 h after injection of the radiotracer. For each subject, the percentage of injected activity measured in regions of interest over brain, intestine, stomach, bladder, kidneys, and liver were fitted to a monoexponential model, as an uptake phase followed by a monoexponential washout, or to a biexponential model to generate time-activity curves. Using the MIRD method, ten source organs were considered in estimating radiation absorbed doses for organs of the body.


RESULTS
Injection of (18)F-fluoro-A-85380 was clinically well tolerated and blood and urine pharmacologic parameters did not change significantly. The primary routes of clearance were renal and intestinal. Ten minutes after injection, high activities were observed in the bladder, kidneys, and liver. Slow uptake was seen in the brain. The liver received the highest absorbed dose. The average effective dose of (18)F-fluoro-A-85380 was estimated to be 0.0194 mSv/MBq.


CONCLUSIONS
The amount of (18)F-fluoro-A-85380 required for adequate nAChR imaging results in an acceptable effective dose equivalent to the patient.
Bottlaender
Michel
M
Department of Medical Research, Division of Life Sciences, Service Hospitalier Frédéric Joliot, French Atomic Agency, 4 Place du Général Leclerc, F-91406 Orsay, France.
Valette
Héric
H
Roumenov
Dimitri
D
Dollé
Frédéric
F
Coulon
Christine
C
Ottaviani
Michèle
M
Hinnen
Françoise
F
Ricard
Marcel
M
D000042:Absorption; D000328:Adult; D001384:Azetidines; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009928:Organ Specificity; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011829:Radiation Dosage; D011874:Radiometry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*; D014915:Whole-Body Counting
C119803:2-fluoro-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D011725:Pyridines; D019275:Radiopharmaceuticals