RT Journal Article
SR Electronic
T1 Biodistribution and Radiation Dosimetry of Deuterium-Substituted <sup>18</sup>F-Fluoromethyl-[1, 2-<sup>2</sup>H<sub>4</sub>]Choline in Healthy Volunteers
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 256
OP 263
DO 10.2967/jnumed.113.129577
VO 55
IS 2
A1 Challapalli, Amarnath
A1 Sharma, Rohini
A1 Hallett, William A.
A1 Kozlowski, Kasia
A1 Carroll, Laurence
A1 Brickute, Diana
A1 Twyman, Frazer
A1 Al-Nahhas, Adil
A1 Aboagye, Eric O.
YR 2014
UL http://jnm.snmjournals.org/content/55/2/256.abstract
AB 11C-choline and 18F-fluoromethylcholine (18F-FCH) have been used in patients to study tumor metabolic activity in vivo; however, both radiotracers are readily oxidized to respective betaine analogs, with metabolites detectable in plasma soon after injection of the radiotracer. A more metabolically stable FCH analog, 18F-fluoromethyl-[1,2-2H4]choline (18F-D4-FCH), based on the deuterium isotope effect, has been developed. We report the safety, biodistribution, and internal radiation dosimetry profiles of 18F-D4-FCH in 8 healthy human volunteers. Methods: 18F-D4-FCH was intravenously administered as a bolus injection (mean ± SD, 161 ± 2.17 MBq; range, 156–163 MBq) to 8 healthy volunteers (4 men, 4 women). Whole-body (vertex to mid thigh) PET/CT scans were acquired at 6 time points, up to 4 h after tracer injection. Serial whole-blood, plasma, and urine samples were collected for radioactivity measurement and plasma radiotracer metabolites. Tissue 18F radioactivities were determined from quantitative analysis of the images, and time–activity curves were generated. The total numbers of disintegrations in each organ normalized to injected activity (residence times) were calculated as the area under the curve of the time–activity curve normalized to injected activities and standard organ volumes. Dosimetry calculations were performed using OLINDA/EXM 1.1. Results: The injection of 18F-D4-FCH was well tolerated in all subjects, with no radiotracer-related serious adverse event reported. The mean effective dose averaged over both men and women (±SD) was estimated to be 0.025 ± 0.004 (men, 0.022 ± 0.002; women, 0.027 ± 0.002) mSv/MBq. The 5 organs receiving the highest absorbed dose (mGy/MBq) were the kidneys (0.106 ± 0.03), liver (0.094 ± 0.03), pancreas (0.066 ± 0.01), urinary bladder wall (0.047 ± 0.02), and adrenals (0.046 ± 0.01). Elimination was through the renal and hepatic systems. Conclusion: 18F-D4-FCH is a safe PET radiotracer with a dosimetry profile comparable to other common 18F PET tracers. These data support the further development of 18F-D4-FCH for clinical imaging of choline metabolism.