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@article{Dubash:2020:10.1007/s00259-020-04724-y,
author = {Dubash, S and Keat, N and Kozlowski, K and Barnes, C and Allott, L and Brickute, D and Hill, S and Huiban, M and Barwick, T and Kenny, L and Aboagye, E},
doi = {10.1007/s00259-020-04724-y},
journal = {European Journal of Nuclear Medicine and Molecular Imaging},
pages = {2549--2561},
title = {Clinical translation of 18F-fluoropivalate – a PET tracer for imaging short-chain fatty acid metabolism: safety, biodistribution, and dosimetry in fed and fasted healthy volunteers},
url = {http://dx.doi.org/10.1007/s00259-020-04724-y},
volume = {47},
year = {2020}
}

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TY - JOUR
AB - BackgroundFatty acids derived de novo or taken up from the extracellular space are an essential source of nutrient for cell growth and proliferation. Radiopharmaceuticals including 11C-acetate, and 18F-FAC (2-18F-fluoroacetate), have previously been used to study short-chain fatty acid (SCFA) metabolism. We developed 18F-fluoropivalate (18F-FPIA; 3-18F-fluoro-2,2-dimethylpropionic acid) bearing a gem-dimethyl substituent to assert metabolic stability for studying SCFA metabolism. We report the safety, biodistribution, and internal radiation dosimetry profile of 18F-FPIA in 24 healthy volunteers and the effect of dietary conditions.Materials and methodsHealthy volunteer male and female subjects were enrolled (n = 24), and grouped into 12 fed and 12 fasted. Non-esterified fatty acids (NEFA) and carnitine blood measurements were assessed. Subjects received 159.48 MBq (range, 47.31–164.66 MBq) of 18F-FPIA. Radiochemical purity was > 99%. Safety data were obtained during and 24 h after radiotracer administration. Subjects underwent detailed multiple whole-body PET/CT scanning with sampling of venous bloods for radioactivity and radioactive metabolite quantification. Regions of interest were defined to derive individual and mean organ residence times; effective dose was calculated using OLINDA 1.1.ResultsAll subjects tolerated 18F-FPIA with no adverse events. Over 90% of radiotracer was present in plasma at 60 min post-injection. The organs receiving highest absorbed dose (in mGy/MBq) were the liver (0.070 ± 0.023), kidneys (0.043 ± 0.013), gallbladder wall (0.026 ± 0.003), and urinary bladder (0.021 ± 0.004); otherwise there was low tissue uptake. The calculated effective dose using mean organ residence times over all 24 subjects was 0.0154 mSv/MBq (SD ± 0.0010). No differences in biodistribution or dosimetry were seen in fed and fasted subjects
AU - Dubash,S
AU - Keat,N
AU - Kozlowski,K
AU - Barnes,C
AU - Allott,L
AU - Brickute,D
AU - Hill,S
AU - Huiban,M
AU - Barwick,T
AU - Kenny,L
AU - Aboagye,E
DO - 10.1007/s00259-020-04724-y
EP - 2561
PY - 2020///
SN - 1619-7070
SP - 2549
TI - Clinical translation of 18F-fluoropivalate – a PET tracer for imaging short-chain fatty acid metabolism: safety, biodistribution, and dosimetry in fed and fasted healthy volunteers
T2 - European Journal of Nuclear Medicine and Molecular Imaging
UR - http://dx.doi.org/10.1007/s00259-020-04724-y
UR - http://hdl.handle.net/10044/1/78000
VL - 47
ER -

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