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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

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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
Authors: Dubash, S
Keat, N
Kozlowski, K
Barnes, C
Allott, L
Brickute, D
Hill, S
Huiban, M
Barwick, T
Kenny, L
Aboagye, E
Item Type: Journal Article
Abstract: Background Fatty 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 methods Healthy 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. Results All 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, though systemic NEFA and carnitine levels reflected fasted and fed states. Conclusion The favourable safety, imaging, and dosimetric profile makes 18F-FPIA a promising candidate radiotracer for tracing SCFA metabolism.
Issue Date: 1-Oct-2020
Date of Acceptance: 14-Feb-2020
URI: http://hdl.handle.net/10044/1/78000
DOI: 10.1007/s00259-020-04724-y
ISSN: 1619-7070
Publisher: Springer Verlag
Start Page: 2549
End Page: 2561
Journal / Book Title: European Journal of Nuclear Medicine and Molecular Imaging
Volume: 47
Copyright Statement: © 2020 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: MR/N020782/1
RDC04
Keywords: Science & Technology
Life Sciences & Biomedicine
Radiology, Nuclear Medicine & Medical Imaging
F-18-Fluoropivalate
F-18-FPIA
Positron emission tomography
Short chain fatty acid metabolism
Dosimetry
Carnitine
ACETATE
ANALOG
AGENT
18F-FPIA
18F-Fluoropivalate
Carnitine
Dosimetry
Positron emission tomography
Short chain fatty acid metabolism
Nuclear Medicine & Medical Imaging
0299 Other Physical Sciences
1103 Clinical Sciences
Publication Status: Published
Online Publication Date: 2020-03-02
Appears in Collections:Department of Surgery and Cancer
Faculty of Medicine