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Development & automation of a novel [(18)F]F prosthetic group, 2-[(18)F]-fluoro-3-pyridinecarboxaldehyde, and its application to an amino(oxy)-functionalised A? peptide.

ABSTRACT: 2-[(18)F]-Fluoro-3-pyridinecarboxaldehyde ([(18)F]FPCA) is a novel, water-soluble prosthetic group. It's radiochemistry has been developed and fully-automated for application in chemoselective radiolabelling of amino(oxy)-derivatised RI-OR2-TAT peptide, (Aoa-k)-RI-OR2-TAT, using a GE TRACERlab FX-FN. RI-OR2-TAT is a brain-penetrant, retro-inverso peptide that binds to amyloid species associated with Alzheimer's Disease. Radiolabelled (Aoa-k)-RI-OR2-TAT was reproducibly synthesised and the product of the reaction with FPCA has been fully characterised. In-vivo biodistribution of [(18)F]RI-OR2-TAT has been measured in Wistar rats.

SUBMITTER: Morris O

PROVIDER: S-EPMC5034901 | biostudies-other | 2016 Oct

REPOSITORIES: biostudies-other

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Development & automation of a novel [(18)F]F prosthetic group, 2-[(18)F]-fluoro-3-pyridinecarboxaldehyde, and its application to an amino(oxy)-functionalised Aβ peptide.

Morris Olivia O Gregory J J Kadirvel M M Henderson Fiona F Blykers A A McMahon Adam A Taylor Mark M Allsop David D Allan Stuart S Grigg J J Boutin Herve H Prenant Christian C

Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine 20160727

2-[(18)F]-Fluoro-3-pyridinecarboxaldehyde ([(18)F]FPCA) is a novel, water-soluble prosthetic group. It's radiochemistry has been developed and fully-automated for application in chemoselective radiolabelling of amino(oxy)-derivatised RI-OR2-TAT peptide, (Aoa-k)-RI-OR2-TAT, using a GE TRACERlab FX-FN. RI-OR2-TAT is a brain-penetrant, retro-inverso peptide that binds to amyloid species associated with Alzheimer's Disease. Radiolabelled (Aoa-k)-RI-OR2-TAT was reproducibly synthesised and the produc ...[more]

PMID: 27518217

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Project description:IntroductionAmino acid based radiotracers target tumor cells through increased uptake by membrane-associated amino acid transport (AAT) systems. In the present study, four structurally related non-natural (18)F-labeled amino acids, (R)- and (S)-[(18)F]FAMP 1 and (R)- and (S)-[(18)F]MeFAMP 2 have been prepared and evaluated in vitro and in vivo for their potential utility in brain and systemic tumor imaging based upon primarily system A transport with positron emission tomography (PET).MethodsThe transport of enantiomers of [(18)F]FAMP 1 and [(18)F]MeFAMP 2 was measured through in vitro uptake assays in human derived cancer cells including A549 (lung), DU145 (prostate), SKOV3 (ovary), MDA MB468 (breast) and U87 (brain) in the presence and absence of amino acid transporter inhibitors. The in vivo biodistribution of these tracers was evaluated using tumor mice xenografts at 15, 30, 60 and 120 min post injection.ResultsAll four tracers showed moderate to high levels of uptake (1-9%ID/5×10(5) cells) by the cancer cell lines tested in vitro. AAT cell inhibition assays demonstrated that (R)-[(18)F]1 and (S)-[(18)F]1 entered these tumor cells via mixed AATs, likely but not limited to system A and system L. In contrast, (R)-[(18)F]2 and (S)-[(18)F]2 showed high selectivity for system A AAT. Similar to the results of in vitro cell studies, the tumor uptake of all four tracers was good to high and persisted over the 2 hours time course of in vivo studies. The accumulation of these tracers was higher in tumor than most normal tissues including blood, brain, muscle, bone, heart, and lung, and the tracers with the highest in vitro selectivity for system A AAT generally demonstrated the best tumor imaging properties. Higher uptake of these tracers was observed in the pancreas, kidney and spleen compared to tumors.ConclusionsThese preclinical studies demonstrate good imaging properties in a wide range of tumors for all four amino acids evaluated with (R)-[(18)F]2 having the highest selectivity for system A AAT.

Dataset Information

Development & automation of a novel [(18)F]F prosthetic group, 2-[(18)F]-fluoro-3-pyridinecarboxaldehyde, and its application to an amino(oxy)-functionalised A? peptide.

Publications

Development & automation of a novel [(18)F]F prosthetic group, 2-[(18)F]-fluoro-3-pyridinecarboxaldehyde, and its application to an amino(oxy)-functionalised Aβ peptide.

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