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A Resin-linker-vector approach to radiopharmaceuticals containing 18F: application in the synthesis of O-(2-[18F]-Fluoroethyl)-L-tyrosine

A Resin-linker-vector approach to radiopharmaceuticals containing 18F: application in the synthesis of O-(2-[18F]-Fluoroethyl)-L-tyrosine
A Resin-linker-vector approach to radiopharmaceuticals containing 18F: application in the synthesis of O-(2-[18F]-Fluoroethyl)-L-tyrosine
A Resin-linker-vector (RLV) strategy is described for the radiosynthesis of tracer molecules containing the radionuclide 18F, which releases the labelled vector into solution upon nucleophilic substitution of a polystyrene-bound arylsulfonate linker with [18F]-fluoride ion. Three model linker-vector molecules 7?a–c containing different alkyl spacer groups were assembled in solution from (4-chlorosulfonylphenyl)alkanoate esters, exploiting a lipase-catalysed chemoselective carboxylic ester hydrolysis in the presence of the sulfonate ester as a key step. The linker-vector systems were attached to aminomethyl polystyrene resin through amide bond formation to give RLVs 8?a–c with acetate, butyrate and hexanoate spacers, which were characterised by using magic-angle spinning (MAS) NMR spectroscopy. On fluoridolysis, the RLVs 8?a,?b containing the longer spacers were shown to be more effective in the release of the fluorinated model vector (4-fluorobutyl)phenylcarbamic acid tert-butyl ester (9) in NMR kinetic studies and gave superior radiochemical yields (RCY?60?%) of the 18F-labelled vector. The approach was applied to the synthesis of the radiopharmaceutical O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]-FET), delivering protected [18F]-FET in >90?% RCY. Acid deprotection gave [18F]-FET in an overall RCY of 41?% from the RLV.
amino acids, positron-emission tomography, radiochemistry, radiopharmaceuticals, solid-phase synthesis
0947-6539
1720-1725
Topley, Amy C.
34b283a0-f281-4750-a204-3e189ec4c48b
Isoni, Valerio
0f2b13f4-5b30-4923-82b1-ccb3acb8a906
Logothetis, Thomas A.
9f42a28f-0c36-4d47-a137-7a317acb0237
Wynn, Duncan
fa315b3a-09f6-417b-8299-f9ab7435a494
Wadsworth, Harry
f337a299-e45d-45d6-936e-75c88492270f
Gibson, Alex M.R.
2fb435e0-5f7d-4dc2-b318-3fa7b65d4d74
Khan, Imtiaz
472f2db0-2192-4200-b2a7-9ac4cc798fd9
Wells, Neil J.
86312185-007b-495b-86da-4e2e5b9b8025
Perrio, Cécile
2155a2f3-6a4f-423a-aa40-07f56506f2df
Brown, Richard C.D.
21ce697a-7c3a-480e-919f-429a3d8550f5
Topley, Amy C.
34b283a0-f281-4750-a204-3e189ec4c48b
Isoni, Valerio
0f2b13f4-5b30-4923-82b1-ccb3acb8a906
Logothetis, Thomas A.
9f42a28f-0c36-4d47-a137-7a317acb0237
Wynn, Duncan
fa315b3a-09f6-417b-8299-f9ab7435a494
Wadsworth, Harry
f337a299-e45d-45d6-936e-75c88492270f
Gibson, Alex M.R.
2fb435e0-5f7d-4dc2-b318-3fa7b65d4d74
Khan, Imtiaz
472f2db0-2192-4200-b2a7-9ac4cc798fd9
Wells, Neil J.
86312185-007b-495b-86da-4e2e5b9b8025
Perrio, Cécile
2155a2f3-6a4f-423a-aa40-07f56506f2df
Brown, Richard C.D.
21ce697a-7c3a-480e-919f-429a3d8550f5

Topley, Amy C., Isoni, Valerio, Logothetis, Thomas A., Wynn, Duncan, Wadsworth, Harry, Gibson, Alex M.R., Khan, Imtiaz, Wells, Neil J., Perrio, Cécile and Brown, Richard C.D. (2013) A Resin-linker-vector approach to radiopharmaceuticals containing 18F: application in the synthesis of O-(2-[18F]-Fluoroethyl)-L-tyrosine. Chemistry - A European Journal, 19 (5), 1720-1725. (doi:10.1002/Chem.201202474). (PMID:23255371)

Record type: Article

Abstract

A Resin-linker-vector (RLV) strategy is described for the radiosynthesis of tracer molecules containing the radionuclide 18F, which releases the labelled vector into solution upon nucleophilic substitution of a polystyrene-bound arylsulfonate linker with [18F]-fluoride ion. Three model linker-vector molecules 7?a–c containing different alkyl spacer groups were assembled in solution from (4-chlorosulfonylphenyl)alkanoate esters, exploiting a lipase-catalysed chemoselective carboxylic ester hydrolysis in the presence of the sulfonate ester as a key step. The linker-vector systems were attached to aminomethyl polystyrene resin through amide bond formation to give RLVs 8?a–c with acetate, butyrate and hexanoate spacers, which were characterised by using magic-angle spinning (MAS) NMR spectroscopy. On fluoridolysis, the RLVs 8?a,?b containing the longer spacers were shown to be more effective in the release of the fluorinated model vector (4-fluorobutyl)phenylcarbamic acid tert-butyl ester (9) in NMR kinetic studies and gave superior radiochemical yields (RCY?60?%) of the 18F-labelled vector. The approach was applied to the synthesis of the radiopharmaceutical O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]-FET), delivering protected [18F]-FET in >90?% RCY. Acid deprotection gave [18F]-FET in an overall RCY of 41?% from the RLV.

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e-pub ahead of print date: 19 December 2012
Published date: 28 January 2013
Keywords: amino acids, positron-emission tomography, radiochemistry, radiopharmaceuticals, solid-phase synthesis
Organisations: Chemistry

Identifiers

Local EPrints ID: 356394
URI: http://eprints.soton.ac.uk/id/eprint/356394
ISSN: 0947-6539
PURE UUID: a303d88e-acc9-4f81-a426-5ac4f0639491
ORCID for Thomas A. Logothetis: ORCID iD orcid.org/0000-0002-3437-5287
ORCID for Neil J. Wells: ORCID iD orcid.org/0000-0002-4607-5791
ORCID for Richard C.D. Brown: ORCID iD orcid.org/0000-0003-0156-7087

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Date deposited: 25 Sep 2013 13:23
Last modified: 19 Nov 2019 01:56

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Contributors

Author: Amy C. Topley
Author: Valerio Isoni
Author: Duncan Wynn
Author: Harry Wadsworth
Author: Alex M.R. Gibson
Author: Imtiaz Khan
Author: Neil J. Wells ORCID iD
Author: Cécile Perrio

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