A Resin-Linker-Vector Approach to Radiopharmaceuticals Containing (18) F: Application in the Synthesis of O-(2-[(18) F]-Fluoroethyl)-L-tyrosine
Topley, AC; Isoni, V; Logothetis, TA; Wynn, D; Wadsworth, H; Gibson, AM; Khan, I; Wells, NJ; Perrio, C; Brown, RC
| HERO ID | 1454390 |
|---|---|
| In Press | No |
| Year | 2013 |
| Title | A Resin-Linker-Vector Approach to Radiopharmaceuticals Containing (18) F: Application in the Synthesis of O-(2-[(18) F]-Fluoroethyl)-L-tyrosine |
| Authors | Topley, AC; Isoni, V; Logothetis, TA; Wynn, D; Wadsworth, H; Gibson, AM; Khan, I; Wells, NJ; Perrio, C; Brown, RC |
| Journal | Chemistry: A European Journal |
| Volume | 19 |
| Issue | 5 |
| Page Numbers | 1720-1725 |
| Abstract | A Resin-linker-vector (RLV) strategy is described for the radiosynthesis of tracer molecules containing the radionuclide (18) F, which releases the labelled vector into solution upon nucleophilic substitution of a polystyrene-bound arylsulfonate linker with [(18) F]-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 (18) F-labelled vector. The approach was applied to the synthesis of the radiopharmaceutical O-(2-[(18) F]-fluoroethyl)-L-tyrosine ([(18) F]-FET), delivering protected [(18) F]-FET in >90 % RCY. Acid deprotection gave [(18) F]-FET in an overall RCY of 41 % from the RLV. |
| Doi | 10.1002/chem.201202474 |
| Pmid | 23255371 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |