Method for the synthesis of 18f-labelled biomolecules

1) A method for the synthesis of a compound of Formula I:

• or a salt or solvate thereof, wherein:
• R1-A- is a deprotonated radical of a biological targeting molecule (BTM) of formula R1-A-H wherein A is selected from S, O or NR2 wherein R2 is hydrogen, C1-6 alkyl, or C5-12 aryl;
• and,
• n is an integer of 1-6;
• wherein said method comprises:
• (i) providing [18F]Fluoride trapped on an ion-exchange cartridge;
• (ii) eluting the ion-exchange cartridge of step (i) with an aqueous solution comprising a first aliquot of an eluent, wherein said eluent comprises a cationic counterion in a suitable solvent, to obtain a [18F]Fluoride eluent;
• (iii) reacting a compound of Formula II:
• wherein LG1 and LG2 are the same or different and each represent a leaving group, and n is as defined for Formula I;
• in a first solvent with the [18F]Fluoride eluent obtained in step (ii) to obtain a compound of Formula III:
• wherein LG2 and n are as defined for Formula II;
• (iv) deprotonating a compound of Formula IV:
• or a protected version thereof, wherein A and R1 are as defined for Formula I;
• by addition of a second aliquot of the eluent as defined in step (ii);
• (v) reacting the compound of Formula III obtained in step (iii) with said deprotonated compound obtained in step (iv), or a protected version thereof, in a second solvent to obtain said compound of Formula I, or a protected version thereof, wherein said second solvent is an alkanol or an aqueous alkanol;
• (vi) removing any protecting groups.