Radioconjugation method

A method for radiolabelling a biological targeting molecule which comprises:

• (i) providing a compound of Formula (IA)
• [BTM]-X1 (IA);
• (ii) deprotection of the compound of Formula (IA) of step (i) to give an aminooxy compound of Formula (IIA)
• [BTM]-O—NH2 (IIA);
• (iii) condensation of the aminooxy compound of Formula (IIA) with a carbonyl compound of Formula (IIIA)
• Q-[linker]-(C═O)Y1 (IIIA);
• to give a radiolabelled conjugate of Formula (IVA)
• [BTM]-O—N═(CY1)-[linker]-Q (IVA);
• wherein:
• [BTM] is a biological targeting molecule, which after administration, localizes at a site of a mammalian body, with the proviso that when the [BTM] is a peptide that has a carboxyl and an amine terminus, it has a metabolism inhibiting group (MIG) conjugated on one or both of said termini, wherein, for the amine terminus, the MIG is selected from NH(C═O)RG, wherein RG is selected from C1-C6 alkyl, C3-C10 aryl or comprises polyethylene glycol, and for the carboxyl terminus, the MIG is selected from carboxamide, tert-butyl ester, benzyl ester, cyclohexyl ester, amino alcohol, and polyethylene glycol;
• X1 is a protected aminooxy group of formula:
• wherein R1 and R2 are independently selected from C1-3 alkyl, C1-3 fluoroalkyl or C4-6 aryl;
• Q is a PET or SPECT radioisotope for imaging in vivo, wherein said radioisotope is selected from the group consisting of 18F, 123I, 99mTc, 68Ga and 64Cu;
• Y1 is H, C1-6 alkyl or C4-10 aryl;
• and
• [linker] is a linker group of formula -(A)m wherein each A is independently —CR2—, CR═CR—, —C≡C—, —CR2CO2—, —CO2CR2—, —NRCO—, —CONR—, —NR(C═O)NR—, —NR(C═S)NR—, —SO2NR—, —NRSO2—, —CR2OCR2—, —CR2SCR2—, —CR2NRCR2—, a C4-8 cycloheteroalkylene group, a C4-8 cycloalkylene group, a C5-12 arylene group, or a C3-12 heteroarylene group, wherein each R is independently selected from:
• H, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkoxyalkyl or C1-4 hydroxyalkyl, and m is an integer of value 1 to 20.