Add time:07/22/2019         Source:sciencedirect.com

[(Methyl-pyridin-2-ylmethyl-amino)-methyl]-phosphonic acid is a new bifunctional chelator for the fac-[99mTc(CO3)]+ core which can be linked to biomolecules via formation of phosphonic acid esters. Its synthesis and the coupling to model alcohols and to a bioactive molecule (cobinamide) are described. The rhenium complexes [Re(CO)3L] of the esters have been prepared and characterized, one of them by X-ray crystallography. The model esters could be labeled with [99mTc(OH2)3(CO)3]+ under mild conditions and relatively low ligand concentration with >97% yield and only one isomer formed. The 99mTc-labeled cobinamide analog was a mixture of four isomers. It bound strongly to transcobalamin I (TC I, haptocorrin) but only slightly to transcobalamin II (TC II) and intrinsic factor (IF), reflecting the binding abilities of cobinamide. Biodistribution studies in mice with B16 melanoma exhibited fast clearance with no specific tissue binding.

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