Organometallic Tc-99m-aquaion labels peptide to an unprecedented high specific activity

A new peptide labeling method that uses the organometallic aquaion [Tc-99m( H2O)(3)(CO)(3)](+) has been developed. Methods: A selection of amino acids was labeled at different concentrations with the organometallic aquaion, an d the labeling yield was determined by high-performance liquid chromatograp hy. This investigation has shown histidine to be a very potent ligand, with specific activities of up to 6 TBq/mu mol (160 Ci/mu mol) ligand. Histidin e derivatives have been coupled to neurotensin(8-13) (NT[8-13]) and have be en labeled with the aquaion, resulting in high specific activities with (N- alpha-histidinyl)acetic acid-NT(8-13) similar to those with histidine. Resu lts: Histidine derivatives of NT(8-13) labeled using this approach fully re tained their receptor affinity, showing K-D values of all investigated NT a nalogs below 1 nmol/L. on colon carcinoma HT29 cells. Biodistribution exper iments in BALB/c mice showed complete clearance of (N-alpha-histidinyl)acet ic acid-NT(8-13) from the blood after 24 h and no unwanted accumulation in any tissue. Conclusion: The novel labeling method using the organometallic Tc-99m-aquaion combines the advantage of highest specific activities with m inimal functionalization of proteins and peptides under retention of biolog ic affinity.