Structural requirements for stable binding of technetium-99m to derivatives of triglycine

To study the importance of the thiol function of mercaptoacetyltriglycine ( MAG3) for complexing technetium, we investigated a number of derivatives wh erein the thiol function of MAG3, is replaced by other metal binding groups such as 3-nitropropionyl, thiophene-2-carbonyl, pyrrole-2-carbonyl, acetoa cetyl, hydroxyacetyl, picolyl or aminoacetyl. These groups have the potenti al to form a bond with Tc via a free electron pair or the loss of a proton. 3-Nitropropionyltriglycine, thiophene-2-carbonyltriglycine and pyrrrole-2-c arbonyl triglycine were not able to form a single complex with Tc-99m. Unde r the experimental conditions, acetoacetyltriglycine forms a rather unstabl e Tc-99m-complex. On the other hand, the acetoacetyl group possesses suffic ient complexing capacity to serve as the fourth coordination site of a tetr aligand with a strongly technetium binding thiol and two amides. Hydroxyace tyltriglycine and derivatives of MAG3 in which the thiol group is substitut ed by an aromatic amine, as in picolyltriglycine, or an aliphatic amine, as in tetraglycine and other tetrapeptides, form complexes with technetium-99 m which are stable for several hours.