TC-99M-LABELING KINETICS OF 4 THIOL-CONTAINING CHELATORS AND 2-HYDRAZINOPYRIDINE - FACTORS INFLUENCING THEIR RADIOLABELING EFFICIENCY

The relative Tc-99m-labeling efficiency of several potentially tetrade ntate thiol-containing chelators was studied by competing them with gl ucoheptonate in the [Tc-99m]glucoheptonate complex, and was compared t o that of 2-hydrazinopyridine (HYPY), a model compound for HYNIC (hydr azinonicotinamide). The thiol-containing chelators in their unprotecte d forms include 4,5-bis(mercaptoacetamido)pentanoic acid (H(4)L1), N-[ 2-(mercapto)propionyl]glycylglycylglycine (H(4)L2), 2-(mercapto)ethyla minoacetyl-L-cysteine (H(3)L3), and N,N'-ethylenediyl-bis-L-cysteine d iethyl ester (H(3)L4). There are several factors that influence the la beling efficiency of a chelator. These include donor atoms, chelator c oncentration, and reaction conditions such as temperature and reaction time, and pH of the reaction media. In all the cases, higher chelator concentration produces better radiolabeling yields. Heating at 100 de grees C for 30 min is required for the successful Tc-99m-labeling of N 2S2 diamidedithol (H(4)L1) and N3S triamidethiol (H(4)L2), while the N 2S2 monoamide monoaminedithiol (H(3)L3) can be well labeled under mild er conditions. For the N2S2 diaminedithiol (H(3)L4), the ligand exchan ge could be completed within 60 min at room temperature. It is clear t hat substitution of an amine-N for an amide-N enhances the rate of Tc- 99m - labeling. The reaction of HYPY with [Tc-99m]glucoheptonate was c arried out by heating the reaction mixture at 50 degrees C for 30 min under acidic conditions (pH 4-5). The radiolabeling efficiency of HYPY using glucoheptonate as coligand is better than that of H(4)L1-H(3)L3 , and is comparable to that of H3L4. Therefore, HYNIC and diaminedithi ols are the candidates of choice as bifunctional coupling agents in la beling small biologically active molecules with very high potency. (C) 1997 The Du Pont Merck Pharmaceutical Company Published by Elsevier S cience Ltd.