Succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG(600)-DTCZ) are nitrido nitrogen atom donors employed for the preparation of nitride [M(N)]-complexes (M = Tc-99m and Re-188). This study aims to compare the capability and the efficiency of these three N3- group donors, in the preparation of [M(N)PNP]-based target-specific compounds (M = Tc-99m, Re-188; PNP = aminodiphosphine). For this purpose, three different kit formulations (SDH kit; HO2C-PEG(600)-DTCZ kit; HDTCZ kit) were assembled and used in the preparation of [M(N)(cys similar to)(PNP3)](0/+) complexes (cys similar to = cysteine derivate ligands). For each formulation, the radiochemical yield (RCY) of the [M(N)(similar to cys)(PNP3)] compounds, was determined by HPLC. The deviation of the percentage of RCY, due to changes in concentration of the N3- donors and of the exchanging ligand, was determined. For Tc-99m, data clearly show that HDTCZ is the most efficient donor of N3-; however, SDH is the most suitable nitrido nitrogen atom donor for the preparation of [Tc-99m(N)(PNP)]-based target-specific agents with high specific activity. When HO2C-PEG(600)-DTCZ or HDTCZ are used in N3- donation, high amounts of the exchanging ligand (10(-4) M) were required for the formation of the final complex in acceptable yield. The possibility to use microgram amounts of HDTCZ also in [Re-188(N)] preparation (0.050 mg) reduces its ability to compete in ligand exchange reactions, minimizing the quantity of chelators required to obtain the final complex in high yield. This finding can be exploit for increasing the radiolabeling efficiency in [Re-188(N)]-radiopharmaceutical preparations compared to the previously reported HDTCZ-based procedure, notwithstanding a purification process could be necessary to improve the specific activity of the complexes. (C) 2014 Elsevier Inc. All rights reserved.