Assessment of the best N3 − donors in preparation of [M(N)(PNP)]-based (M = 99mTc-; 188Re) target-specific radiopharmaceuticals: Comparison among succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ)

Abstract Succinic dihydrazide (SDH), N -methyl- S -methyl dithiocarbazate (HDTCZ) and PEGylated N -methyl- S -methyl dithiocarbazate (HO 2 C-PEG 600 -DTCZ) are nitrido nitrogen atom donors employed for the preparation of nitride [M(N)]‐complexes (M= 99m Tc and 188 Re). This study aims to compare the capability and the efficiency of these three N 3− group donors, in the preparation of [M(N)PNP]-based target-specific compounds (M= 99m Tc, 188 Re; PNP=aminodiphosphine). For this purpose, three different kit formulations (SDH kit; HO 2 C-PEG 600 -DTCZ kit; HDTCZ kit) were assembled and used in the preparation of [M(N)(cys~)(PNP3)] 0/+ complexes (cys~=cysteine derivate ligands). For each formulation, the radiochemical yield (RCY) of the [M(N)(~cys)(PNP3)] compounds, was determined by HPLC. The deviation of the percentage of RCY, due to changes in concentration of the N 3− donors and of the exchanging ligand, was determined. For 99m Tc, data clearly show that HDTCZ is the most efficient donor of N 3− ; however, SDH is the most suitable nitrido nitrogen atom donor for the preparation of [ 99m Tc(N)(PNP)]-based target-specific agents with high specific activity. When HO 2 C-PEG 600 -DTCZ or HDTCZ are used in N 3− 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 [ 188 Re(N)] preparation (0.050mg) 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 [ 188 Re(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.