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)

Succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO₂C-PEG₆₀₀-DTCZ) are nitrido nitrogen atom donors employed for the preparation of nitride [M(N)]‐complexes (M = ^99mTc and ¹⁸⁸Re).
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 = ^99mTc, ¹⁸⁸Re; PNP = aminodiphosphine). For this purpose, three different kit formulations (SDH kit; HO₂C-PEG₆₀₀-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 N³⁻ donors and of the
exchanging ligand, was determined.
For ^99mTc, 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 [^99mTc(N)(PNP)]-based target-specific agents with high specific activity. When HO₂C-PEG₆₀₀-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 usemicrogram amounts of HDTCZ also in [¹⁸⁸Re(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 [¹⁸⁸Re(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.