title: Assessment of the best N(3-) donors in preparation of [M(N)(PNP)]-based (M=(99m)Tc-; (188)Re) 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 (HO2C-PEG600-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; 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 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 HO2C-PEG600-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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padua, Via Marzolo 5, 35131 Padova, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Carta
authors.affiliation: Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Jentschel
authors.affiliation: Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Thieme
authors.affiliation: Department of Pharmaceutical Sciences, University of Padua, Via Marzolo 5, 35131 Padova, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Salvarese
authors.affiliation: Department of Pharmaceutical Sciences, University of Padua, Via Marzolo 5, 35131 Padova, Italy.
authors.forename: Nicolò
authors.initials: N
authors.lastname: Morellato
authors.affiliation: IENI-CNR, Corso Stati Uniti 4, 35127 Padova, Italy.
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Refosco
authors.affiliation: ICB-CNR, Via Marzolo 1, 35131 Padova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ruzza
authors.affiliation: Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bergmann
authors.affiliation: Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany.
authors.forename: Hans-Jurgen
authors.initials: HJ
authors.lastname: Pietzsch
authors.affiliation: IENI-CNR, Corso Stati Uniti 4, 35127 Padova, Italy. Electronic address: bolzati@ieni.cnr.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bolzati
mesh_terms: D000818:Animals; D004355:Drug Stability; D006834:Hydrazines / Q000737:chemistry*; D008297:Male; D051379:Mice; D009584:Nitrogen / Q000737:chemistry*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011868:Radioisotopes; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D012211:Rhenium / Q000737:chemistry*; D013386:Succinates / Q000737:chemistry*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D006834:Hydrazines; D015609:Organotechnetium Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D013386:Succinates; C063357:succinic dihydrazide; D012211:Rhenium; D009584:Nitrogen
keywords: (188)Re; Diphosphinoamines; Peptide; Rhenium; Technetium; Therapy