Your browser doesn't support javascript.
loading
Tuning the Softness of the Pendant Arms and the Polyazamacrocyclic Backbone to Chelate the 203Pb/212Pb Theranostic Pair.
Tosato, Marianna; Randhawa, Parmissa; Lazzari, Luca; McNeil, Brooke L; Dalla Tiezza, Marco; Zanoni, Giordano; Mancin, Fabrizio; Orian, Laura; Ramogida, Caterina F; Di Marco, Valerio.
Afiliação
  • Tosato M; Department of Chemical Sciences, University of Padova, 35131 Padova, Italy.
  • Randhawa P; Radiopharmaceutical Chemistry Section, Nuclear Medicine Unit, AUSL-IRCCS Reggio Emilia, 42122 Reggio Emilia, Italy.
  • Lazzari L; Department of Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
  • McNeil BL; Life Sciences Division, TRIUMF, Vancouver, British Columbia V6T 2A3, Canada.
  • Dalla Tiezza M; Department of Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
  • Zanoni G; Life Sciences Division, TRIUMF, Vancouver, British Columbia V6T 2A3, Canada.
  • Mancin F; Department of Chemical Sciences, University of Padova, 35131 Padova, Italy.
  • Orian L; Department of Chemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
  • Ramogida CF; Life Sciences Division, TRIUMF, Vancouver, British Columbia V6T 2A3, Canada.
  • Di Marco V; Department of Chemical Sciences, University of Padova, 35131 Padova, Italy.
Inorg Chem ; 63(4): 1745-1758, 2024 Jan 29.
Article em En | MEDLINE | ID: mdl-38230993
ABSTRACT
A series of macrocyclic ligands were considered for the chelation of Pb2+ 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO4S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO3S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-10-acetamido-1,4,7,10-tetraazacyclododecane (DO3SAm), 1,7-bis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,10-diacetic acid (DO2A2S), 1,5,9-tris[2-(methylsulfanyl)ethyl]-1,5,9-triazacyclododecane (TACD3S), 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetrazacyclotridecane (TRI4S), and 1,4,8,11-tetrakis[2-(methylsulfanyl)ethyl]-1,4,8,11-tetrazacyclotetradecane (TE4S). The equilibrium, the acid-mediated dissociation kinetics, and the structural properties of the Pb2+ complexes formed by these chelators were examined by UV-Visible and nuclear magnetic resonance (NMR) spectroscopies, combined with potentiometry and density functional theory (DFT) calculations. The obtained results indicated that DO4S, DO3S, DO3SAm, and DO2A2S were able to efficiently chelate Pb2+ and that the most suitable macrocyclic scaffold for Pb2+ is 1,4,7,10-tetrazacyclododecane. NMR spectroscopy gave insights into the solution structures of the Pb2+ complexes, and 1H-207Pb interactions confirmed the involvement of S and/or O donors in the metal coordination sphere. Highly fluxional solution behavior was discovered when Pb2+ was coordinated to symmetric ligands (i.e., DO4S and DO2A2S) while the introduction of structural asymmetry in DO3S and DO3SAm slowed down the intramolecular dynamics. The ligand ability to chelate [203Pb]Pb2+ under highly dilute reaction conditions was explored through radiolabeling experiments. While DO4S and DO3S possessed modest performance, DO3SAm and DO2A2S demonstrated high complexation efficiency under mild reaction conditions (pH = 7, 5 min reaction time). The [203Pb]Pb2+ complexes' integrity in human serum over 24 h was appreciably good for [203Pb][Pb(DO4S)]2+ (80 ± 5%) and excellent for [203Pb][Pb(DO3SAm)]2+ (93 ± 1%) and [203Pb][Pb(DO2A2S)] (94 ± 1%). These results reveal the promise of DO2A2S and DO3SAm as chelators in cutting-edge theranostic [203/212Pb]Pb2+ radiopharmaceuticals.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ciclamos / Chumbo Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ciclamos / Chumbo Idioma: En Ano de publicação: 2024 Tipo de documento: Article