Rapid thermodynamically stable complex formation of [nat/111In]In3+, [nat/90Y]Y3+, and [nat/177 Lu]Lu 3+ with H 6 dappa

• Verfasst von: Kostelnik, Thomas I. [VerfasserIn]
• Verfasst von: Wang, Xiaozhu [VerfasserIn]
• Verfasst von: Southcott, Lily [VerfasserIn]
• Verfasst von: Wagner, Hannah [VerfasserIn]
• Verfasst von: Kubeil, Manja [VerfasserIn]
• Verfasst von: Stephan, Holger [VerfasserIn]
• Verfasst von: Jaraquemada-Peláez, María de Guadalupe [VerfasserIn]
• Verfasst von: Orvig, Chris [VerfasserIn]
• Titel: Rapid thermodynamically stable complex formation of [nat/111In]In3+, [nat/90Y]Y3+, and [nat/177 Lu]Lu 3+ with H 6 dappa
• Verf.angabe: Thomas I. Kostelnik, Xiaozhu Wang, Lily Southcott, Hannah K. Wagner, Manja Kubeil, Holger Stephan, María de Guadalupe Jaraquemada-Peláez, and Chris Orvig
• E-Jahr: 2020
• Jahr: April 27, 2020
• Umfang: 14 S.
• Teil: volume:59
• Teil: year:2020
• Teil: number:10
• Teil: pages:7238-7251
• Teil: extent:14
• Fussnoten: Im Text sind "nat/111", "nat/90", "nat/177" und jeweils "3+" hochgestellt, "6" tiefgestellt ; Gesehen am 17.05.2021
• Titel Quelle: Enthalten in: Inorganic chemistry
• Ort Quelle: Washington, DC : American Chemical Society, 1962
• Jahr Quelle: 2020
• Band/Heft Quelle: 59(2020), 10, Seite 7238-7251
• ISSN Quelle: 1520-510X
• DOI: doi:10.1021/acs.inorgchem.0c00671
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1757907181

Abstract

A phosphinate-bearing picolinic acid-based chelating ligand (H6dappa) was synthesized and characterized to assess its potential as a bifunctional chelator (BFC) for inorganic radiopharmaceuticals. Nuclear magnetic resonance (NMR) spectroscopy was employed to investigate the chelator coordination chemistry with a variety of nonradioactive trivalent metal ions (In3+, Lu3+, Y3+, Sc3+, La3+, Bi3+). Density functional theory (DFT) calculations explored the coordination environments of aforementioned metal complexes. The thermodynamic stability of H6dappa with four metal ions (In3+, Lu3+, Y3+, Sc3+) was deeply investigated via potentiometric and spectrophotometric (UV-vis) titrations, employing a combination of acidic in-batch, joint potentiometric/spectrophotometric, and ligand-ligand competition titrations; high stability constants and pM values were calculated for all four metal complexes. Radiolabeling conditions for three clinically relevant radiometal ions were optimized ([111In]In3+, [177Lu]Lu3+, [90Y]Y3+), and the serum stability of [111In][In(dappa)]3- was studied. Through concentration-, time-, temperature-, and pH-dependent labeling experiments, it was determined that H6dappa radiolabels most effectively at near-physiological pH for all radiometal ions. Furthermore, very rapid radiolabeling at ambient temperature was observed, as maximal radiolabeling was achieved in less than 1 min. Molar activities of 29.8 GBq/μmol and 28.2 GBq/μmol were achieved for [111In]In3+ and [177Lu]Lu3+, respectively. For H6dappa, high thermodynamic stability did not correlate with kinetic inertness—lability was observed in serum stability studies, suggesting that its metal complexes might not be suitable as a BFC in radiopharmaceuticals.