Format:
14
ISSN:
1520-510X
Content:
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.
Note:
Im Text sind "nat/111", "nat/90", "nat/177" und jeweils "3+" hochgestellt, "6" tiefgestellt
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Gesehen am 17.05.2021
In:
Inorganic chemistry, Washington, DC : American Chemical Society, 1962, 59(2020), 10, Seite 7238-7251, 1520-510X
In:
volume:59
In:
year:2020
In:
number:10
In:
pages:7238-7251
In:
extent:14
Language:
English
DOI:
10.1021/acs.inorgchem.0c00671
URL:
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