Cyclam with a phosphinate-bis(phosphonate) pendant arm is a bone-targeting carrier of copper radionuclides
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F22%3A10444999" target="_blank" >RIV/00216208:11310/22:10444999 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00216224:14310/22:00125995
Výsledek na webu
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=7xSrPP4koH" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=7xSrPP4koH</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/d2dt01172g" target="_blank" >10.1039/d2dt01172g</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Cyclam with a phosphinate-bis(phosphonate) pendant arm is a bone-targeting carrier of copper radionuclides
Popis výsledku v původním jazyce
Ligands combining a bis(phosphonate) group with a macrocycle function as metal isotope carriers for radionuclide-based imaging and for treating bone metastases associated with several cancers. However, bis(phosphonate) pendant arms often slow down complex formation and decrease radiochemical yields. Nevertheless, their negative effect on complexation rates may be mitigated by using a suitable spacer between bis(phosphonate) and the macrocycle. To demonstrate the potential of bis(phosphonate) bearing macrocyclic ligands as a copper radioisotope carrier, we report the synthesis of a new cyclam derivative bearing a phosphinate-bis(phosphonate) pendant (H5te1P(BP)). The ligand showed a high selectivity to Cu(II) over Zn(II) and Ni(II) ions, and the bis(phosphonate) group was not coordinated in the Cu(II) complex, strongly interacting with other metal ions in solution. The Cu(II) complex formed quickly, in 1 s, at pH 5 and at a millimolar scale. The complexation rates significantly differed under a ligand or metal ion excess due to the formation of reaction intermediates differing in their metal-to-ligand ratio and protonation state, respectively. The Cu(II)-te1P(BP) complex also showed a high resistance to acid-assisted hydrolysis (t(1/2) 2.7 h; 1 M HClO4, 25 °C) and was effectively adsorbed on the hydroxyapatite surface. H5te1P(BP) radiolabeling with [(64)Cu]CuCl2 was fast and efficient, with specific activities of approximately 30 GBq (64)Cu per 1 μmol of ligand (pH 5.5, room temperature, 30 min). In a pilot experiment, we further demonstrated the excellent suitability of [(64)Cu]Cu(II)-te1P(BP) for imaging active bone compartments by dedicated small animal PET/CT in healthy mice and subsequently in a rat femoral defect model, in direct comparison with [(18)F]fluoride. Moreover, [(64)Cu]Cu(II)-te1P(BP) showed a higher uptake in critical bone defect regions. Therefore, our study highlights the potential of [(64)Cu]Cu(II)-te1P(BP) as a PET radiotracer for evaluating bone healing in preclinical and clinical settings with a diagnostic value similar to that of [(18)F]fluoride, albeit with a longer half-life (12.7 h) than (18)F (1.8 h), thereby enabling extended observation times.
Název v anglickém jazyce
Cyclam with a phosphinate-bis(phosphonate) pendant arm is a bone-targeting carrier of copper radionuclides
Popis výsledku anglicky
Ligands combining a bis(phosphonate) group with a macrocycle function as metal isotope carriers for radionuclide-based imaging and for treating bone metastases associated with several cancers. However, bis(phosphonate) pendant arms often slow down complex formation and decrease radiochemical yields. Nevertheless, their negative effect on complexation rates may be mitigated by using a suitable spacer between bis(phosphonate) and the macrocycle. To demonstrate the potential of bis(phosphonate) bearing macrocyclic ligands as a copper radioisotope carrier, we report the synthesis of a new cyclam derivative bearing a phosphinate-bis(phosphonate) pendant (H5te1P(BP)). The ligand showed a high selectivity to Cu(II) over Zn(II) and Ni(II) ions, and the bis(phosphonate) group was not coordinated in the Cu(II) complex, strongly interacting with other metal ions in solution. The Cu(II) complex formed quickly, in 1 s, at pH 5 and at a millimolar scale. The complexation rates significantly differed under a ligand or metal ion excess due to the formation of reaction intermediates differing in their metal-to-ligand ratio and protonation state, respectively. The Cu(II)-te1P(BP) complex also showed a high resistance to acid-assisted hydrolysis (t(1/2) 2.7 h; 1 M HClO4, 25 °C) and was effectively adsorbed on the hydroxyapatite surface. H5te1P(BP) radiolabeling with [(64)Cu]CuCl2 was fast and efficient, with specific activities of approximately 30 GBq (64)Cu per 1 μmol of ligand (pH 5.5, room temperature, 30 min). In a pilot experiment, we further demonstrated the excellent suitability of [(64)Cu]Cu(II)-te1P(BP) for imaging active bone compartments by dedicated small animal PET/CT in healthy mice and subsequently in a rat femoral defect model, in direct comparison with [(18)F]fluoride. Moreover, [(64)Cu]Cu(II)-te1P(BP) showed a higher uptake in critical bone defect regions. Therefore, our study highlights the potential of [(64)Cu]Cu(II)-te1P(BP) as a PET radiotracer for evaluating bone healing in preclinical and clinical settings with a diagnostic value similar to that of [(18)F]fluoride, albeit with a longer half-life (12.7 h) than (18)F (1.8 h), thereby enabling extended observation times.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10402 - Inorganic and nuclear chemistry
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2022
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Dalton Transactions
ISSN
1477-9226
e-ISSN
1477-9234
Svazek periodika
51
Číslo periodika v rámci svazku
24
Stát vydavatele periodika
GB - Spojené království Velké Británie a Severního Irska
Počet stran výsledku
15
Strana od-do
9541-9555
Kód UT WoS článku
000807023900001
EID výsledku v databázi Scopus
2-s2.0-85131966310