Cyclam with a phosphinate-bis(phosphonate) pendant arm is a bone-targeting carrier of copper radionuclides

Result code in 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>

Alternative codes found

RIV/00216224:14310/22:00125995

Result on the web

<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>

Result language

angličtina

Original language name

Cyclam with a phosphinate-bis(phosphonate) pendant arm is a bone-targeting carrier of copper radionuclides

Original language description

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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10402 - Inorganic and nuclear chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Dalton Transactions

ISSN

1477-9226

e-ISSN

1477-9234

Volume of the periodical

51

Issue of the periodical within the volume

24

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

9541-9555

UT code for WoS article

000807023900001

EID of the result in the Scopus database

2-s2.0-85131966310