Improved Conjugation, 64-Cu Radiolabeling, in Vivo Stability, and Imaging Using Nonprotected Bifunctional Macrocyclic Ligands: Bis(Phosphinate) Cyclam (BPC) Chelators
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F18%3A10381894" target="_blank" >RIV/00216208:11310/18:10381894 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1021/acs.jmedchem.8b00932" target="_blank" >https://doi.org/10.1021/acs.jmedchem.8b00932</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.jmedchem.8b00932" target="_blank" >10.1021/acs.jmedchem.8b00932</a>
Alternative languages
Result language
angličtina
Original language name
Improved Conjugation, 64-Cu Radiolabeling, in Vivo Stability, and Imaging Using Nonprotected Bifunctional Macrocyclic Ligands: Bis(Phosphinate) Cyclam (BPC) Chelators
Original language description
Bifunctional derivatives of bis(phosphinate)bearing cyclam (BPC) chelators bearing a carboxylate, amine, isothiocyanate, azide, or cyclooctyne in the BP side chain were synthesized. Conjugations required no protection of phosphinate or ring secondary amine groups. The ring amines were not reactive (proton protected) at pH < similar to 8. For isothiocyanate coupling, oligopeptide N-terminal alpha-amines were more suitable than alkyl amines, e.g., Lys omega-amine (pK(a) similar to 7.5-8.5 and similar to 10-11, respectively) due to lower basicity. The Cu-64 labeling was efficient at room temperature (specific activity similar to 100 GBq/mu mol; 25 degrees C, pH 6.2, similar to 100 ligand equiv, 10 min). A representative Cu-64-BPC was tested in vivo showing fast clearance and no nonspecific radioactivity deposition. The monoclonal anti-PSCA antibody 7F5 conjugates with thiocyanate BPC derivative or NODAGA were radiolabeled and studied in PC3-PSCA tumor bearing mice by PET. The radiolabeled BPC conjugate was accumulated in the prostate tumor with a low off-target uptake, unlike Cu-64-labeled NODAGA-antibody conjugate. The BPC chelators have a great potential for theranostic applications of the Cu-64/Cu-67 matched pair.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - 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
Result continuities
Project
<a href="/en/project/GA17-13721S" target="_blank" >GA17-13721S: Copper isotopes and new theranostics</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Medicinal Chemistry
ISSN
0022-2623
e-ISSN
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Volume of the periodical
61
Issue of the periodical within the volume
19
Country of publishing house
US - UNITED STATES
Number of pages
23
Pages from-to
8774-8796
UT code for WoS article
000447470700018
EID of the result in the Scopus database
2-s2.0-85054098247