Improved Conjugation, 64-Cu Radiolabeling, in Vivo Stability, and Imaging Using Nonprotected Bifunctional Macrocyclic Ligands: Bis(Phosphinate) Cyclam (BPC) Chelators

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Improved Conjugation, 64-Cu Radiolabeling, in Vivo Stability, and Imaging Using Nonprotected Bifunctional Macrocyclic Ligands: Bis(Phosphinate) Cyclam (BPC) Chelators

Popis výsledku v původním jazyce

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 &lt; 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.

Název v anglickém jazyce

Improved Conjugation, 64-Cu Radiolabeling, in Vivo Stability, and Imaging Using Nonprotected Bifunctional Macrocyclic Ligands: Bis(Phosphinate) Cyclam (BPC) Chelators

Popis výsledku anglicky

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 &lt; 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10402 - Inorganic and nuclear chemistry

Projekt

<a href="/cs/project/GA17-13721S" target="_blank" >GA17-13721S: Izotopy mědi a nová teranostika</a><br>

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Journal of Medicinal Chemistry

ISSN

0022-2623

e-ISSN

—

Svazek periodika

61

Číslo periodika v rámci svazku

19

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

23

Strana od-do

8774-8796

Kód UT WoS článku

000447470700018

EID výsledku v databázi Scopus

2-s2.0-85054098247