Validation of a post-radiolabeling bioconjugation strategy for radioactive rare earth complexes with minimal structural footprint.
Chem Commun (Camb)
; 58(99): 13728-13730, 2022 Dec 13.
Article
em En
| MEDLINE
| ID: mdl-36426996
ABSTRACT
The nine-coordinate aza-macrocycle DO3Apic-NO2 and its kinetically inert rare earth complexes [M(DO3A-pic-NO2)]- (M = La, Tb, Eu, Lu, Y) can be readily bioconjugated to surface accessible thioles on peptides and proteins with a minimal structural footprint. All complexes express thioconjugation rate constants in the same order of magnitude (k = 0.3 h-1) with the exception of Sc (k = 0.89 h-1). Coupling to peptides and biologics with accessible cysteines also enables post-radiochelation bioconjugation at room temperature to afford injection-ready radiopharmaceuticals as demonstrated by formation of [177Lu][Lu(DO3Apic-NO2)]- and [86Y][Y(DO3Apic-NO2)]-, followed by post-labeling conjugation to a cysteine-functionalized peptide targeting the prostate specific membrane antigen. The 86Y-labeled construct efficiently localizes in target tumors with no significant off-target accumulation as evidenced by positron emission tomography, biodistribution studies and metabolite analysis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Radiofarmacêuticos
/
Metais Terras Raras
Limite:
Humans
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Male
Idioma:
En
Revista:
Chem Commun (Camb)
Ano de publicação:
2022
Tipo de documento:
Article