Modular Synthesis of Peptide-Based Single- and Multimodal Targeted Molecular Imaging Agents.
ACS Appl Bio Mater
; 4(7): 5435-5448, 2021 07 19.
Article
em En
| MEDLINE
| ID: mdl-35006725
ABSTRACT
A practical, modular synthesis of targeted molecular imaging agents (TMIAs) containing near-infrared dyes for optical molecular imaging (OMI) or chelated metals for magnetic resonance imaging (MRI) and single-photon emission correlation tomography (SPECT) or positron emission tomography (PET) has been developed. In the method, imaging modules are formed early in the synthesis by attaching imaging agents to the side chain of protected lysines. These modules may be assembled to provide a given set of single- or dual-modal imaging agents, which may be conjugated in the last steps of the synthesis under mild conditions to linkers and targeting groups. A key discovery was the ability of a metal such as gadolinium, useful in MRI, to serve as a protecting group for the chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). It was further discovered that two lanthanide metals, La and Ce, can double as protecting groups and placeholder metals, which may be transmetalated under mild conditions by metals used for PET in the final step. The modular method enabled the synthesis of discrete targeted probes with two of the same or different dyes, two same or different metals, or mixtures of dyes and metals. The approach was exemplified by the synthesis of single- or dual-modal imaging modules for MRI-OMI, PET-OMI, and PET-MRI, followed by conjugation to the integrin-seeking peptide, c(RGDyK). For Gd modules, their efficacy for MRI was verified by measuring the NMR spin-lattice relaxivity. To validate functional imaging of TMIAs, dual-modal agents containing Cy5.5 were shown to target A549 cancer cells by confocal fluorescence microscopy.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tomografia Computadorizada por Raios X
/
Gadolínio
Idioma:
En
Revista:
ACS Appl Bio Mater
Ano de publicação:
2021
Tipo de documento:
Article