Development and biological evaluation of 68Ga-labeled peptides for potential application in HER2-positive colorectal cancer.
Bioorg Chem
; 151: 107645, 2024 Oct.
Article
em En
| MEDLINE
| ID: mdl-39059074
ABSTRACT
Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world. Human epidermal growth factor receptor 2 (HER2) is a promising target for the diagnosis and treatment of CRC. In this study, we aimed to design, synthesize and label peptide-based positron emission tomography (PET) tracers targeting HER2-positive CRC, namely [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02. The results show that [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02 possessed hydrophilicity, rapid pharmacokinetic properties and excellent stabilities. [68Ga]Ga-ES-02 demonstrated higher binding affinity (Kd = 24.29 ± 4.95 nM) toward the HER2 in CRC. In HER2-positive HT-29 CRC xenograft mouse model, PET study showed specific tumor uptake after injection of [68Ga]Ga-ES-02 (SUV15min max = 0.87 ± 0.03; SUV30min max = 0.64 ± 0.02). In biodistribution study, the T/M ratios of 68Ga-ES-02 at 30 min after injection reached a maximum of 4.07 ± 0.34. In summary, we successfully synthesized and evaluated two novel peptide-based PET tracers. Our data demonstrate that [68Ga]Ga-ES-01/02 is capable of HER2-positive colorectal cancer, with [68Ga]Ga-ES-02 showing superior imaging effect, enhanced targeting, and increased specificity.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Neoplasias Colorretais
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Receptor ErbB-2
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Tomografia por Emissão de Pósitrons
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Radioisótopos de Gálio
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Bioorg Chem
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Bioorganic chem
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Bioorganic chemistry
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos