Synthesis and preclinical evaluation of 68Ga-labeled PSMA tracers with improved pharmacological properties.
Eur J Med Chem
; 274: 116545, 2024 Aug 05.
Article
em En
| MEDLINE
| ID: mdl-38823263
ABSTRACT
Prostate cancer (PCa) is one of the most common tumors in men, with the overexpression of prostate-specific membrane. In this study, we developed four new 68Ga-labeled PSMA-targeting tracers by introducing quinoline, phenylalanine and decanoic acid groups to enhance their lipophilicity, strategically limiting their metabolic pathway through the urinary system. Four radiotracers were synthesized with radiochemical purity >95 %, and exhibited high stability in vivo and in vitro. The inhibition constants (Ki) of SDTWS01-04 to PSMA were in the nanomolar range (<10 nM). Micro PET/CT imaging and biodistribution analysis revealed that 68Ga-SDTWS01 enabled clear tumor visualization in PET images at 1.5 h post-injection, with excellent pharmacokinetic properties. Notably, the kidney uptake of 68Ga-SDTWS01 significantly reduced, with higher tumor-to-kidney ratio (0.36 ± 0.02), tumor-to-muscle ratio (24.31 ± 2.10), compared with 68Ga-PSMA-11 (T/K 0.15 ± 0.01; T/M 14.97 ± 1.40), suggesting that 68Ga-SDTWS01 is a promising radiotracer for the diagnosis of PCa. Moreover, SDTWS01 with a chelator DOTA could also label 177Lu and 225Ac, which could be used for the treatment of PCa.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Glutamato Carboxipeptidase II
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
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Radioisótopos de Gálio
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China