Synthesis, Preclinical Evaluation, and First-in-Human PET Study of [68Ga]-Labeled Biphenyl-Containing PSMA Tracers.
J Med Chem
; 66(18): 13332-13345, 2023 09 28.
Article
em En
| MEDLINE
| ID: mdl-37708404
ABSTRACT
Radioisotope-labeled prostate-specific membrane antigen (PSMA) PET tracers have gained popularity in diagnosing prostate cancer (PCa). This study aimed to improve the affinity and tumor-targeting capabilities of new PSMA tracers by increasing the number of pharmacophores that specifically bind to PSMA. Using biphenyl as a core scaffold, we investigated the relationship among spacer segments, affinity, and pharmacokinetic properties. In preclinical PET studies on mice with 22Rv1 tumors, compared with [68Ga]Ga-PSMA-11 (SUVmax = 3.37), [68Ga]Ga-PSMA-D5 (Ki = 0.15) showed higher tumor uptake (SUVmax = 3.51) and lower renal uptake (T/K = 1.84). In the first-in-human study, [68Ga]Ga-PSMA-D5 effectively detected small PCa-associated lesions and distant metastases. The advantages of [68Ga]Ga-PSMA-D5 include high tumor uptake, straightforward synthesis, and labeling, making it a promising PSMA PET tracer. Furthermore, [68Ga]Ga-PSMA-D5 contains a DOTA chelator, allowing convenient labeling with therapeutic radionuclides such as 177Lu and 225Ac, providing the potential for targeted radioligand therapy in PCa.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Radioisótopos de Gálio
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China