Synthesis, Preclinical Evaluation, and First-in-Human PET Study of Quinoline-Containing PSMA Tracers with Decreased Renal Excretion.
J Med Chem
; 64(7): 4179-4195, 2021 04 08.
Article
en En
| MEDLINE
| ID: mdl-33783213
ABSTRACT
The prostate-specific membrane antigen (PSMA) is considered to be an excellent theranostic target of prostate cancer (PCa). In this study, three 18F-labeled PSMA tracers with a more lipophilic quinoline functional spacer were designed, synthesized, and evaluated based on the Glu-Ureido-Lys binding motif. The effect of structure-related lipophilic difference on distribution and excretion of these tracers in vitro and in vivo (cells, rodent, primate, and human) was investigated by comparing with [18F]DCFPyL. There is no significant correlation between the renal elimination and the lipophilicity of the tracers in all species. However, the higher the lipophilicity of tracer, the higher the radioactivity accumulation in the liver of primate and human, and the less radioactivity is to excrete to the bladder with urine. The screened tracer [18F]8c, with a Ki value of 4.58 nM, displayed notable low bladder retention and demonstrated good imaging properties in patients with PCa.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Quinolinas
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Urea
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Medios de Contraste
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Radiofármacos
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Glutamato Carboxipeptidasa II
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Antígenos de Superficie
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China