RGD Peptide-Conjugated Dodecaborate with the Ga-DOTA Complex: A Preliminary Study for the Development of Theranostic Agents for Boron Neutron Capture Therapy and Its Companion Diagnostics.
J Med Chem
; 65(24): 16741-16753, 2022 12 22.
Article
en En
| MEDLINE
| ID: mdl-36512639
ABSTRACT
A boron neutron capture therapy (BNCT) system, using boron-10-introduced agents coupled with companion diagnostics, is anticipated as a promising cancer theranostic. Thus, this study aimed to synthesize and evaluate a probe closo-dodecaborate-(Ga-DOTA)-c(RGDfK) (16) [Ga = gallium, DOTA =1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, and c(RGDfK) = cyclo(arginine-glycine-aspartate-d-phenylalanine-lysine] containing closo-dodecaborate ([B12H12]2-) as a boron cluster, a [67Ga]Ga-DOTA derivative for nuclear medicine imaging, and an RGD peptide for tumor targeting. Moreover, we prepared a radioiodinated probe [125I]17 in which I-125 is introduced into a closo-dodecaborate moiety of 16. [67Ga]16 and [125I]17 showed high stability and high uptake in cancer cells in vitro. Biodistribution experiments in tumor-bearing mice revealed similar biodistribution patterns between [67Ga]16 and [125I]17, such as a high uptake in the tumor and a low uptake in other non-target tissues. Meanwhile, [125I]17 exhibited higher accumulation in most tissues, including the tumor, than [67Ga]16, probably because of higher albumin binding. The higher the [125I]17 accumulation in the tumor, the more desirable it is for BNCT, with the possibility that the iodo-closo-dodecaborate site may work as an albumin binder.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Terapia por Captura de Neutrón de Boro
/
Neoplasias
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón