A Structure-Activity Relationship Study of Bimodal BODIPY-Labeled PSMA-Targeting Bioconjugates.
ChemMedChem
; 16(16): 2535-2545, 2021 08 19.
Article
em En
| MEDLINE
| ID: mdl-33905162
ABSTRACT
The aim of this study was to identify a high-affinity BODIPY peptidomimetic that targets the prostate-specific membrane antigen (PSMA) as a potential bimodal imaging probe for prostate cancer. For the structure-activity study, several BODIPY (difluoroboron dipyrromethene) derivatives with varying spacers between the BODIPY dye and the PSMA Glu-CO-Lys binding motif were prepared. Corresponding affinities were determined by competitive binding assays in PSMA-positive LNCaP cells. One compound was identified with comparable affinity (IC50 =21.5±0.1 nM) to Glu-CO-Lys-Ahx-HBED-CC (PSMA-11) (IC50 =18.4±0.2 nM). Radiolabeling was achieved by Lewis-acid-mediated 19 F/18 F exchange in moderate molar activities (â¼0.7â
MBq nmol-1 ) and high radiochemical purities (>99 %) with mean radiochemical yields of 20-30 %. Cell internalization of the 18 F-labeled high-affinity conjugate was demonstrated in LNCaP cells showing gradual increasing PSMA-mediated internalization over time. By fluorescence microscopy, localization of the high-affinity BODIPY-PSMA conjugate was found in the cell membrane at early time points and also in subcellular compartments at later time points. In summary, a high-affinity BODIPY-PSMA conjugate has been identified as a suitable candidate for the development of PSMA-specific dual-imaging agents.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Compostos de Boro
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Glutamato Carboxipeptidase II
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Peptidomiméticos
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Antígenos de Superfície
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article