Design, Synthesis, and Biological Evaluation of Novel Nonsteroidal 18F-Labeled PET Probes Specifically Targeting Estrogen Receptor α.
Mol Pharm
; 21(7): 3513-3524, 2024 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-38867453
ABSTRACT
The estrogen receptor α positive (ERα+) subtype represents nearly 70% of all breast cancers (BCs), which seriously threaten women's health. Positron emission computed tomography (PET) characterizes its superiority in detecting the recurrence and metastasis of BC. In this article, an array of novel PET probes ([18F]R-1, [18F]R-2, [18F]R-3, and [18F]R-4) targeting ERα based on the tetrahydropyridinyl indole scaffold were developed. Among them, [18F]R-3 and [18F]R-4 showed good target specificity toward ERα and could distinguish MCF-7 (ERα+) and MDA-MB-231 (ERα-) tumors efficiently. Especially, [18F]R-3 could differentiate the ERα positive/negative tumors successfully with a higher tumor-to-muscle uptake ratio (T/M) than that of [18F]R-4. The radioactivity of [18F]R-3 in the MCF-7 tumor was 5.24 ± 0.84%ID/mL and its T/M ratio was 2.49 ± 0.62 at 25 min postinjection, which might be the optimal imaging time point in PET scanning. On the contrary, [18F]R-3 did not accumulate in the MDA-MB-231 tumor at all. The autoradiography analysis of [18F]R-3 on the MCF-7 tumor-bearing mice model was consistent with the PET imaging results. [18F]R-3 exhibited the pharmacokinetic property of rapid distribution and slow clearance, making it suitable for use as a diagnostic PET probe. Overall, [18F]R-3 was capable of serving as a PET radiotracer to delineate the ERα+ tumor and was worthy of further exploitation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Radioisótopos de Flúor
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Compostos Radiofarmacêuticos
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Receptor alfa de Estrogênio
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Tomografia por Emissão de Pósitrons
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Mol Pharm
Assunto da revista:
BIOLOGIA MOLECULAR
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FARMACIA
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FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China