Synthesis and Biological Evaluation of 99mTc-Labeled Phenylpiperazine Derivatives as Selective Serotonin-7 Receptor Ligands for Brain Tumor Imaging
| Autor: | Shahnaz Saednia, Seyed Mohammad Abedi, Saeed Emami, Seyed Jalal Hosseinimehr, Sajjad Molavipordanjani, Fereshteh Talebpour Amiri |
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| Rok vydání: | 2021 |
| Předmět: |
Biodistribution
medicine.drug_class Brain tumor Pharmaceutical Science Phenylpiperazine 02 engineering and technology Pharmacology 021001 nanoscience & nanotechnology Receptor antagonist medicine.disease 030226 pharmacology & pharmacy 5-HT7 receptor 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry Glioma Drug Discovery medicine Molecular Medicine Serotonin 0210 nano-technology Receptor |
| Zdroj: | Molecular Pharmaceutics. 18:2360-2374 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.1c00172 |
| Popis: | With a poor prognosis, glioblastoma multiforme is the most aggressive tumor of the central nervous system in humans. The aim of this study was to develop novel tracers for the tumor targeting and imaging of overexpressed serotonin-7 receptors (5-HT7Rs) in U-87 MG glioma xenografted nude mice. Two phenylpiperazine derivatives named as PHH and MPHH were designed, and the corresponding radiotracers 99mTc-PHH and 99mTc-MPHH were synthesized in high radiochemical purity (>95%). 99mTc-MPHH showed a higher affinity to 5-HT7Rs on U-87 MG cells compared to 99mTc-PHH. In biodistribution studies, the radiocomplexes showed good brain uptake at 15 min combined with good radioactivity retention in the brain for 240 min. Regional rabbit brain studies indicated a higher radioactivity concentration in the hippocampus and diencephalon than in the cerebellum. Compared to 99mTc-MPHH, the 99mTc-PHH exhibited a significantly increased tumor uptake at 15 and 60 min, but the rapid blood clearance of 99mTc-MPHH led to enhanced tumor-to-muscle ratios at 240 min. A significant reduction in tumor uptake 60 min after an injection of pimozide (5-HT7 receptor antagonist) confirms the tumor uptake was receptor-mediated specifically. The tumor-to-contralateral muscle tissue ratio of 99mTc-PHH and 99mTc-MPHH in nude mice with U-87 MG xenograft was measured (5.25 and 4.65) at 60 min as well as (6.25 and 6.76) at 240 min, respectively. |
| Databáze: | OpenAIRE |
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