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Synthesis and Biological Evaluation of 99m Tc-Labeled Phenylpiperazine Derivatives as Selective Serotonin-7 Receptor Ligands for Brain Tumor Imaging
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-HT Rs) in U-87 MG glioma xenografted nude mice. Two ph...
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Published in: | Molecular pharmaceutics 2021-06, Vol.18 (6), p.2360-2374 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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-HT
Rs) in U-87 MG glioma xenografted nude mice. Two phenylpiperazine derivatives named as
and
were designed, and the corresponding radiotracers
Tc-
and
Tc-
were synthesized in high radiochemical purity (>95%).
Tc-
showed a higher affinity to 5-HT
Rs on U-87 MG cells compared to
Tc-
. 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
Tc-
, the
Tc-
exhibited a significantly increased tumor uptake at 15 and 60 min, but the rapid blood clearance of
Tc-
led to enhanced tumor-to-muscle ratios at 240 min. A significant reduction in tumor uptake 60 min after an injection of pimozide (5-HT
receptor antagonist) confirms the tumor uptake was receptor-mediated specifically. The tumor-to-contralateral muscle tissue ratio of
Tc-
and
Tc-
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. |
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ISSN: | 1543-8384 1543-8392 |
DOI: | 10.1021/acs.molpharmaceut.1c00172 |