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1 Publication99mTc-Cyclopentadienyl Tricarbonyl Chelate-Labeled Compounds as Selective Sigma‑2 Receptor Ligands for Tumor Imaging
Li, D.; Chen, Y.; Wang, X.; Deuther-Conrad, W.; Chen, X.; Jia, B.; Dong, C.; Steinbach, J.; Brust, P.; Liu, B.; Jia, H.
Abstract
We have designed and synthesized a series of cyclopentadienyl tricarbonyl rhenium complexes containing a 5,6-dimethoxyisoindoline or a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline pharmacophore as σ2 receptor ligands. Rhenium compound 20a possessed low nanomolar σ2 receptor affinity (Ki = 2.97 nM) and moderate subtype selectivity (10-fold). Moreover, it showed high selectivity toward vesicular acetylcholine transporter (2374-fold), dopamine D2L receptor, NMDA receptor, opiate receptor, dopamine transporter, norepinephrine transporter, and serotonin transporter. Its corresponding radiotracer [99mTc]20b showed high uptake in a time- and dose-dependent manner in DU145 prostate cells and C6 glioma cells. In addition, this tracer exhibited high tumor uptake (5.92% ID/g at 240 min) and high tumor/blood and tumor/muscle ratios (21 and 16 at 240 min, respectively) as well as specific binding to σ receptors in nude mice bearing C6 glioma xenografts. Small animal SPECT/CT imaging of [99mTc]20b in the C6 glioma xenograft model demonstrated a clear visualization of the tumor at 180 min after injection.
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Journal of Medicinal Chemistry 59(2016)3, 934-946
DOI: 10.1021/acs.jmedchem.5b01378
Cited 18 times in Scopus
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