Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 58, Issue 14, Pages 5395-5407Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.5b00593
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [21471019]
- Deutsche Forschungsgemeinschaft Germany [STE 601/11-1]
- Helmholtz Association within Helmholtz Portfolio Topic Technologie und Medizin-Multimodale Bildgebung zur Aufklaerung des In-Vivo-Verhaltens von Polymeren Biomaterialien
- China Scholarship Council (CSC)
Ask authors/readers for more resources
We report the syntheses and evaluation of series of novel piperidine compounds with low lipophilicity as sigma(1) receptor ligarids. 8-(-4(2-Fluoroethoxy)benzyl)-1,4-dioxa-8,azaspiro [4.5]decane (5a) possessed high affinity (K-i = 5.4 +/- 0.4 nM) for sigma(1) receptors and selectivity for sigma(2) receptors (30-fold) and the vesicular acetylcholine transporter (1404-fold). [F-18]5a was prepared using a one-pot, two-step labeling procedure in an automated synthesis module, with a radiochemical purity of >95%, and a specific activity of 25-45 GBq/mu mol. Cellular association, biodistribution, and autoradiography with blocking experiments indicated specific binding of [F-18]5a to sigma(1) receptors in vitro and in vivo. Small annual positron emission tomography (PET) imaging using mouse tumor xenograft models demonstrated a high accumulation in human carcinoma and melanoma. Treatment with haloperidol significantly reduced the accumulation of the radiotracer in tumors. These findings suggest that radiotracer with suitable lipophilicity and appropriate affinity for sigma(1) receptors could be used for tumor imaging.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available