Abstract
Both 1-azabicyclo[2.2.2]oct-3-yl α-(1-fluoroeth-2-yl)-α-hydroxy-α-phenylacetate (FQNE, 5) and 1-azabicyclo[2.2.2]oct-3-yl α-(1-fluoropent-5-yl)-α-hydroxy-α-phenylacetate (FQNPe, 6) were prepared and evaluated as potential candidates for the determination of muscarinic cholinergic receptor (mAChR) density by positron emission tomography (PET). The results of in vitro binding assays demonstrated that although both 5 and 6 had high binding affinities for m1 and m2 mAChR subtypes, 6 displayed a higher affinity (nM, m1; KD, 0.45, m2; KD, 3.53) as compared to 5 (nM, m1; KD, 12.5, m2; KD, 62.8). It was observed that pretreatment of female Fisher rats with either 5 or 6 prior to the i.v. administration of Z-(-)(-)-[131I]-IQNP, a high-affinity muscarinic ligand, significantly blocked the uptake of radioactivity in the brain and heart measured 3 h postinjection of the radiolabeled ligand. These new fluoro QNB analogues represent important target ligands for evaluation as potential receptor imaging agents in conjunction with PET. NUCL MED BIOL 23;3:267-276, 1996.
Original language | English |
---|---|
Pages (from-to) | 267-276 |
Number of pages | 10 |
Journal | Nuclear Medicine and Biology |
Volume | 23 |
Issue number | 3 |
DOIs | |
State | Published - Apr 1996 |
Funding
Research was supported at Oak Ridge National Laboratory by the Office of Health and Environmental Research (OHER), U.S. Department of Energy (DOE), under contract DE-AC05-960R22464 with Lock-heed Martin Energy Research Corporation, and at the George Washington University Medical Center by NIH grant NS-22215 and DOE grant DE FG0588ER60649. The authors thank Dr. J. Baumgold for providing the transfected cell membranes, Ms. Carla R. Lambert for assisting with the tissue distribution studies, and Ms. S. Milligan for typing the manuscript. Huimin Luo, PhD, gratefully acknowledges support from the Alexander Hollaender Distinguished Postdoctoral Fellowship Program sponsored by the U.S. Department of Energy, Office of Health and Environmental Research, and administered by the Oak Ridge Institute for Science and Education.
Funders | Funder number |
---|---|
OHER | |
Office of Health and Environmental Research | |
National Institutes of Health | DE FG0588ER60649 |
U.S. Department of Energy | DE-AC05-960R22464 |
National Institute of Neurological Disorders and Stroke | R01NS022215 |
Oak Ridge National Laboratory | |
Oak Ridge Institute for Science and Education |
Keywords
- Fluorine-18
- Fluoroalkyl group
- Muscarinic receptor
- PET
- QNB analogues