Steven H. Liang, PhD, of the Department of Radiology, has received the 2017 Early Career Award in Chemistry of Drug Abuse and Addiction from the National Institute on Drug Abuse. The award is to facilitate basic chemistry research applied to drug abuse and addiction.
“My scientific interests are radiochemistry, nuclear medicine and positron emission tomography (PET) imaging – a key and fast-growing ground for translational science and precision medicine in patient care. I have developed several novel radiolabeling technologies and PET imaging biomarkers to access important biological targets that were previously inaccessible.
As the recipient of 2017 Early Career Award in Chemistry of Drug Abuse and Addiction (ECHEM award) from NIH, my team will develop and translate new PET biomarkers for imaging an important biological enzyme, monoacylglycerol lipase (MAGL) in the endocannabinoid system. MAGL inhibition has recently emerged as a therapeutic strategy to treat drug addiction, substance-use disorders as well as neurodegenerative diseases including Alzheimer’s disease. I am thankful to the NIH for this support which will help us develop an imaging tool which we hope can be progressed for translational human imaging studies and used to investigate underlying mechanisms of MAGL-linked diseases.”
One of our recently published articles on " [11C]Cyanation of arylboronic acids in aqueous solutions" has been selected by the Editorial Board of Synfactsfor its important insights. The highlight was published in Synfacts issue 08/2017. [PDF below] [original ariticle: see 2017 pub]
Metabotropic glutamate 2 receptors (mGlu2) are involved in the pathogenesis of several CNS disorders and neurodegenerative diseases. Pharmacological modulation of this target represents a potential disease-modifying approach for the treatment of substance abuse, depression, schizophrenia and dementias. While quantification of mGlu2 receptors in the living brain by positron emission tomography (PET) would help us better understand signaling pathways relevant to these conditions, few successful examples have been demonstrated to image mGlu2 in vivo...
Herein we report the first one-step synthesis of [18F]FDPA based on spirocyclic iodonium ylide (SCIDY) precursors from non-carried added [18F]fluoride. The ligand is synthesized in high yield (30% non-decay corrected at the end of synthesis)...
Positron emission tomography (PET) imaging study of fluorine-18 labeled biomolecules is an emerging and rapidly growing area for preclinical and clinical research. The present review focuses on recent advances in radiochemical methods for incorporating fluorine-18 into biomolecules via ‘direct’ or ‘indirect’ bioconjugation. Recently developed prosthetic...
Lorlatinib (PF-06463922) is a next-generation small molecule inhibitor of the orphan receptor tyrosine kinase c-ros oncogene 1 (ROS1), which has a kinase domain that is physiologically related to anaplastic lymphoma kinase (ALK), and is undergoing Phase I/II clinical trial investigations for treatment of non-small cell lung cancers. An early goal is to measure the concentrations of this drug in brain tumor lesions of lung cancer patients, and penetration of the blood-brain barrier is important...
In 2017, we have several SNMMI abstracts accepted as oral/poster presentations in Denver, Colorado this June. Dr. Longle Ma is selected to present his work in the RPSC Young Investigator Award Symposium. Dr. Dahl has two abstracts (poster and oral) to be presented in the recent advance of "in-loop" CO2 fixation. The list of abstracts is as follows:
[18F]Trifluoromethylthiolation of aliphatic electrophiles and α-bromo carbonyl compounds: A general and practical method for [18F]CF3S labeling from difluorocarbenes (Longle Ma)
Radiosynthesis of [11C]SL25.1188 via “in-Loop” [11C]CO2 Fixation: Pre-clinical Evaluation for MAO-B Activity in Alzheimer’s Disease (Kenneth Dahl)
Design and Prototype of an Automated "In-loop" [11C]CO2-Fixation Apparatus (Kenneth Dahl)
Nucleophilic Radiolabeling of Aryl-CF2H from [18F]Fluoride Ion (Gengyang Yuan)
Spirocyclic iodonium ylide-based radiolabeling of [18F]F-DPA and preliminary PET imaging studies (Lu Wang)
Novel 11C-labeled negative allosteric modulators for mGluR2 imaging (Xiaofei Zhang)
We will also host a 90 min education symposium (CE76) titled "Small Molecule and Bioconjugation PET Chemistry" with three speakers, Dr. Victor Pike (NIH), Dr. Magnus Schou (AZ and Karolinska) and Dr. Steven Liang (MGH/Harvard) to discuss the following topics. The symposium is sponsored by RPSC and scheduled on June 13 (Tuesday), 12:30-2:00 PM. Location: Mile High 3B (Colorado Convention Center)
learn the latest radiochemical methods for small molecule labelings
learn small molecule PET ligand development in both academia and industry
learn recent bioconjugation reactions with non-metallic PET radionuclides
Trifluoromethylthiolation by sulfuration of difluorocarbene with elemental sulfur is described for the first time, which overrides long-standing trifluoromethyl anion-based theory. Mechanistic elucidation reveals an unprecedented chemical process for the formation of thiocarbonyl fluoride and also enables transition-metal-mediated trifluoromethylthiolation and [18F]trifluoromethylthiolation of α-bromo carbonyl compounds with broad substrate scope and compatibility. [...
Iodonium compounds play a pivotal role in 18F-fluorination of radiopharmaceuticals containing non-activated arenes. However, preparation of these species is limited to oxidation conditions or exchange with organometallics that are prepared from aryl halides. Herein we describe a novel “one-pot” process to assemble aryl(isoquinoline)iodonium salts in 40–94 % yields from mesoionic carbene silver complex and Aryl-I-Py2(OTf)2....