Molecular Imaging Probes and Radiochemistry Laboratory

Research in our lab includes basic science radiochemistry and translational radiotracer development. Our overall goal is discovery and refinement of tools for molecular imaging, principally by positron emission tomography (PET). PET allows for non-invasive, quantitative and dynamic imaging of biochemical targets, such as receptors or enzymes. A PET radiopharmaceutical can be used to study biochemistry in living systems, diagnose disease or help in development of therapeutics.

Focus 

Radiochemistry

The principal isotopes for radiolabeling small molecule PET tracers are carbon-11 and fluorine-18. Due to their short half-lives (20 and 110 minutes, respectively), rapid and efficient chemical reactions are needed to incorporate these into small molecules. Our radiochemistry research currently focuses on preparing new functional groups with carbon-11 by methods that will help us prepare radiopharmaceuticals.

Radiotracer Development

Imaging probes for targets implicated in cardiovascular disease, neurological and psychiatric disorders, and oncology are needed to better understand these conditions and develop effective diagnostics and treatments. Our lab uses medicinal chemistry and preclinical imaging to develop radiotracers that will be useful for researchers and practitioners in Ottawa and beyond.

Projects 

Novel Radiotracers for Inflammation in Atherosclerosis

Currently, it is difficult to detect and accurately predict plaque instability and rupture in atherosclerosis and it is therefore challenging to identify patients in need of treatment before a serious cardiovascular event. One of our goals is to develop a molecular-targeted imaging probe that will be useful for specifically identifying vulnerable plaque burden at high risk for rupture. This probe will allow us to quantitatively measure the density of enzymes that degrade the fibrous cap of atherosclerotic plaques and contribute to their destabilization and increase the likelihood of rupture and thrombus formation. In addition to diagnosis, the probe to be developed could be used to assist in development of therapies targeting these enzymes and to monitor patient response to treatment. This work is funded by the Canadian Institutes of Health Research (PJT148968).

Cardiac Innervation Imaging with PET

Quantitative, high resolution molecular imaging of the cardiac sympathetic nervous system would improve clinical management of associated diseases such as cardiac arrhythmias, congestive heart failure, ischemia, and some cardiac myopathies. Currently, two radiopharmaceuticals account for most cardiac sympathetic nerve imaging: meta-123I-iodobenzylguanidine (123I-MIBG) for planar and single-photon emission computed tomography (SPECT), and [11C]-meta-hydroxyephedrine ([11C]HED) for positron emission tomography (PET). In order to take advantage of higher resolution and more easily quantifiable PET imaging, as well as the simplified kinetics of benzylguanidines and improved accessibility over carbon-11 (t1/2 = 20.3 min) radiotracers, we will prepare and validate a fluorine-18 (18F, t1/2 = 109.7 min) radiotracer for imaging myocardial sympathetic innervation for human use. Translational studies are being conducted in rodent and porcine disease models to develop approaches for quantification of target density. Accompanied by acute toxicity and dosimetry data, these studies will pave the way for clinical evaluation in patients experiencing arrhythmias and HF. This work is supported by an ERLI grant from Heart & Stroke Foundation and its partners.

New Methods with Carbon-11

Carbon-11 (20.3 min half-life) is a versatile isotope for radiotracer development and preclinical imaging, due to its potential to radiolabel any organic compounds and nearly all biomolecules, drugs, and imaging agents. To synthesize imaging agents with carbon-11, chemical transformations need to be performed in rapid succession with high efficiency under strictly controlled conditions to ensure reproducible results and the safety and utility of products. Our research program develops improved chemical methods with carbon-11 and new imaging agents using this isotope. Specifically, we believe that methods for incorporating high oxidation state carbon-11 labels into molecules from its production form as carbon dioxide and similar derivatives such as carbon monoxide and cyanide will greatly expand the synthetic armament for this isotope and directly lead to novel and improved radiopharmaceuticals available to power molecular imaging. As part of this research, students will undergo a strong foundation of training in organic chemistry in addition to highly specialized training in radiochemistry with short-lived isotopes and radiopharmaceutical method development, ideally suited for future careers in the medicinal chemistry, radiopharmacy, and imaging sectors.

Publications 

See current publications list at PubMed.

Selected publications:

Staff 

Benjamin Rotstein
Assistant Professor, Scientist

Ariel Buchler
Undergraduate Co-Op
Email

Pasquale Linciano (starting May 2017)
Postdoctoral Fellow

Positions Available 

Opportunities

To enquire about available positions, please submit your CV with a cover letter detailing what you can bring to the team.

Contact:
brotstein@ottawaheart.ca 

 

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