La recherche menée dans notre laboratoire est notamment centrée sur la radiochimie et sur le développement de radiotraceurs qui pourront avoir des applications cliniques. Notre objectif est de découvrir ou de raffiner des outils en imagerie moléculaire, principalement par tomographie par émission de positons (TEP). La TEP constitue une option d’imagerie non invasive, quantitative et dynamique permettant d’observer des cibles biochimiques, comme des récepteurs ou des enzymes. Les produits radiopharmaceutiques utilisés en TEP peuvent duduedservir à étudier la biochimie des organismes vivants, à diagnostiquer une maladie ou aider à concevoir de nouveaux traitements.
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Publications
Voir la liste des publications actuelles sur PubMed.
Publications choisies :
- Farber, G; Boczar, KE; Wiefels, CC; Zelt, JGE; Guler, EC; deKemp, RA; Beanlands, RS; Rotstein, BH. “The future of cardiac molecular imaging.” Semin. Nucl. Med. 2020, 50, 367–385.
- Mair, BA; Fouad, MH; Ismailani, US; Munch, M; Rotstein, BH. “Rhodium-catalyzed addition of organozinc iodides to carbon11 isocyanates.” Org. Lett. 2020, 22, 2746–2750.
- Zelt, JGE; deKemp, RA; Rotstein, BH; Nair, GM; Narula, J; Ahmadi, A; Beanlands, RS; Mielniczuk, LM. “Nuclear imaging of the cardiac sympathetic nervous system: A disease specific interpretation in heart failure.” JACC Cardiovasc. Imaging. 2020, 13, 1036–1054.
- Al-Haddad, R; Ismailani, US; Rotstein, BH. “Current and future cardiovascular PET radiopharmaceuticals.” PET Clinics. 2019, 14, 293–305.
- Liang, SH; Wang, L; Stephenson, NA; Rotstein, BH; Vasdev, N. “Facile 18F-labeling of non-activated arenes via a spirocyclic iodonium(III) ylide method and its application in the synthesis of the mGluR5 PET radiopharmaceutical [18F]FPEB.” Nat. Protoc. 2019, 14, 1530–1545.
- Pekošak, A; Rotstein, BH; Collier, TL; Windhorst, AD; Vasdev, N; Poot, AJ. “Stereoselective ¹¹C-labeling of a "native" tetrapeptide using asymmetric phase-transfer catalyzed alkylation reactions.” Eur. J. Org. Chem. 2017, 1019–1024.
- Rotstein, BH; Liang, SH; Placzek, MS; Hooker, JM; Gee, AD; Dollé, F; Wilson, AA; Vasdev, N. “11C═O bonds made easily for positron emission tomography.” Chem. Soc. Rev. 2016, 45, 4708–4726.
- Rotstein, BH; Wang, L; Liu, RY; Patteson, J; Kwan, EE: Vasdev, N; Liang, SH. “Mechanistic studies and radiofluorination of structurally diverse pharmaceuticals with spirocyclic iodonium(III) ylides.” Chem. Sci. 2016, 7, 4407–4417.
- Rotstein, BH; Stephenson, NA; Vasdev, N; Liang, SL. “Spirocyclic hypervalent iodine(III)-mediated radiofluorination of non-activated and hindered aromatics.” Nature Commun. 2014, 5, 4365. doi: 10.1038/ncomms5365.
- Rotstein, BH; Wey, H-Y; Shoup, TM; Wilson, AA; Liang, SH; Hooker, JM; Vasdev, N. “PET imaging of fatty acid amide hydrolase with [18F]DOPP in non-human primates.” Mol. Pharmaceutics 2014, 11, 3832–3838.
Personnel
- Benjamin Rotstein
Professeur adjoint, chercheur
- Christina Bi
Undergraduate Student - Ariel Buchler
Graduate Student - Victoria Cao
Undergraduate Student - Gedaliah Farber
Graduate Student - Braeden Mair
Graduate Student - Maxime Munch
Postdoctoral Fellow - Kirabo Nekesa
Undergraduate Student - Uzair Sayani
Graduate Student
Intérêt principal
Radiochimie
Les isotopes principaux pour le radiomarquage des petites molécules des traceurs utilisés en TEP sont le carbone 11 et le fluor 18. En raison de leur courte période de radioactivité (20 et 110 minutes, respectivement), des réactions chimiques rapides et efficaces sont nécessaires pour les incorporer dans de petites molécules. Notre recherche en radiochimie est actuellement axée sur la préparation de nouveaux groupes fonctionnels avec le carbone 11, en ayant recours à des méthodes pratiques pour la préparation de produits radiopharmaceutiques.
Développement de radiotraceurs
Des sondes d’imagerie pour les cibles impliquées dans les maladies cardiovasculaires, les troubles neurologiques ou psychiatriques ou le cancer sont nécessaires pour mieux comprendre ces maladies, pour effectuer des diagnostics efficaces et pour développer des traitements. Notre laboratoire a recours à la chimie médicinale et à l’imagerie préclinique pour développer des radiotracteurs qui seront utiles aux chercheurs et praticiens d’Ottawa et de partout dans le monde.
Pour en savoir plus, veuillez consulter la page anglaise.
Projets
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. In order to take advantage of higher resolution and more easily quantifiable PET imaging, we are validating a fluorine-18 (18F, t1/2 = 109.7 min) radiotracer for imaging myocardial sympathetic innervation for human use. Translational studies are being conducted 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 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.
Offres d'emploi
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