Biography
Dr. Rotstein received his Ph.D. from the University of Toronto working with Prof. Andrei Yudin on peptide macrocyclization technologies. As an NSERC Postdoctoral Fellow and Instructor at Harvard Medical School and Massachusetts General Hospital, he developed radiochemical methodologies and contributed to translational positron emission tomography radiotracer development for several neuroimaging targets related to psychiatry and dementia. Dr. Rotstein leads the Molecular Imaging Probes and Radiochemistry Laboratory at University of Ottawa Heart Institute where his research focuses on novel radiochemical methods to accelerate tracer discovery and cardiovascular nuclear imaging. He teaches courses in Chemistry and the Translational and Molecular Medicine program, including practical training with the Preclinical Imaging Core.
Research Interests
Molecular imaging of dynamic biochemical processes is used to study normal and diseased conditions, evaluate response to therapy, and for clinical diagnosis. Radiotracers for positron emission tomography (PET) contain short-lived isotopes and engage in highly specific interactions with enzyme or receptor targets in vivo. Radiotracer development therefore demands a confluence of understanding of biochemical processes and targets, medicinal chemistry and probe design, synthetic and radiochemistry, as well as pharmacology and image analysis. From a foundation in all aspects of radiopharmaceutical chemistry, our laboratory seeks to develop strategies and methods for applications ultimately in molecular imaging and clinical diagnosis.
Specific research goals we are pursuing include:
- Efficient and practical methods for incorporation of radioisotopes into small molecules and conjugation to biomolecules, with an emphasis on carbon-11 and fluorine-18;
- Targeted and selective imaging probes for biochemical processes related to cardiology, neuroscience, and/or oncology preclinical and translational research;
- Imaging validation of biomarkers for precision profiling of disease, drug development, and monitoring response to therapeutic intervention.
Our labs are based at the University of Ottawa Heart Institute to leverage a full complement of radiopharmaceutical and nuclear imaging infrastructure. Research in our labs is cross-disciplinary, collaborative and seeks translation of basic science discovery to clinical relevance. We eagerly collaborate across domains to facilitate access to preclinical nuclear imaging tools and support our initiatives.
Selected Publications
Mair, BA; Zelt, JGE; Nekesa, K; Saint-Georges, Z; Dinelle, K; Adi, M; Robinson, S; Mielniczuk, LM; Shlik, J; Beanlands, RS; deKemp, RA; Rotstein, BH. “Pharmacological and metabolic parameters of [18F]flubrobenguane in clinical imaging populations.” J. Nucl. Cardiol. 2023, 30, 2089–2095.
Buchler, A; Ismailani, US; MacMullin, N; Abdirahman, F; Adi, M; Bi, C; Jany, C; Keillor, JW; Rotstein, BH. “Quinazoline-2-carboxamides as selective PET radiotracers for matrix metalloproteinase-13 imaging in atherosclerosis.” J. Med. Chem. 2023, 66, 6682–6696.
Ismailani, US; Buchler, A; MacMullin, N; Abdirahman, F; Adi, M; Rotstein, BH. “Synthesis and evaluation of [11C]MCC950 for imaging NLRP3-mediated inflammation in atherosclerosis.” Mol. Pharmaceutics 2023, 20, 1709–1716.
Bsharat, O; Doyle, MGJ; Munch, M; Mair, BA; Cooze, CJC; Derdau, V; Bauer, A; Kong, D; Rotstein, BH; Lundgren, RJ. “Aldehyde-catalysed carboxylate exchange in α-amino acids with isotopically labelled CO2.” Nat. Chem. 2022, 14, 1367‒1374.
Ismailani, US; Buchler, A; Farber, G; Pekošak, A; Farber, E; MacMullin, N; Suuronen, EJ; Vasdev, N; Beanlands, RSB; deKemp, RA; Rotstein, BH. “Cardiac sympathetic PET imaging with meta-[18F]fluorobenzylguanidine is sensitive to uptake‑1 in rats.” ACS Chem. Neurosci. 2021, 12, 4350–4360.
Ismailani, US; Munch, M; Mair, BA; Rotstein, BH. “Interrupted aza-Wittig reactions using iminophosphoranes to synthesize 11C-carbonyls.” Chem. Commun. 2021, 57, 5266–5269.
Kong, D; Munch, M; Qiqige, Q; Cooze, CJC; Rotstein, BH; Lundgren, RJ. “Fast carbon isotope exchange of carboxylic acids enabled by organic photoredox catalysis.” J. Am. Chem. Soc. 2021, 143, 2200–2206.
Mair, BA; Fouad, MH; Ismailani, US; Munch, M; Rotstein, BH. “Rhodium-catalyzed addition of organozinc iodides to carbon‑11 isocyanates.” Org. Lett. 2020, 22, 2746–2750.