个人简介
B.Sc., University of King’s College and Dalhousie University
Ph.D., University of Toronto
Postdoctoral Fellowship, Harvard Medical School and Massachusetts General Hospital
研究领域
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) or single-photon emission computed tomography (SPECT) contain short-lived radioactive isotopes and engage in highly specific and selective molecular 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 imaging analysis. From a foundation in all aspects of radiopharmaceutical chemistry, our laboratory seeks to develop strategies and methods for application ultimately in nuclear molecular imaging research 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 (20 and 110 minute half-lives, respectively);
Targeted and selective imaging probes for biochemical processes of relevance to cardiology, neuroscience, and/or oncology preclinical and translational research and diagnosis;
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.
近期论文
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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, in press. doi: 10.1039/C6SC00197A.
Wang, L; Jacobsen, O; Advic, D; Rotstein, BH; Weiss ID; Collier TL; Chen X; Vasdev, N; Liang, SH. “Ortho-stabilized 18F-azide click agents and application in PET imaging of single-stranded DNA aptamer.” Angew. Chem. Int. Ed. 2015, 54, 12777–12781.
Rotstein, BH; Liang, SH; Belov, VV; Livni, E; Levine, DB; Bonab, AA; Papisov, MI; Perlis, RH; Vasdev, N. “Practical radiosynthesis and preclinical neuroimaging of [11C]isradipine, a calcium channel antagonist.” Molecules 2015, 20, 9551–9559.
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. Pharmaceutics2014, 11, 3832–3838.
Rotstein, BH; Hooker, JM; Woo, J; Collier, TL; Brady, TJ; Liang, SH; Vasdev, N. “Synthesis of [11C]bexarotene by Cu‑mediated [11C]carbon dioxide fixation and preliminary PET imaging.” ACS Med. Chem. Lett.2014, 5, 668–672.
Rotstein, BH; Zaretsky, S; Rai, V; Yudin, AK. “Small ring heterocycles in multicomponent reactions.” Chem. Rev. 2014, 114, 8323–8359.
Holland, JP; Liang, SH; Rotstein, BH; Collier, TL; Stephenson, NA; Greguric, I; Vasdev, N. “Alternative approaches for PET radiotracer development in Alzheimer’s disease: Imaging beyond plaque.” J. Labelled Compd. Radiopharm. 2014, 57, 323–331.
Liang, SH; Collier, TL; Rotstein, BH; Lewis, R; Steck, M; Vasdev, N. “Rapid microfluidic flow hydrogenation for reduction or deprotection of 18F-labeled compounds.” Chem. Commun.2013, 49, 8755–8757.
Rotstein, BH; Liang, SH; Holland, JP; Collier, TL; Hooker, JM; Wilson, AA; Vasdev, N. “11CO2 fixation: A renaissance in PET radiochemistry.” Chem. Commun.2013, 49, 5621–5629.
Rotstein, BH; Mourtada, R; Kelley, SO; Yudin, AK. “Solvatochromic reagents for multicomponent reactions and their utility in the development of cell-permeable macrocyclic peptide vectors.” Chem. Eur. J.2011, 17, 12257–12261.
Rotstein, BH; Rai, V; Hili, R; Yudin, AK. “Synthesis of peptide macrocycles using unprotected amino aldehydes.” Nature Protoc. 2010, 5, 1813–1822.