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School of Health Sciences Personnel - Shuang Liu

Shuang Liu, Ph.D.
Professor of Health Sciences
Phone: 765-494-0236
Fax: 765-496-1377

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B.Sc. - 1982 - Shandong Normal University (P.R. China).
M. Sc. - 1985 - Shandong Medical University (P. R. China)
Ph. D. - 1990 - Memorial University of Newfoundland, St. John's, Newfoundland
1991-1993 NSERC Postdoctoral Fellow, University of British Columbia
1993-1997 Senior Research Scientist, DuPont Merck Pharmaceuticals Company
1997-2001 Principal Research Scientist, DuPont Pharmaceuticals Company
2002 Principal Investigator, Bristol-Myers Squibb Medical Imaging

Research: Radiopharmaceutical Chemistry; Development of new target-specific radiopharmaceuticals, and coordination chemistry of metallopharmaceuticals

Dr. Liu's research interests include receptor-based target radiopharmaceuticals, new bifunctional chelators, development of new techniques for the radiolabeling of small biomolecules, formulation development, design/synthesis/evaluation of metal complexes as MRI contrast agents for cardiac perfusion imaging, and fundamental coordination chemistry of metallopharmaceuticals. He is a member of the Advisory Board of Bioconjugate Chemistry. He is the author or co-author over 90 scientific publications, and has been granted 30 US patents and foreign patent applications.

Projects related to target-specific radiopharmaceuticals involve design, synthesis, and biological evaluation of radiolabeled receptor ligands that bind to receptors expressed on the surface of tumor cells. The use of metallic radionuclides offers many opportunities for designing new radiopharmaceuticals by modifying the coordination environment around the metal with a variety of chelators. The coordination chemistry of metallic radionuclide will determine the geometry of the metal chelate and influence solution stability of the radiopharmaceutical. Different metallic radionuclides have different coordination chemistries, and require bifunctional chelators (BFCs) with different donor atoms and ligand frameworks. For target-specific radiopharmaceuticals, the biodistribution will be affected by the metal chelate and the targeting biomolecule (BM). This is especially true for radiopharmaceuticals based on small molecules such as peptides, due to the fact that in many cases the metal chelate contributes greatly to the overall size and molecular weight. Therefore, the design and selection of the BFC is very important for the development of a new radiopharmaceutical.

Development of new bifunctional chelators and new radiolabeling techniques is an important part of our radiochemistry research. It involves synthesis and characterization of new chelators and metal chelates at both macroscopic level and tracer (concentration typically in the range of 10-6 - 10-12 M depending on the half-life of the radionuclide) levels using conventional chromatographic (TLC and HPLC) and spectroscopic methods (IR, NMR, and MS), or more specialized analytical techniques, such as radio-HPLC and radio-LC-MS.

Our current research also involves design, synthesis, and biological evaluation of paramagnetic metal (such as Gd3+, Mn2+ and Fe3+) chelates as MRI contrast agents. These activities require a good understanding of fundamental coordination chemistry of paramagnetic metals, such as Gd3+, Mn2+ and Fe3+. Characterization of metal chelates requires the use of spectroscopic methods (IR, ESR, and MS), and X-ray crystallography. The biological data is collected via internal or external collaborations. These data are useful for elucidation of structure-activity relationships, and provide the base for selection of lead compound(s), which will undergo extensive biological evaluations in more sophisticated animal models.

Representative Publications

Ji, S.; Zhou, Y.; Shao, G.; and Liu, S.  (HYNIC)2K: A bifunctional chelator useful for 99mTc-labeling of small biomolecules.  Bioconjugate Chem. 2013, 24: 701−711.

Shao, G.; Zhou, Y.; and Liu, S.  Monitoring glioma growth and tumor necrosis with u-SPECT-II/CT for by targeting integrin αvβ3Mol. Imaging 2013, 12: 39-48.

Yu, Z.; Ananias, H. J. K.;  Carlucci, G.; Dierckx, R. A. J. O.; Liu, S.; Helfrich, W.; Wang, F.; de Jong, I. J.; Elsinga, P. H.  Evaluation of a 99mTc labeled Bombesin homodimer for GRPR imaging in prostate cancer.  Amino Acids 2013, 44: 543–553.

Zhou, Y.; Shao, G.; Wang, F.; and Liu, S.  Imaging breast cancer lung metastasis by u-SPECT-II/CT with an integrin αvβ3-targeted radiotracer 99mTc-3P-RGD2Theranostics 2012, 2:577-587.

Yan, X.; Zhou, Y.; and Liu, S.  Optical imaging of tumors with copper-labeled rhodamine derivatives by targeting mitochondria.  Theranostics 2012, 2: 988-998.

Zhou, Y.; Kim, Y. S.; Lu, X.; and Liu, S.  Evaluation of 99mTc-labeled cyclic RGD dimers: impact of cyclic RGD peptides and 99mTc chelates on biological properties.  Bioconjugate Chem. 2012, 23, 586−595.

Zhou, Y.; Kim, Y. S.; Chakraborty, S.; Shi, J.; Gao, H.; and Liu, S.  99mTc-Labeled cyclic RGD peptides for noninvasive monitoring of tumor integrin avb3 expression. Mol. Imaging 2011, 10: 386-97. 

Fang, W.; He, J.; Kim, Y. S.; Zhou, Y.; and Liu, S.  Evaluation of 99mTc-labeled cyclic RGD peptide with a PEG4 linker for thrombosis imaging: comparison with DMP444.  Bioconjugate Chem. 2011, 22, 1715–1722.

Zhou, Y.; and Liu, S.  64Cu-Labeled phosphonium cation as potential PET radiotracers for tumor imaging.  Bioconjugate Chem. 2011, 22, 1459–1472.

Zhou, Y.; Kim, Y. S.; Shi, J.; Chen, X.; and Liu, S.  64Cu-labeled Lissamine Rhodamine B: a PET radiotracer targeting tumor mitochondria.  Mol. Pharm.  2011, 8, 1198-1208.

This record was last updated on Jun 6, 2013 at 11:41 AM
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