Shuang Liu, Ph.D. Associate Professor of Health Sciences Phone: (765) 494-0236 Fax: (765) 496-1377 E-mail: liu100@purdue.edu Full directory listing

Education

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

Kim, Y. S.; Zhai, S.; Shi, J.; Hou, G. H.; Liu, S. Mechanism for myocardial localization and rapid liver clearance of ^99mTcN-MPO: a new heart imaging agent. J. Nucl. Cardiol. 2009, 36, 947-957.

Shi, J.; Wang, L.; Kim, Y. S.; Zhai, S.; Liu, Z.; Chen, X.; Liu, S. Improving tumor uptake and pharmacokinetics of ⁶⁴Cu-labeled cyclic RGD dimers with triglycine and PEG₄ Linkers. Bioconj. Chem. 2009, 20, 750-759.

Liu, S.; Kim, Y. S.; Yang, C. T.; Shi, J.; Zhai, Z.; Hou, G. Evaluation of ⁶⁴Cu(DO3A-xy-TPEP) as a PET radiotracer for monitoring tumor multidrug resistance. Bioconj. Chem. 2009, 20, 790-798.

Wang, L.; Kim, Y. S.; Shi, J.; Zhai, S.; Jia, B.; Liu, Z.; Zhao, H.; Wang, F.; Chen, X.; Liu, S. Improving tumor targeting capability and pharmacokinetics of ^99mTc-labeled cyclic RGD dimers with PEG₄ linkers. Mol. Pharm. 2009, 6, 231-245.

Shi, J.; Wang, L.; Kim, Y. S.; Zhai, S.; Liu, Z.; Chen, X.; Liu, S. Improving tumor uptake and excretion kinetics of ^99mTc-labeled cyclic Arginine-Glycine-Aspartic (RGD) dimers with triglycine linkers. J. Med. Chem. 2008, 51, 7980-7990.

Yang, C. T.; Kim, Y. S.; Wang, J.; Wang, L.; Shi, J.; Li, Z.; Chen, X.; Fan, M.; Li, J. J.; Liu, S. ⁶⁴Cu-labeled 2-(Diphenylphosphoryl)ethyldiphenylphosphonium cations as highly selective tumor imaging agents: effects of linkers and chelates on biodistribution characteristics. Bioconj. Chem. 2008, 19, 2008-2022.

Kim, Y. S.; Wang, J. J.; Broisat, A.; Glover, D. K.; Liu, S. 99mTcN-MPO: a novel cationic ^99mTc-nitrido complex with favorable properties for myocardial perfusion imaging. J. Nucl. Cardiol. 2008, 15, 535 - 546.

Liu, S. Bifunctional coupling agents for target-specific delivery of metallic radionuclides. Advanced Drug Delivery Reviews 2008, 60, 1347-1370.

Kim, Y. S.; Yang, C. T.; Wang, J. J.; Sreerama, S. G.; Cao, Q.;, Li, Z.; He, Z.; Chen, X.; Liu, S. Radiolabeled triphenylphosphonium cations as highly tumor-selective imaging agents: Effects of radiometals, bifunctional chelators and molecular charge. J. Med. Chem. 2008, 51, 2971-2984.