Michael F. Tweedle, PhD
Professor and Stefanie Spielman Chair in Cancer Imaging
Department of Radiology
Molecular Imaging Agent Laboratory
The Ohio State University Medical School
Biomedical Research Tower, Rm 710
460 W. 12th Ave
Columbus, OH 43210
Imaging of cancer using biochemically targeted imaging and theranostic pharmaceuticals
Intra-operative optical surgical navigation and specimen evaluation
Krishan Kumar, Ph.D. – Associate Professor, Research
Shankaran Kothandaraman, Ph.D. – Research Scientist
Haiming Ding, Ph.D. – Research Scientist
Ajay Shrivastava, Ph.D. – Post Doc
Shu-Huei Wang, Ph.D. – Post Doc
Keisha Milum – Research Assistant
The work in my group always begins with a clinical problem that appears to be solvable by creating a new imaging pharmaceutical. Projects exist in breast, prostate and head and neck cancers. Neither early breast cancers nor any prostate cancers are specifically imaged with PET to verify early stage disease due to insufficient sensitivity (prostate) or specificity (breast) of the existing imaging pharmaceuticals that are effective in many other cancers. Several hormone peptide receptors are independently overexpressed in breast and prostate cancers, and we seek to use combinations of these relatively small peptides as imaging agents, and with therapeutic isotopes, as theranostics, molecules that simultaneously image and destroy cancer cells in vivo. The work involves synthesis of the candidates, human cancer cell culture, receptor cell binding, radioactive labeling, and in vivo imaging in small animal models. Students learn the basics of each subfield as they create, test, and refine new imaging pharmaceuticals. In Optical Surgical Navigation, targeting molecules are labeled with Near Infrared fluorescent molecules that allow surgeons to visualize cancer cells or other tissue types in real time as they operate directly or using a surgical robot. Many of the same targeting peptides or antibody fragments are used in both project types, and dual modality PET/Optical probes are possible.
Reviews and Chapters
M.F. Tweedle (2009). Peptide - targeted diagnostics and radiotherapeutics. Accounts of Chemical Research, 42(7): 958-68.
K.E. Linder, E. Metcalfe, P. Nanjappan, T. Arunachalam, K. Ramos, T.M. Skedzielewski, M.F. Tweedle, A.D. Nunn, R.E. Swenson (2011). Synthesis, In Vitro Evaluation and In Vivo Metabolism of Fluor/Quencher Compounds Containing IRDye 800CW and Black Hole Quencher-3 (BHQ-e). Bioconj. Chem., 22(7): 1287-97.
R.X. Xu, J. Xu, T. Zuo, R. Shen, T.H. Huang, M.F. Tweedle (2011). Drug-loaded biodegradable microspheres for image-guided combinatory epigenetic therapy in cells. J. Biomed. Optics, 16:02050.
Multivalent targeting peptides
M.A. Von Wronski, N. Raju R. Pillai; N.J. Bogdan; E.R. Marinelli; P. Nanjappan; K. Ramalingam; K. Arunachalam; S. Eaton; K. Linder; F. Yan; S. Pochon,; A.D. Nunn; M.F. Tweedle (2006). Tuftsin binds neuropilin-1 through a sequence similar to that encoded by exon 8 of VEGF. J. Biol. Chem, 281(9): 5702-10.
A. Shrivastava, M.A. von Wronski, A.K. Sato, D.T. Dransfield, D. Sexton, N. Bogdan, R. Pillai, P. Nanjappan, B. Song, M. Marinelli, D. DeOliveira, C. Luneau, M. Devlin, M. Muruganandam, A. Abujoub, G. Connelly, Q. Wu, G. Conley, Q. Chang, M.F. Tweedle, R.C. Ladner, R. Swenson, A.D. Nunn (2005). A distinct strategy to generate high affinity peptide binders to receptor tyrosine kinases. Protein Engineering, Design and Selection, 18(9): 417-24.
Hormone peptide theranostics
L. E. Lantry, E Cappeletti, M. Maddalena, J. S. Fox, W. Feng, J. Chen, R. Thomas, S. M. Eaton, N. J. Bogdan, T. Arunachalam, J. C. Reubi, N. Raju, L. Kattuada, K. E. Linder, R. E. Swenson, M. F. Tweedle, A. D. Nunn (2006). LuAMBA: Synthesis and Characterization of a Selective 177Lu-Labeled GRP-R Agonist for Systemic Radiotherapy of Prostate Cancer. J. Nucl. Med., 47(7):1144 – 52.
J. Chen, K. E. Linder, A. Cagnolini, E. Metcalfe, N. Raju, M. F. Tweedle, R. E. Swenson (2008). Synthesis, Stabilization and Formulation of [177Lu]Lu-AMBA, a Systemic Radiotherapeutic Agent for Gastrin Releasing Peptide Receptor Positive Tumors. J. Applied Radiation Isotopes, 66: 497-505.
M. E. Maddalena, J. Fox, J. Chen, W. Feng, A. Cagnolini, K. E. Linder, M. F. Tweedle, A. D. Nunn, Laura E. Lantry (2009). 177Lu-AMBA Biodistribution, Radiotherapeutic Efficacy, Imaging and Autoradiography in Prostate Cancer Models with Low GRP-R Expression. J. Nucl. Med., 50(12):2017-24.
Radiotracers and MRI agents
Ghosh, M. Haverick, K. Stump, X. Yang, M.F. Tweedle, J.E. Goldberger (2012). Fine-Tuning the pH Trigger of Self-Assembly. J Am Chem Soc, 134(8):3647-50.
M.F. Tweedle, P. Wedeking, K. Kumar (1995). Biodistributions of Radiolabeled, Formulated Gadopentetate, Gadoteridol, Gadoterate and Gadodiamide in Mice and Rats. Invest. Radiol., 30(6):372-80.