University of Nebraska-Lincoln
818C Hamilton Hall
Lincoln, NE 68588-0304
Clinicians rely heavily on positron emission tomography (PET) imaging in the diagnosis, staging and management of cancer, cardiac, and neurological diseases. PET procedures are able to pinpoint specific biochemical activity in the body, and thus may identify disease in its earliest stages. Subsequent treatment can be easily managed by noninvasive assessment of response to therapy via PET imaging. The patient typically receives an injected radioactive drug that travels through the body and acts as a beacon, identifying tumors or the uptake of chemicals in specific tissues (dopamine to the brain, for example). The most widely used "radiotag" is an isotope of fluorine (18F) used with an analogue of glucose, 18F -FDG ([18F]-2-fluoro-2-deoxyglucose), and constitutes 94% of currently used clinical PET imaging agents. 18F-Fluorine has an attractively short half-life (109.8 minutes), which allows a patient to be quickly discharged from the hospital with no concern for residual patient radioactivity. However, the short half-life poses challenges in imaging agent preparation, as they must be made rapidly and efficiently each day near the point of use.
The DiMagno lab has developed fluorination chemistry which permits a wide range of radiotracers to be made economically on automated commercial radiosynthesis equipment with sufficient yield, activity, and purity to meet diverse clinical needs. We have developed methodology that allows for making stable, crystalline diaryliodonium salts and for using them for the efficient radiofluorination of most chemical ring structures. We have already developed precursors (destined to be tagged with radioactive isotopes) for cancer, cardiac, and brain PET imaging.
Key insights from our group’s work are: 1) low-polarity solvents suppress hitherto unknown side reactions, which severely limited the yields of fluorinated compounds obtained from diaryliodonium fluorides; 2) diaryliodonium salts undergo facile aryl exchange reactions, and 3) metal-free syntheses are key to increasing the stability of diaryliodonium salts. These insights allowed us to improve the yield of 18F-labeled compounds obtained from diaryliodonium salts dramatically. We have established collaborations with St. Jude Children's Research Hospital, UCSF, and other universities to implement our radiochemical labeling strategies more widely. Our laboratory welcomes collaborations with academic radiopharmacies.
Current research in the DiMagno group focuses on preparation and use of diaryliodonium salts in the creation of new radiotracers for PET imaging applications, improving synthesis of existing PET radiotracers, and development of novel therapeutic agents based upon PET radiotracers. We are focused on creating compounds for diagnostic scanning of cancer, depression, bio-distribution of environmental contaminants and others. Additionally, we utilize diaryliodonium salts as potent electrophilic arylating agents. Students in the DiMagno group will receive training in organic synthesis, physical organic chemistry, instrumentation and spectroscopy.
(1) Fluorinated Porphyrins and Corroles: Synthesis, Electrochemistry, and Applications, J. C. Biffinger, H. Sun, S. G. DiMagno, Fluorine in Heterocyclic Chemistry. V. Nenajdenko, Ed., 2013, Springer. (DOI: 10.1007/9783319043463_14).
(2) Replacement of BF4- by PF6- makes Selectfluor greener, Z. Jin, B. Xu, S. G. DiMagno, G. B. Hammond, J. Fluor. Chem. 2012, 143, 226–230 (DOI: 10.1016/j.jfluchem.2012.05.010)
(3) Highly Efficient, No-carrier-added F-18-Fluorodopamine Synthesis with Diaryliodonium Salts, K. D. Neumann, A. Vavere, S. Snyder, S. G. DiMagno, J. Label. Compd. Radiopharm. 2011, 54, S492 (DOI: 10.1002/jlcr.1926).
(4) Ligand Fluorination to Optimize Preferential Oxidation of Carbon Monoxide by Water-Soluble Rhodium Porphyrins, J. C. Biffinger, S. Uppaluri, H. Sun, S. G. DiMagno, ACS Catalysis, 2011, 1, 764–771. (DOI: 10.1021/cs2001187).
(5) Unprecedented Directing Group Ability of Cyclophanes in Arene Fluorinations with Diaryliodonium Salts, J. W. Graskemper, B. Wang, L. Qin, K. D. Neumann, S. G. DiMagno, Org. Lett. 2011, 13, 3158-3161 (DOI: 10.1021/ol201080c).