Photo of DiMagno, Stephen

Stephen DiMagno

Professor

Address:

Rm. 589 MC 781 833 S. Wood St.

Office Phone Voice:

(312) 413-1964

About

Research Interests: Radiopharmaceutical chemistry, medical imaging, organofluorine chemistry, kinetics, and computational chemistry

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.

Selected Publications

  1. In Vivo Biodistribution of No-Carrier-Added 6-18F-Fluoro-3,4-Dihydroxy-L-Phenylalanine (18F-DOPA), Produced by a New Nucleophilic Substitution Approach, Compared with Carrier-Added 18F-DOPA, Prepared by Conventional Electrophilic Substitution, W. Kuik, I. P. Kema, Adrienne H. Brouwers, R. Zijlma, K. D. Neumann, R. A.J.O. Dierckx, S. G. DiMagno, and P. H. Elsinga, J. Nucl. Med. 2015, 56, 106-112 (DOI: 10.2967/jnumed.114.145730)
  2. Reactivities of vinyl azides and their recent applications in nitrogen heterocycle synthesis, B. Hu, S. G. DiMagno, Org. Biomol. Chem. 2015 (Advance Article) (DOI: 10.1039/C5OB00099H)
  3. An Alternative to the Sandmeyer Approach to Aryl Iodides, B. Hu, W. H. Miller, K. D. Neumann, E. J. Linstad, S. G. DiMagno, Chem. Eur. J. 2015 (Advance Article) (DOI: 10.1002/chem.201500151)
  4. A mild and general one-pot synthesis of densely functionalized diaryliodonium salts, L. Qin, B. Hu, K. D. Neumann, E. J. Linstad, K. McCauley, J. Veness, J. J. Kempinger, S. G. DiMagno Eur JOC, 2015, 27, 5919-5924 (DOI: 0.1002/ejoc.201500986)
  5. A Practical, Automated Synthesis of meta-[18F]fluorobenzylguanidine for Clinical Use, B. Hu, A. L. Vavere, K. D. Neumann, B. L. Shulkin, S. G. DiMagno, S. E. Snyder ACS Chem. Neurosci., 2015, 6 (11), 1870-1879 (DOI: 10.1021/acschemneuro.5b00202)
  6. Microwave Assisted 18F-m-fluorobenzylguanidine (mFBG) Synthesis Using the ALP-mFBG™ Diaryliodonium Salt Precursor, A. Amor-Coarasa, J. Kelly, B. Hu, K. Neumann, S. DiMagno, J. Babich J. Nucl. Med. 2015, 56 (s3), 1044 
  7. A new efficient synthesis of no carrier added radioiodinated tracers, B. Hu, J. Blecha, K. Neumann, H. VanBrocklin, S. DiMagno J. Nucl. Med. 2014, 55 (s1), 1181
  8. Efficient automated syntheses of high specific activity 6-[18F]fluorodopamine using a diaryliodonium salt precursor By Neumann, Kiel D.; Qin, Linlin; Vavere, Amy L.; Shen, Bin; Miao, Zheng; Chin, Frederick T.; Shulkin, Barry L.; Snyder, Scott E.; DiMagno, Stephen G. From Journal of Labelled Compounds and Radiopharmaceuticals (2016), 59(1), 30-34. Language: English, Database: CAPLUS, (DOI:10.1002/jlcr.3367)
  9. Production and transport of gaseous 18F-synthons: 18F-acyl fluorides By Jiang, Huailei; DiMagno, Stephen G.; DeGrado, Timothy R. From Journal of Fluorine Chemistry (2015), 180, 181-185. Language: English, Database: CAPLUS, (DOI:10.1016/j.jfluchem.2015.09.012)

Education

  • Postdoctoral Research, University of Pennsylvania
  • Ph.D., University of California, Berkeley
  • B.A., Swarthmore College

Professional Memberships

  • Chair, Division of Fluorine Chemistry, American Chemical Society
  • Vice Chair, Membership, Division of Fluorine Chemistry, American Chemical Society
  • Executive Committee Member, Division of Fluorine Chemistry, American Chemical Society

Intellectual Property

  • Fluorination of Aromatic Rings System
  • Processes and reagents for maing diaryliodonium salts
  • Fluorination of Aromatic Rings System
  • Iodonium Cyclophanes for SECURE arene functionalization
  • Detection and quantification of anions
  • Anhydrous fluoride salts and methods for their production
  • Methods and agents for preparing 18F-radiolabeled fluorinating agents
  • Heavily fluorinated sugar analogs
  • Electron-Deficient Porphyrins and Processes and Intermediates for Preparing Same
  • Method for Preparation of Electron Deficient Porphyrins
  • Pyrrolic Compounds
  • Hyperpolarizable compounds and optoelectronic devices fabricated therefrom
  • Metal-Mediated Cross-Coupling with Ring-Metalated Porphyrins
  • Metal-Mediated Cross-Coupling with Ring-Metalated Porphyrins
  • Electron-Deficient Porphyrins and Processes and Intermediates for Preparing Same
  • Metal-Mediated Cross-Coupling with Ring-Metalated Porphyrins
  • Substituted Porphyrins, Porphyrin-Containing Polymers, and Synthetic Methods Therefor