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Radiopharmaceutical Chemistry
Faculty Mentors

— At the University of Missouri MU

Silvia Jurisson, Professor of Chemistry, Radiology and the Nuclear Science and Engineering Institute, couples her R&D experience in the radiopharmaceutical industry with more than 15 years in the University’s labs and classrooms. Her current research projects center on the development of diagnostic and therapeutic radiometals for medical applications, focusing on the incorporation of radiometal complexes into peptides, antibodies and other small molecules known to target melanoma, breast cancer and prostate cancer. She also investigates radioenvironmental chemistry applications for the long-lived fission product Tc-99. Projects include radionuclide production and separations, metal chelate synthesis, metal complex synthesis, radiochemical synthesis, various analyses, in vitro stability evaluations, in vitro cell binding studies (including competition studies), and in vivo biological studies in collaboration with RSI faculty. She has supervised/mentored 15 students who completed the PhD (11) and MS (4) degrees (by 2007) and currently has some 10 students currently under her wings.

Susan Lever, Associate Professor of Chemistry and Biomedical Program Director at the MURR Center, is a trained organic chemist with more than 25 years experience in the design and synthesis of metal-based radiotracers for biomedical applications. At Johns Hopkins University she developed new small molecule chelates for technetium and rhenium. More recently she has become interested in the process of in vivo complexation, where a chelating agent is administered to rid the body of unwanted metal. These pursuits are multidisciplinary, combining organic, inorganic, analytical and radiochemical skills with the development of appropriate in vitro and in vivo protocols. A high priority since coming to MU in September 2000 is the exploration and extension of the utility of radionuclides produced at MURR for radiotherapeutic applications, and the development of novel processing paradigms is critical to the dissemination of cancer-fighting radioisotopes. Central to this pursuit is the design and synthesis of novel chelating agents for reactor-based radionuclides. She has directed four PhD and two MS students and is currently advising six PhD candidates.

Timothy Hoffman is Associate Professor of Internal Medicine in the Division of Hematology/Oncology as well as of the Radiopharmaceutical Sciences Institute, and holds a joint appointment with the US Department of Veterans Affairs as Research Health Scientist and Director of the VA Biomolecular Imaging Center. He was trained as a radiopharmaceutical chemist at MU. For some 20 years he has been participating in NIH and ACS funded research on the design and development of new diagnostic and therapeutic radiopharmaceuticals, and more recently is centered on designing and developing diagnostic and therapeutic GRP receptor targeted radiopharmaceuticals. Dr. Hoffman currently is exploring the utility of molecular imaging in radiopharmaceutical development using Micro-SPECT, Micro-PET, Micro-CT and Micro-MRI technologies. Since joining the MU faculty in 2001, Dr. Hoffman has been involved in graduate and undergraduate training, most recently as a faculty mentor in a DVM/PhD comparative medicine training program in Veterinary Pathobiology.

Kattesh Katti, Professor of Physics and Radiology and Senior Research Scientist at the MURR Center, has vast experience in main group/ligand-design chemistry and coordination chemistry. The past 10 years his research has focused on design and development of novel chelating frameworks for forming radiometal complexes that have high in vivo stability; strategies for the development of new bifunctional chelating agents (BFCAs) based on novel main group ligands of phosphorus-nitrogen and phosphorus-nitrogen-silicon frameworks for conjugating biomolecules; developing methods to produce high specific activity complexes with radioactive metals with potential use in formulating diagnostic and therapeutic radiopharmaceuticals; and developing specific protocols for conjugating biomolecules with new BFCAs by synthetic routes that will not (or normally) affect their ability to bind to receptors on antigens.

John Lever is an Associate Professor of Radiology with joint appointments in Medical Pharmacology and Physiology, the Ellis Fischel Cancer Center, the Nuclear Science and Engineering Institute, and the Radiopharmaceutical Sciences Institute. His research focuses on the development of novel radioactive tracers for studies of biological recognition sites, and their use in vitro and in vivo to gain a better understanding of neoplastic disease, substance abuse and neurological function. He has expertise in medicinal chemistry, with specialties in radiopharmaceutical sciences and molecular pharmacology, and is currently studying opioid receptors and their ligands, with a focus on brain function as well as the roles opioids may play in cancer. Of particular current interest is the identification of imaging radiotracers for non-invasive detection and biochemical characterization of tumors, which may lead to improved differential diagnosis and stratification of patients for therapy. Dr. Lever has mentored over 15 postdoctoral fellows, graduate, undergraduate and medical students.

Michael Lewis, Assistant Professor in the Department of Veterinary Medicine and Surgery with joint appointments in Radiology and the Nuclear Science and Engineering Institute, has more than 16 years of experience in chemical and biological research on tumor-targeting radiopharmaceuticals, including predoctoral training at City of Hope National Medical Center and Beckman Research Institute, and postdoctoral training at Washington University School of Medicine in St. Louis, both NCI-designated Comprehensive Cancer Centers. His research has immediate relevance to the clinical imaging and therapy of cancer through attaching radiometal chelates to biomolecules that bind with a high affinity and specificity to cell surface or oncogene molecules overexpressed by tumor cells. His research program focuses on the synthesis, development, evaluation and application of metal-based radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of cancer in laboratory animal models and veterinary and human cancer patients. His group currently has multiple ongoing research projects: synthesis and evaluation of radiometal-labeled antisense agents for prognostic imaging of non-Hodgkin’s lymphoma (NHL), canine B-cell lymphoma, and other cancers; development of radiolanthanide-labeled agents for pretargeted radioimmunotherapy of human and canine carcinomas; elucidation of unique tumor cell killing mechanisms by copper radiopharmaceuticals; development of new radiation dosimetry models for internal beta minus emitter therapy in mouse models of cancer; investigation of radioimmunotherapy in combination with topoisomerase I inhibitors for treatment of ovarian cancer; evaluation of 153Sm-EDTMP for curative treatment of canine and human juvenile osteosarcoma and early metastatic prostate and breast cancer; synthesis and evaluation of 99mTc- and 188Re-cyclized somatostatin analogues for tumor imaging and therapy; and investigation of local photodynamic therapy for squamous cell carcinoma. There are several advantages to evaluating tumor-targeting radiopharmaceuticals in veterinary patients, including the availability of more realistic animal models, patients with minimal treatment history, reduced regulatory burden, and shorter study endpoints. This process facilitates translational research leading to human clinical trials.

Thomas Quinn, Professor of Biochemistry, Radiology and the Nuclear Science and Engineering Institute, has expertise in the fields of protein/peptide design and characterization, for radiopharmaceutical development and for basic cancer research. He couples molecular modeling with high field NMR solution structural analysis to design peptide molecules that target specific cellular proteins such as G-protein coupled receptors. In a complementary approach, he screens random peptide bacteriophage libraries to identify peptides that target receptors, carbohydrates and specific cellular processes like adhesion. Dr. Quinn has experience in both structure-based and combinatorial-based strategies designed to discover targeting molecules with high specificities and affinities, and in using peptides to inhibit tumor-cell adhesion, an early step in the metastatic cascade.. He has used radiolabeled peptides to image primary and metastatic melanoma in mouse melanoma models using micro-SPECT and micro-PET, and has shown therapeutic efficacy in melanoma bearing mice with the same family of peptides radiolabeled with other isotopes.

C. Jeff Smith is an Assistant Professor of Radiology with joint appointments in the MURR Center, Radiopharmaceutical Sciences Institute and Nuclear Science and Engineering Institute, as well as the Harry S. Truman Memorial Veterans’ Administration Hospital. He has graduate training in inorganic/organometallic/main group chemistry, with expertise in the design and development of polydentate, aqueous-soluble, phosphane containing ligands for Tc and Re. Dr. Smith has significant experience in radiopharmaceutical development, including isotope processing and purification, tracer level and macroscopic metallation of small ligand frameworks and various bioconjugates, and in vitro and in vivo diagnostic/therapeutic radiopharmaceutical applications. Recently, Dr. Smith is focusing on the design and development of radiolabeled analogs of bombesin (BBN) with various radionuclides and was responsible for the basic science investigations and identification of a 99mTc-N3S-BBN construct used in Phase I/II clinical trials in Europe.

Wynn Volkert is Curator’s Professor of Radiology, Chemistry and Biochemistry and Senior Research Career Scientist at Harry S. Truman Memorial Veterans’ Administration Hospital. For the past 25 years his research has focused on the development of new diagnostic and therapeutic radiopharmaceuticals, including the design of effective chelating frameworks for various radionuclides, labeling of biomolecules and performance of pharmacokinetic and therapeutic studies of radiotracers in animal models. Dr. Volkert works closely with faculty and staff in Chemistry and at the MURR Center in the application of beta-particle emitting radionuclides for potential therapeutic applications.
Earlier in his research career, he was co-developer (along with Drs. David Troutner and Richard Holmes) of 99mTc-PnAO, the compound that formed the basis for development of 99mTc-HMPAO (Ceretec™), the first 99mTc radiopharmaceutical for cerebral perfusion imaging. He was also co-developer of 153Sm-EDTMP (Quadramet®), a beta emitting therapeutic agent approved by the FDA for bone cancer pain palliation. His experience and background provide the essential ingredients in enabling him to direct and mentor PhD students in chemistry in their dissertation research projects in the area of radiopharmaceutical chemistry. Dr. Volkert’s current research program is directed toward developing radiotracers for diagnostic molecular imaging agents and in vivo targeted therapeutic radiopharmaceuticals using a variety of radionuclides, and primarily involves design, development and study of radiolabeled peptides that specifically target GC-C receptors that are overexpressed on human colon cancer cells, and GRP receptors that are overexpressed on human breast and prostate cancer cells.

— At Brookhaven National Laboratory Brookhaven Logo

Joanna Fowler is Senior Chemist and Director of the Center for Translational Neuroimaging at Brookhaven National Laboratory, and is an Adjunct Professor of Chemistry at SUNY-Stony Brook. She is trained as a synthetic organic chemist with more than 30 years of experience in the development and applications of radiotracers labeled with carbon-11 and fluorine-18. Her research interests include radiotracer design and synthesis, studies of the mechanisms of action of therapeutic drugs and drugs of abuse, and imaging specific molecular targets in the brain and in the body. She has had a special interest in stimulant drug action, on developing radiotracers for imaging and quantifying enzyme activity, and on the use of PET imaging to probe drug pharmacokinetics and pharmacodynamics. An overarching goal of her research is to develop the scientific tools needed to characterize the molecular changes underlying psychiatric disorders and neurodegenerative disorders, and to use imaging to facilitate the development of therapeutic drugs and their introduction into the practice of health care. She is currently mentoring two post-doctoral fellows, two SUNY-Stony Brook Chemistry graduate students and is co-mentor for one Biomedical Engineering graduate student.

Richard Ferrieri is the BNL Site Director for the Nuclear Chemistry Summer School, as well as the Supervisor of Operations for the BNL PET Radiotracer Laboratory. He is trained as a physical/organic chemist with 30 years of experience in nuclear and radiochemistry. Recent research interests lie in the application of short-lived radiotracers for quantifying dynamic processes in living systems, including plant and animal models, as well as in non-living systems including contaminant flow and biodegradation within environmental sediments. His major focus is in radiotracer design and synthesis applied to the understanding of how chemical structure influences biological activity of certain molecules within living systems, and particularly in how certain hormones, acting as chemical signals in key regulatory control points of these systems, impact metabolism and/or bio-distribution of essential elements for sustaining life. Recent success in this is radiolabelling several key phytohormones linked to plant defense, growth and development and using them to identify control points within the Calvin Cycle. This work is being extended to certain structural analogs that may share certain commonalities in the regulatory processes of both plants and animals. More current interests include designing new radiotracers for probing membrane status non-invasively, and designing radiolabeled nanoparticles to investigate their bio-distribution and potential therapeutic effects on membrane status for future drug delivery design.

David Schlyer is a Chemist and head of the BNL Cyclotron, and is an Adjunct Assistant Professor of Biomedical Engineering at SUNY-Stony Brook. He is a trained inorganic and physical chemist with over 25 years experience in radioisotope production for biomedical applications, and has performed extensive research in cyclotron target design and radioisotope processing. More recently, Dr. Schlyer is developing new methods of radioisotope imaging in small animals, multi-disciplinary pursuits that combine physics, chemistry and instrumentation in novel imaging modalities. A high priority is the exploration and extension of the utility of radionuclides produced at BNL for both imaging and radiotherapeutic applications. He has directed one PhD student and is currently advising five PhD candidates.

Stephen Dewey is a neuroanatomist and Senior Scientist who leads BNL’s effort in radiotracer evaluation. His research centers on studies of the neurobiology of addictive disorders and the development of treatments for addiction by integrating PET, microPET, microdialysis and behavioral models to understand the changes in brain chemistry that occur in addiction. He holds adjunct appointments in the departments of Neurobiology and Behavior and Pharmacology at SUNY-Stony Brook and mentors many students at the high school, undergraduate and graduate levels, three of whom have obtained their PhD in the last two years. In addition he participates in outreach to thousands of schoolchildren each year speaking about neuroscience and substance abuse.

— At the National Cancer Institute Brookhaven Logo

Martin Brechbiel, Lead Organic Chemist and Chief of the Radioimmune and Inorganic Section of the National Cancer Institute in Bethesda, MD, is a trained organic chemist with more than 20 years of experience in the design and synthesis of novel reagents. Before joining the NCI, he was a synthetic chemist in the pesticide industry. His work includes the design and synthesis of novel bifunctional chelating agents for biomedical applications, with a focus on the development of novel chelating agents for both beta-emitting radiolanthanides and alpha-emitters. Out of these efforts has emerged the chemistry that is employed for the first radiolabeled therapeutic monoclonal antibody for treating non-Hodgkin’s Lymphoma. The Section has a lengthy involvement in the creation of novel MRI contrast agents, most currently focusing on macromolecular dendrimers. Dr. Brechbiel’s research has provided numerous unique bifunctional chelating agents for a range of radionuclides and recently he has become interested in the development of novel small molecule chelating agents that either target intracellular Fe as a therapeutic or target Cu to inhibit angiogenesis. He has expanded studies of therapeutic alpha-emitting radionuclides to include the development of protein or peptide linking molecules for At-211 as well as study of the fundamental coordination chemistry of At. These are multidisciplinary pursuits that combine organic, inorganic, analytical and radiochemical skills and include the execution of the appropriate in vitro and in vivo biological experimentation protocols.

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