Steven M. Larson, MD, FACNM, FACR, Honored for Excellence in Nuclear Medicine

    NEW YORK, NY, January 30, 2015 /24-7PressRelease/ -- Steven M. Larson, MD, FACNM, FACR, Donna and Benjamen M. Rosen Chair, Lab Chief, and full member, Molecular Pharmacology and Chemistry of Sloan Kettering Institute, Director of the Ludwig Center for Radioimmunotherapy and Theranostics, and full member Molecular imaging and therapy service, (aka Nuclear Medicine Service Department of Radiology, Memorial Sloan Kettering Cancer Center, has been recognized for showing dedication, leadership and excellence in nuclear medicine.

Regarded as an expert in targeted radiotherapy and molecular imaging, as well as the care and management of patients who receive radio targeted therapy, particularly for thyroid cancer, Dr. Larson served as the chief of nuclear medicine service at MSKCC for more than 25 years. Throughout the course of his career, despite a full time clinical load, Dr. Larson maintained a research focus that has allowed doctors to have a better understanding of cancer and related molecular imaging. These research contributions were made at several distinguished medical institutions.

As a medical student, at the University of Washington, Dr. Larson invented the first practical "kit" concept for a radioactive drug used widely in current practice for detecting early nodal spread of melanoma and breast cancer by lymphoscintigraphy, 99m Technetium Sulfur colloid.

At Johns Hopkins Medical Institution, using carbon-14 labeled media and a sensitive radio detector system, Dr. Larson and his colleague Dr. Edwaldo Comargo greatly enhanced the speed of detecting viable mycobacterium species, a technology that is used widely today for detecting mycobacterium tuberculosis, including assessing drug sensitivities. While at the University of Oregon, and then the University of Washington, while pursuing a lifelong interest in the pharmacology of in vivo imaging using radiotracers, Dr. Larson discovered the mechanism of action of an early radiopharmaceutical used for tumor imaging, Gallium-67 citrate, involved translocation to the iron-binding protein transferrin, in the blood, and this finding led to the discovery of high expression of transferrin receptor, by some non-hematopoietic tumors, and a role for transferrin receptor in growth of these cells. Early laboratory studies with tumor glucose and nucleoside metabolism, in collaboration with his fellow Anthony Shields, led to the concept of exploiting the metabolic phenotype of malignancy for molecular imaging of human tumors, and suggested a role for FDG, as well as thymidine analogs as a way to exploit the Warburg effect, and enhanced DNA synthesis during tumor growth, for tumor imaging. Also, at this time, Dr. Larson with his fellow and lifelong collaborator Jorge Carrasquillo, began the development of radiolabeled tumor targeting antibody. When Dr. Larson moved to the Clinical Center, NIH, he pursued these findings with Giovanni DiChiro and these collaborative studies where among the first to show the potential value of PET FDG imaging in assessing brain tumor recurrence and response to radiation and drugs. During the time Dr. Larson was in the clinical center, he was tasked to establish a state of the Art Center for PET imaging for intramural NIH researchers. As part of that role, he worked with numerous outstanding neuroscientists in degenerative diseases of brain, such as Stanley Rappaport and Louis Sokoloff. One outcome of this work was a series of studies in Alzheimer's disease that documented the long term metabolic effects as patients progressed. This pattern of temporoparietal reduction of metabolism, was also discovered to occur in other dementing illness, and Dr. Larson and his team recognized the pattern in AIDS dementia. Dr. Larson and his colleagues, particularly Dr. Sam Broder, reported early demonstration that tyrosine kinase inhibitor drugs, active in reducing the viremia associated with AIDS, could also reverse the abnormal metabolism of brain in these patients, which paralleled clinical improvement in brain function. When Dr. Larson moved to Memorial Sloan Kettering Cancer Center, he exploited the outstanding clinical oncology environment and promoted PET imaging in oncology, extending this work to clinical aspects of common malignancies, such as thyroid, colorectal, lung, prostate and pediatric tumors. The success of this work has been the result of successful collaborations with leading experts in specialized aspects of oncology, medical physics, and radiochemistry. For example, in collaboration with Dr. Nai-Kong Cheung, a pediatric oncologist, and Dr. Ronald Finn, a radiochemist, Dr. Larson introduced the initial use of Iodine-124, a pet emitting radionuclide, as a label for tumor specific antibodies, in order to measure dosimetry of radioimmunotherapy. This is an early example of "theranostics," the use of quantitative imaging as a guide to targeted radiotherapy, in which the same chemical entity is used for diagnosis and therapy. In collaboration with Dr. Richard Robbins, Dr. Allan Ho, Dr. Michael Tuttle and James Fagin of the Department of Medicine, and Drs. John Humm and George Sgouros of Medical Physics at MSKCC, Dr. Larson developed Iodine-124, for assessing lesional dosimetry in thyroid cancer. This tool proved exceptionally useful in order to show that drugs which block the RAS-ERK pathway can restore effective therapy to thyroid cancer lesions that were previously non-avid for Iodine-131; these findings promise to revolutionize the treatment of metastatic thyroid cancer.

In collaboration with Dr. Howard Scher and Michael Morris, experts in GU oncology, Dr. Larson has developed radiotracer tools for the study of advanced prostate cancer, including an index for quantifying the extent of skeletal involvement of the tumor in bones: "the bone scan index," which has now been commercialized for widespread application, particularly in Japan and Scandinavia. Also, Dr. Larson, Dr. Scher and Morris, in collaboration with Dr. Josef Fox, developed a practical bone scan based method for measuring radiographic progression, which has been employed in multiple large-scale drug trials in advanced prostate cancer, including studies of enzalutamide and abiraterone. In addition, Dr. Larson and his colleagues in nuclear medicine and medical physics developed a method which is capable of using computerized molecular images to evaluate the multiple metastatic lesions which occur in prostate, lung and breast cancer, to study the biology of heterogeneity of metabolism of key features of tumor metabolism, such as AR axis (with FDHT), and glycolysis (with FDG), and expression of downstream AR effector molecules such as PSMA (using 89Zr-J591 antibody). The multiple lesion assessment method is called "PET-VCAR" and is commercially available from GE medical systems.

Dr. Larson remains actively involved in teaching, administration and cancer care. He has authored or co-authored more than 500 manuscripts in major peer-reviewed journals, including Science, Nature Medicine, Nature Biotechnology, Radiology, The New England Journal of Medicine and Journal of Nuclear Medicine. Dr. Larson has served on several governmental advisory committees and study sections at the National Institutes of Health, U.S. Department of Energy and U.S. Food and Drug Administration. He is currently Chairman of the Clinical Imaging Steering Committee of the National Cancer Treatment Network, (NCTN) and is a member of the NCTN advisory oversight committee.

In the coming years, Dr. Larson intends to continue conducting research and clinical trials in regard to novel radiopharmaceuticals, particularly radiolabeled antibodies and active biologicals, including immune cells and nanoparticles. A recent focus of Dr. Larson and members of his Laboratory at Sloan-Kettering Institute, has been the role of Molecular imaging and therapy in tumor immunology and has included tin development of novel antibody systems. In conjunction with Jorge Carrasquillo MD, Neil Bander of Weill Cornell Medical Center, Jedd Wolchok of the Immunology Program of SKI and Department of Medicine, a number of novel antibodies have been developed as companion diagnostics for the study of potential immunotherapy antibody approaches. Novel immunokinetics methods have been developed in collaboration with Pat Zanxonico, from Medical Physics. Promising studies of Multi-step targeting methodologies are underway in collaboration with Dr. Nai-King Cheung, David Scheinberg, and Sarah Cheal. Radiolabeling of immune cells for in vivo imaging of transport to tumor sites is also under study and had included collaborations from the Larson Lab of doctoral students and faculty, Andre Levchenko Elmer Santos, and Michelle Sadelaine, and Renier Brntjrens, of the Department of Medicine.

After developing an interest in nuclear medicine as a medical student, in 1968, Dr. Larson received an MD from the University of Washington School of Medicine, and he completed a residency in internal medicine at Virginia Mason Hospital, as well as several nuclear medicine fellowships at the National Institutes of Health. He is board certified in nuclear medicine, as well as internal medicine. His work in the field of cancer research and clinical trials has earned him the Wylie Medal from the FDA, the Louise and Lionel Berman Foundation, Inc. Award, RSNA Outstanding Researcher Award, the Inaugural Ralph G. Robinson Lecture Award from the American College of Nuclear Physicians, Peter Valk Award as the Distinguished Clinical Scientist of the Year; Society of Molecular Imaging, the George Hevesy Medals of both the US and European Societies of Nuclear Medicine, and the Cassen prize of the US Society of Nuclear Medicine. He was elected a member of the Institute of Medicine in 2005.

For more information about Steven M. Larson, MD, FACNM, FACR and Memorial Sloan Kettering Cancer Center, please visit http://www.mskcc.org.

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