Engineering near-infrared fluorescence optical instrumentation and designing "first-in-humans" imaging agents for translational studies

Wednesday, November 7, 2012

1:30pm | Schiciano Auditorium - Side B

Presenter

Eva M. Sevick , Professor of Molecular Medicine and Kinder Distinguished Chair; Director, Center for Molecular Imaging; Director, NCI Center in Network for Translational Research

Microdosing refers to the trace administration defined by the FDA as 1/100th a pharmacological dose, less than 100 micrograms, or less than 30 nanomoles of a protein based agent.  Microdosing enables radiolabeling of drug candidates to secure biodistribution from nuclear imaging techniques in routine exploratory clinical studies and, since adverse events may not be expected with trace administration, represents a smart regulatory pathway to “de-risk” new imaging technologies and “first-in-humans” imaging agents.  While nuclear imaging techniques benefit from microdosing and trace administration of radiolabeled, molecularly targeted imaging agents, the fluorescence optical imaging community has yet to recognize the beneficial strategies of microdosing through the design of imaging devices that have sensitivities comparable to that obtained with nuclear imaging modalities. 

Figure caption:  NIRFLI of lymphatic in the dorsal foot of a normal healthy subject (left) and of a subject with a congenital lymphatic disorder. 

Herein, we present clinical results of non-invasive near-infrared fluorescence lymphatic imaging (NIRFLI) that employ off-label microdose administrations of indocyanine green (a poor, non-targeted near-infrared fluorophore) to demonstrate imaging device sensitivity.  While the clinical images are striking and lend themselves to discovery in translational research, they more importantly point to strategies for developing molecularly targeted near-infrared fluorescence imaging agents.  These studies succinctly show the feasibility of future near-infrared fluorescence imaging with trace administration of “first-in-human,” molecularly-targeted, near-infrared imaging agents.  In the second half of the presentation, strategies of imaging agent design, validation, and clinical translation based upon microdosing are illustrated by example of a specific imaging agent slated for clinical translation in the area of cancer lymph node staging and intraoperative tumor margin identification.

Eva M. Sevick, Ph.D. is Professor in Molecular Medicine and Kinder Distinguished Chair at the University of Texas Health Science Center’s Institute of Molecular Medicine (IMM) where she currently directs the Center for Molecular Imaging.   At the IMM she leads the National Cancer Institute Center for Translational Research which focuses upon the development and validation of new imaging instrumentation, algorithms, and imaging agents and their clinical translation.  She has pioneered the development of near-infrared fluorescence optical imaging and tomography for molecular imaging and currently has two clinical trials underway at the University of Texas Health Science Center and Memorial Hermann Hospital that employ the technology for novel diagnostic imaging of lymphatic function.  Dr. Sevick is currently collaborating with bio-informatics experts to use near-infrared fluorescence lymphatic imaging for phenotyping and next generation sequencing techniques to genotype families with rare lymphatic disorders.  Her team is active in preclinical, small animal imaging/tomography with nuclear and optical techniques and is pioneering diagnostic imaging for nodal staging in cancer.

Dr. Sevick received her Ph.D. in Chemical Engineering at Carnegie Mellon University under the tutelage of Dr. Rakesh Jain, her post-doctoral training in Biochemistry and Biophysics at the University of Pennsylvania from Dr. Britton Chance, and has served on the engineering faculties at Vanderbilt, Purdue, and Texas A&M and on the medical school faculties at Baylor College of Medicine and University of Texas Health Science Center.   She is past recipient of the National Science Foundation Young Investigator Award, the National Institutes of Health Research Career Award, and the American Cancer Society Research Scholar Award and has served as an appointed member of the NIH Biomedical Imaging Study section and of the California Breast Cancer Research Program, Chair of the NIH Clinical Molecular Imaging Probes Study Session and of the US Army Medical and Materiel Command Prostate Cancer Imaging, associate editor of the IEEE Transactions of Medical Imaging, and past elected officer of the Society of Nuclear Medicine Center for Molecular Imaging Innovation and Translation Board and the Society of Molecular Imaging.  She has contributed over 150 peer-reviewed publication, 150 invited seminars, lectures, and keynote addresses, and has conducted 10 IND studies with six different institutions on the Texas Medical Center.