An Interview with Eva Sevick-Muraca
Eva Sevick-Muraca concentrates on fluorescence-based biomedical imaging as director of the Center for Molecular Imaging at the Brown Foundation Institute of Molecular Medicine at the University of Texas Health Science Center at Houston. After earning her PhD at Carnegie Mellon University under Rakesh Jain, she did a postdoc with Britton Chance at the University of Pennsylvania and has won many awards since.
You worked with Britton Chance, who is famous in the field of biophotonics. What was it like working with him?
I used to arrive at Penn before daybreak, when Britton arrived on his bicycle, so I could greet him in his office and talk science before the onslaught of visitors he had every day. During these mornings, I would copiously take notes of our conversations in the “BC notebook” – these were lab notebooks that Britton’s staff were issued that had an emblem containing “BC” (for Britton Chance) printed on the front cover. I remember not understanding much of what he said but was confident that over time, these meetings would reveal many “gems” that would fill several scientific careers. My chore was to pick one “gem” and to develop my own program around. It turned out that the real “gem” was the “can do” spirit of creative collaboration that I learned from Britton.
You have won many awards: American Cancer Society Research Scholar, Sylvia Sorkin Greenfield Award, Elected Fellow of the American Institute of Medical and Biomedical Engineering, DuPont Young Faculty Award. Of all the awards that you’ve won, which are the most significant to you and why?
I am honored to win these awards, but probably the most exciting to me is not on this list. The award and pleasure to see former graduate students and postdoctoral fellows be productive and ethical in their careers is probably the most significant to me. But the second greatest is probably the American Cancer Society Research Scholar because I am very honored that I was chosen to receive an award to further work that is recognized by and supported by a nonscientific group, The Longaberger Foundation.
You have some patents that are un-related to your biomedical imaging work. Why did you pursue those directions?
After I was recruited from Vanderbilt to Purdue University, I was told that I would not be tenured in my discipline – then chemical engineering – unless my research pertained to the chemical process and manufacturing. Apparently, my biomedical imaging work back then was not considered “engineering” to Purdue and to many other engineering schools who also did not have a biological or biomedical engineering department or program.
What was it like being a member of a US State Department sponsored delegation to the People’s Republic of China to review international venture capital, technology transfer and intellectual property protection?
It was awe-inspiring to see the machinery of China focus and support the academic contributions to technology development, transfer and commercialization. The sheer numbers of talented persons was also awesome. However, I did also garner a healthy perception that intellectual property is only as valuable as it is protected – and the local level of protection is dependent upon our governments and how they enforce the rule of law.
In the Journal of Biomedical Optics paper, you state that you want to use the near-infrared fluorescent dye ICG to noninvasively image lymph nodes in breast cancer patients and survivors. What will this accomplish that current techniques cannot?
We sought to validate our instrument using ICG in an off-label application so we could move forward with more promising NIR imaging agents. We were pleasantly surprised that we could indeed measure noninvasive signals from microdose administration of the ICG – a dim fluorophore – and serendipitously discovered that we could image lymphatic function in humans for the first time. Hence, we believe ICG will indeed be a NIR fluorophore for imaging of lymph function, but most excitingly, the instrument can now be used with imaging agents the FDA classifies as “first in humans” administered in microdosage for molecular imaging.
You also describe a Herceptin-based imaging agent. What does that show that ICG cannot?
We conjugate this NIR fluorophore, IRDye800 CW (LiCor, Biosciences), to our targeting moieties for molecular imaging. Trastuzumab (Herceptin®, Genentech, San Francisco) is a fully humanized antibody to human epidermal growth factor-2 – a disease marker in 30 percent of all breast cancers that does not appear to be down-regulated in metastasis. As a result, it makes for a great first imaging agent for nodal staging of cancer, a program for which we have recently received a National Cancer Institute U54 center for Translational Research at the University of Texas Health Science Center’s Institute of Molecular Medicine.
How will the interplay of ICG and Herceptin-based imaging with traditional nuclear medicine techniques aid in cancer detection?
NIR fluorescence will most likely have tissue penetration issues, while nuclear techniques do not. On the flip side, NIR fluorophores do not have a physical half-life, making it a lot easier to design imaging agents with appropriate pharmacokinetics. Finally, the photon count from fluorophores is greater than radiotracers, as we point out in the JBO paper.
Do you envision that imaging with ICG will be applicable to other types of cancer besides breast cancer?
I believe NIR fluorescence imaging will have application to nodal staging in cancers where nodal staging is now performed through surgery and in cancers where surgical morbidity prevents nodal staging. I am not very confident that ICG will be used for sentinel node mapping, as agents and imaging devices already exist. I do believe targeted NIR fluorophores have a significant place in molecularly differentiating cancer-positive lymph nodes. Here, NIR fluorescence has significant opportunities for noninvasive staging, intraoperative surgical guidance for resection and surgical molecular pathology.
Your JBO paper is provocatively titled “Molecular imaging with optics: primer and case for near-infrared fluorescence techniques in personalized medicine.” How is near-infrared imaging going to enable personalized medicine?
We simply cannot biopsy repeatedly, and, in the case of metastasis, biopsy is not possible for monitoring disease marker expression and for personally tailoring therapy to the patient’s response. By using molecular imaging to evaluate longitudinally the disease marker expression, we now can begin to personalize treatment so that therapy is not prescribed but is dependent upon the patient’s response to ongoing treatment. Both nuclear and NIR fluorescence have substantial contributions to personalized medicine by partnering with molecular medicine.