- Email: [email protected]
Nanotechnology Molecular Medicine and Radiology
HEARD ON THE CAMPUS
DONALD P. HARRINGTON, MD, MA
Nanotechnology Molecular Medicine and Radiology We live in a time of great change. The many advances in medical imaging are examples of the process. We are, it seems, assaulted on all sides by new concepts and ideas that at first seem random and disordered. On closer evaluation, they may form with our input the future direction of our medial imaging specialty. We must be willing to examine and evaluate the new developments. Will we embrace and develop these ideas to further our practice or leave it to others? The purpose of this month’s column is to explore ideas related to nanotechnology and how this developing technology may affect the future of radiology. As in all complex systems, many concepts play an indirect role in future development, and this is true for health care imaging. They include discoveries in genomics and proteinomics and the development of personalized medicine as a paradigm for tomorrow’s health care. Although such a practice is in the future, the idea gives us a goal and a hint of what’s to come. Personalized medicine can be described as medicine directed toward a single individual, not a group of individuals such as middle-aged men. The task is to identify the health care profile unique to an individual. To accomplish the goal, we must work at the molecular level, which is also the realm of nanotechnology. The technology presents the opportunity to combine the diagnosis of an individual’s disease and, in some cases, its therapy. The National Science Foundation’s [1] description of nanotechnology is as follows: 578
Research and technology development at the atomic, molecular or macromolecular levels, in the length scale of approximately 1 to 100 nanometer range, to provide a fundamental understanding of phenomena and materials at the nanoscale and to create and use structures, devices, and systems that have novel properties and functions because of their small or intermediate size.
Our exploration at this scale is just beginning. Developments include biomarkers for diagnosis and nanoparticles that are used for their therapeutic effects. These biomarkers and molecular diagnostics will in turn support drug discovery and improve drug delivery, all of which are important components of personalized medicine. Combining diagnostic and therapeutic capabilities into one package makes health care more effective and less costly. An example of the possibilities tested in vitro is gold nanorods used in conjunction with laser light. When appropriately constructed, the gold nanorods will both absorb and scatter light in the near infrared spectrum (650 to 900 nm). After construction, the nanorods are conjugated with antiepidermal growth factor receptor monoclonal antibodies and then incubated with 3 epithelial cell lines, 2 of which are malignant and 1 normal. The malignant cells are distinguishable from the normal cells, and when exposed to continuous red laser light at 800 nm, the malignant cells are destroyed with half the energy to fatally affect the normal cells. This method may provide future diagnosis and therapy in one sitting [2]. Another example of the use of nanoparticles is described in a metaanalysis of studies using ferumoxtran-10, an ultrasmall superparamag-
netic iron oxide contrast agent for the detection of lymph-node metastases. The study controls were unenhanced magnetic resonance imaging (MRI) and histology. Overall sensitivity and specificity for nanoparticles was 0.88 and 0.96, respectively, compared with unenhanced MRI, which had sensitivity and specificity of 0.63 and 0.93, respectively. The authors concluded that iron-oxide-enhanced MRI had higher diagnostic precision than unenhanced MRI and allowed for the anatomic and functional definition of the disease [3]. A final example also of the use of iron oxide as a contrast agent is the magnetic labeling of migrating cells that are followed by MRI. Cell trafficking is an important component of systems biology and the future clinical use of stem and progenitor cells. Early studies in central nervous system disease models have demonstrated good spatial resolution and cell tracking over time. The authors of one study speculated that this method will be used in the foreseeable future to monitor cell therapy [4]. Support for nanotechnology is widespread at the National Institutes of Health and individual institutes and beyond. The National Cancer Institute developed the Centers of Cancer Nanotechnology Excellence. The program has been in effect for 7 years and has resulted in 8 centers, the newest of which is at the University of California, San Diego [5]. The National Institutes of Health Roadmap for Medical Research is another source of support for nanotechnology, with the Nanomedicine Roadmap Initiative. The goal of this initiative is to describe biomolecular systems in
© 2006 American College of Radiology 0091-2182/06/$32.00 ● DOI 10.1016/j.jacr.2006.05.004
Heard on the Campus 579
systems engineering terms, the endpoint of which is to create blueprints for nanomachines and structures to manipulate the systems for disease treatment and the repair of damaged cells and tissues [6]. Governmental support is not the only source of interest in nanotechnology for imaging. GE’s Global Research Center is involved in long-range nanotechnology nanoparticles. How can we as radiologists contribute to the various efforts in the development of our specialty? Learning about and developing a
practice of molecular imaging is one step. Supporting efforts by radiology societies such as the ACR and the Radiological Society of North America also are important steps. Only we can ensure our future in the new imaging environment. REFERENCES 1. National Science Foundation. Nanotechnology definition (NSET, February 2000). Available at: http://www.nsf.gov/crssprgm/ nano/reports/omb_nifty50.jsp. 2. Huang X, El-Sayed IH, Qian W, El-Sayed MA. Cancer cell imaging and photothermal
therapy in the near-infrared region by using gold nanorods. J Am Chem Soc 2006;128:2115-20. 3. Will O, Purkayastha S, Chan C, et al. Diagnostic precision of nanoparticle-enhanced MRI for lymph node metastases: a meta-analysis. Lancet Oncol 2006;7:52-60. 4. Bulte JW, Kraitchman, DL. Monitoring cell therapy using iron oxide MR contrast agents. Curr Pharm Biotechnol 2005;5:567-84. 5. National Cancer Institute. Centers of Cancer Nanotechnology Excellence (CCNEs). Available at: http://nano.cancer.gov/programs/ ccne_overview.asp. 6. National Institutes of Health, Office of Portfolio Analysis and Strategic Initiatives. Nanomedicine: overview. Available at: http:// nihroadmap.nih.gov/nanomedicine/.
Donald P. Harrington, MD, MA, University Hospital, Department of Radiology, Health Sciences Center, Level 4, Room 120, Stony Brook, NY 11794-8460; e-mail: [email protected]; Institute of Biomedical Imaging and Bioengineering, 6707 Democracy Boulevard, Suite 202, MSC-5477, Bethesda, MD 20892; Columbia Presbyterian Medical Center, Informatics, Vanderbilt Clinic 543, 622 West 168th Street, New York, NY 10032. This column was written in a personal capacity and does not represent the opinions of the National Institutes of Health, the US Department of Health and Human Services, or the Federal Government.
DONALD P. HARRINGTON, MD, MA
Nanotechnology Molecular Medicine and Radiology We live in a time of great change. The many advances in medical imaging are examples of the process. We are, it seems, assaulted on all sides by new concepts and ideas that at first seem random and disordered. On closer evaluation, they may form with our input the future direction of our medial imaging specialty. We must be willing to examine and evaluate the new developments. Will we embrace and develop these ideas to further our practice or leave it to others? The purpose of this month’s column is to explore ideas related to nanotechnology and how this developing technology may affect the future of radiology. As in all complex systems, many concepts play an indirect role in future development, and this is true for health care imaging. They include discoveries in genomics and proteinomics and the development of personalized medicine as a paradigm for tomorrow’s health care. Although such a practice is in the future, the idea gives us a goal and a hint of what’s to come. Personalized medicine can be described as medicine directed toward a single individual, not a group of individuals such as middle-aged men. The task is to identify the health care profile unique to an individual. To accomplish the goal, we must work at the molecular level, which is also the realm of nanotechnology. The technology presents the opportunity to combine the diagnosis of an individual’s disease and, in some cases, its therapy. The National Science Foundation’s [1] description of nanotechnology is as follows: 578
Research and technology development at the atomic, molecular or macromolecular levels, in the length scale of approximately 1 to 100 nanometer range, to provide a fundamental understanding of phenomena and materials at the nanoscale and to create and use structures, devices, and systems that have novel properties and functions because of their small or intermediate size.
Our exploration at this scale is just beginning. Developments include biomarkers for diagnosis and nanoparticles that are used for their therapeutic effects. These biomarkers and molecular diagnostics will in turn support drug discovery and improve drug delivery, all of which are important components of personalized medicine. Combining diagnostic and therapeutic capabilities into one package makes health care more effective and less costly. An example of the possibilities tested in vitro is gold nanorods used in conjunction with laser light. When appropriately constructed, the gold nanorods will both absorb and scatter light in the near infrared spectrum (650 to 900 nm). After construction, the nanorods are conjugated with antiepidermal growth factor receptor monoclonal antibodies and then incubated with 3 epithelial cell lines, 2 of which are malignant and 1 normal. The malignant cells are distinguishable from the normal cells, and when exposed to continuous red laser light at 800 nm, the malignant cells are destroyed with half the energy to fatally affect the normal cells. This method may provide future diagnosis and therapy in one sitting [2]. Another example of the use of nanoparticles is described in a metaanalysis of studies using ferumoxtran-10, an ultrasmall superparamag-
netic iron oxide contrast agent for the detection of lymph-node metastases. The study controls were unenhanced magnetic resonance imaging (MRI) and histology. Overall sensitivity and specificity for nanoparticles was 0.88 and 0.96, respectively, compared with unenhanced MRI, which had sensitivity and specificity of 0.63 and 0.93, respectively. The authors concluded that iron-oxide-enhanced MRI had higher diagnostic precision than unenhanced MRI and allowed for the anatomic and functional definition of the disease [3]. A final example also of the use of iron oxide as a contrast agent is the magnetic labeling of migrating cells that are followed by MRI. Cell trafficking is an important component of systems biology and the future clinical use of stem and progenitor cells. Early studies in central nervous system disease models have demonstrated good spatial resolution and cell tracking over time. The authors of one study speculated that this method will be used in the foreseeable future to monitor cell therapy [4]. Support for nanotechnology is widespread at the National Institutes of Health and individual institutes and beyond. The National Cancer Institute developed the Centers of Cancer Nanotechnology Excellence. The program has been in effect for 7 years and has resulted in 8 centers, the newest of which is at the University of California, San Diego [5]. The National Institutes of Health Roadmap for Medical Research is another source of support for nanotechnology, with the Nanomedicine Roadmap Initiative. The goal of this initiative is to describe biomolecular systems in
© 2006 American College of Radiology 0091-2182/06/$32.00 ● DOI 10.1016/j.jacr.2006.05.004
Heard on the Campus 579
systems engineering terms, the endpoint of which is to create blueprints for nanomachines and structures to manipulate the systems for disease treatment and the repair of damaged cells and tissues [6]. Governmental support is not the only source of interest in nanotechnology for imaging. GE’s Global Research Center is involved in long-range nanotechnology nanoparticles. How can we as radiologists contribute to the various efforts in the development of our specialty? Learning about and developing a
practice of molecular imaging is one step. Supporting efforts by radiology societies such as the ACR and the Radiological Society of North America also are important steps. Only we can ensure our future in the new imaging environment. REFERENCES 1. National Science Foundation. Nanotechnology definition (NSET, February 2000). Available at: http://www.nsf.gov/crssprgm/ nano/reports/omb_nifty50.jsp. 2. Huang X, El-Sayed IH, Qian W, El-Sayed MA. Cancer cell imaging and photothermal
therapy in the near-infrared region by using gold nanorods. J Am Chem Soc 2006;128:2115-20. 3. Will O, Purkayastha S, Chan C, et al. Diagnostic precision of nanoparticle-enhanced MRI for lymph node metastases: a meta-analysis. Lancet Oncol 2006;7:52-60. 4. Bulte JW, Kraitchman, DL. Monitoring cell therapy using iron oxide MR contrast agents. Curr Pharm Biotechnol 2005;5:567-84. 5. National Cancer Institute. Centers of Cancer Nanotechnology Excellence (CCNEs). Available at: http://nano.cancer.gov/programs/ ccne_overview.asp. 6. National Institutes of Health, Office of Portfolio Analysis and Strategic Initiatives. Nanomedicine: overview. Available at: http:// nihroadmap.nih.gov/nanomedicine/.
Donald P. Harrington, MD, MA, University Hospital, Department of Radiology, Health Sciences Center, Level 4, Room 120, Stony Brook, NY 11794-8460; e-mail: [email protected]; Institute of Biomedical Imaging and Bioengineering, 6707 Democracy Boulevard, Suite 202, MSC-5477, Bethesda, MD 20892; Columbia Presbyterian Medical Center, Informatics, Vanderbilt Clinic 543, 622 West 168th Street, New York, NY 10032. This column was written in a personal capacity and does not represent the opinions of the National Institutes of Health, the US Department of Health and Human Services, or the Federal Government.