What is Molecular Imaging
Molecular Imaging (MI) is a growing biomedical research discipline that enables the visualization, characterization, and quantification of biologic processes taking place at the cellular and subcellular levels within intact living subjects, including patients. MI images depict cellular and molecular pathways and mechanisms of disease present in the context of the living subject. Study of biologic processes in their own physiologically authentic environment is facilitated - MI transcends the requirements for and limitations of in vitro or ex vivo biopsy/cell culture laboratory techniques. It also encompasses 'multiple' image-capture techniques in combination with merging knowledge areas from the fields of cell/molecular biology, chemistry, pharmacology, medical physics, biomathematics, and bioinformatics.
Modern clinical scientist researchers use MI to study the processes of how molecular abnormalities, found in cells, build up to form the basis of disease. This type of study in turn facilitates other important clinical goals of 1) early detection of disease 2) optimizing therapies that aim for certain molecular targets 3) predicting and monitoring response to therapy and 4) monitoring for disease recurrence. Biotechnology companies also use MI to optimize the drug discovery and validation processes.
In stark contrast to classical imaging that details end-stage gross pathology/anatomy, MI reveals, within a living subject, the underlying biology occurring deep within cells anywhere in the body - this adds functional to anatomic information that is then available to clinical researchers and increases both our understanding about disease and our ability to intervene with treatment at an earlier time.
The Nuts and Bolts
The science of the Molecular Imaging process, or ‘research chain’, that starts with a biological target of interest and spans to the actual imaging of a living subject is both complex and multi-faceted. This chain is fundamental to the field and critical for its success. Not all MI research is intended for clinical translation. In some cases, MI assay development progresses only to the computer modeling stage.
The Molecular Imaging Program at Stanford (MIPS) currently houses 26 different laboratories comprising 6 broad sections of MI technology and assay development in: Chemistry, Cell biology, Instrumentation, Pre-Clinical, Clinical, and Nanotechnology. Within these MIPS laboratories, considerable research efforts are focused toward 5 key research areas that include:
- synthesis and validation of radiolableled and fluorescent molecular probes for moelcular imaging.
- development of MI instrumentation for living subjects.
- development of MI approaches/assays for interrogating cellular events in living subjects.
- development of software tools for visualization and analysis of MI data.
- merger of therapeutics and imaging strategies for improved patient management.
Molecular Imaging originates in the field of nuclear medicine, and has now developed to include an array of different strategies to produce imaging signals. Where nuclear medicine uses radiolabeled molecules (tracers) that produce signals from radioactive decay only, MI uses these and other molecules to image via sound (ultrasound), magnetism (MRI or magnetic resonance imaging), or light (optical techniques of bioluminescence and fluorescence) as well as other emerg- ing techniques e.g. photoacoustic imaging, raman spectroscopy, and amide proton transfer Imaging.
MI's founding principles are rooted in nuclear medicine procedures of the past few decades, whereas the adaptation/ inclusion of 'other' technologies has occurred more recently through the development of different types of molecular probes. These probes are classified at the widest level as: nonspecific or specific. Nuclear medicine plays a key role in the latter class, serving as the signaling portion of specifically targeted probes. Probes that incorporate antibodies, ligands, or substrates to specifically interact with protein targets in particular cells or subcellular compartments comprise those used in most conventional radiotracer imaging methods - here the emphasis lies in imaging final products of gene expression with radiolabeled substrates that interact with a protein originating from a specific gene. These interactions are based on either receptor-radioligand binding, or enzyme mediated trapping of a radiolabeled substrate.
Due to the difficulties of 'specific' approaches (i.e. constructing a different probe for each newfound target and then characterizing that probe in vivo), the development of 'generalizable' methods (i.e. those that can image gene product targets arising from the expression of any gene of interest) has been inspired. This has further propelled the more recent development and validation of MI reporter gene/reporter probe systems for use in living subjects together with other generalizable strategies.
History of Molecular Imaging and MIPS
Molecular Imaging: As a field, Molecular Imaging dates back to the mid-1990’s for the start of its broad development. This start was enabled by a combination of factors - significant advances in molecular/cell biology techniques, new methods of combinatorial drug design, high-throughput testing, and the notable emergence of novel imaging techniques and probes. Additionally, significant funding for the MI field became available from the NIH, and other agencies, in the late 1990’s.
MIPS: MIPS was established as an inter-disciplinary program in 2003 by the Dean of the School of Medicine (Dr. Philip Pizzo) to bring together scientists and physicians who share a common interest in developing and using state-of-the-art imaging technology and developing MI assays for studying intact biological systems. The program, since its inception, has been steadily directed by Dr. Sanjiv Sam Gambhir, Virginia & D.K. Ludwig Professor of Cancer Research and Chair of Ra- diology, and co-directed by Dr. Christopher Contag, Professor of Pediatrics, and of Microbiology and Immunology and by courtesy, of Radiology. MIPS has fostered a multimodality approach that uses imaging technologies such as positron emission tomography (PET), single photon emission computed tomography (SPECT), digital autoradiography, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), optical bioluminescence, optical fluorescence, ultra- sound, and other emerging ones, where all technologies are under active development and investigation. The founding and continuing goals of the MIPS program remain: i) to fundamentally change how biological research is performed with cells in their intact environment in living subjects, and ii) to develop new ways to diagnose diseases and monitor therapies in patients. Areas of active investigation span cancer research, microbiology/immunology, developmental biology and pharmacology.
Since joining Stanford in 2003 to guide MIPS, Dr. Gambhir, together with Dr. Contag, has overseen the building of a leading program in MI that has developed unique collaborations and interactions across both Stanford and the nation. Dr. Gambhir also designed and opened in late 2010 the new Nuclear Medicine & Molecular Imaging Clinic that brings state-of-the-art clinical care to adult and pediatric patients. Funding for MIPS research activities comes from a mix of Federal (National Institutes of Health and Department of Energy), Foundation, and University sources, as well as through a number of collaborations with Industry.