Introduction to concepts and strategies for molecular imaging.

Molecular imaging is a branch of medical imaging science that aims to detect, localize, and monitor critical molecular processes in cells, tissue, and living organisms using highly sensitive instrumentation and contrast mechanisms. This area of medical imaging has developed alongside the emergence of molecular medicine, in which the genetic makeup of each patient factors into treatment planning. Through the use of gene analysis, it is possible today to identify patients that are prone to specific diseases, and consequently, novel chemotherapeutics have been developed to target specific disease biomarkers. This treatment strategy spares healthy tissue and maximizes therapeutic efficacy of the drugs. Critical to the success of molecular medicine is molecular imaging, which is not confined to the traditional silos of imaging specialties such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission tomography (SPECT), positron emission tomography (PET), ultrasound imaging, and optical imaging methods. Instead, molecular imaging is a multidisciplinary endeavor that harnesses the expertise of diverse scientists, engineers, and clinicians. Chemists, in particular, play a critical role in this effort. They are continuously challenged to use innovative chemical strategies to develop smart imaging agents that can produce detectable signals that arise from low concentrations of target biomolecules in cells and tissue. The past 10 years have witnessed the evolution of molecular design to address the ever-changing and challenging needs of molecular imaging research. Most of the initial studies focused on cell studies, in which molecular imaging has unraveled the dynamics and functions of many biomolecules and molecular interactions using advanced microscopy techniques and diverse molecular probes. Translation of findings in cells to living organisms is the focus of many preclinical and clinical molecular imaging studies. There are several objectives of molecular imaging. These include early detection of disease, monitoring of drug efficacy and treatment response, patient stratification, and identification of disease susceptibility. In this issue of Chemical ReViews, leading experts in the field of molecular imaging examine the recent advances in their various fields of study, identify critical issues limiting progress, and suggest strategies to further advance the field. The articles focus on major imaging technologies that are used in molecular imaging. Those that are predominantly used to produce anatomical information such as CT are excluded. Extensive reviews related to bioluminescent and fluorescent proteins are available elsewhere and appear in some articles as part of a larger discussion on molecular imaging probes for optical imaging. Each imaging modality, as they are frequently called by imaging scientists, brings unique information to molecular imaging. Optical and nuclear imaging methods are the workhorse of in vivo molecular imaging because of their high detection sensitivity. Currently, only nuclear imaging is used in clinical settings. Although MRI is largely a functional and anatomical imaging method, novel contrast mechanisms and the heightened interest in magnetic resonance spectroscopy (MRS) are making it possible to extract molecular information from this modality. Other molecular sensing methods such as mass spectral imaging and electron paramagnetic resonance (EPR) methods are included with the hope that molecular imaging scientists will incorporate these technologies into their arsenal of imaging tools. The reviews are organized into different themes, starting with traditional optical, nuclear, and MRI/MRS methods, followed by multimodal and cross-modality strategies, concluding with EPR oximetry and mass spectrometry methods. Optical imaging can furnish images of cells and tissues at shallow depths with exceptionally high spatial resolution, but this resolution decreases rapidly as a function of the imaging depth. However, there is a clear path for the use of optical molecular imaging in humans. For example, oral, skin, cervical, and endoscope-accessible tissues are amenable to optical molecular imaging. Although many reports of the use of optical methods in human subjects are available, few such reports on molecular optical imaging have been documented. Nearly all the optical imaging methods reported in this thematic issue use a fluorescence signal for molecular imaging because of the high detection sensitivity of this imaging technique. A cell is the fundamental unit of living organisms, and we can apply information gleaned from molecular processes in cells to intact living organisms. It is therefore appropriate that Sinkeldam et al. lead off the issue by taking us on a journey through the cell. Starting with carbohydrates on the cell surface, through cell membranes and into the cytoplasm, the authors describe approaches and challenges of developing Samuel Achilefu is Professor of Radiology, Biomedical Engineering, Biochemistry and Molecular Biophysics, and the Director of Optical Radiology Lab at Washington University in St. Louis, Missouri, U.S.A. His research interests are in the design, development, and biochemical evaluation of molecular imaging agents and drugs in cells and living organisms. He utilizes optical and multimodal imaging platforms that include nuclear, ultrasound, and magnetic resonance imaging to study the molecular basis of diseases and monitor early response to treatment. He obtained a Ph.D. in Chemistry in 1991 at the University of Nancy, France, and completed his postdoctoral training in oxygen transport mechanisms and blood substitutes at Oxford University, England, between 1991 and 1993. Before joining Washington University School of Medicine in 2001, he served as Principal Investigator in the Discovery Research Department at Mallinckrodt Medical, Inc., where he led the liquid ventilation project and championed the optical molecular imaging program. He is the lead or coinventor on more than 40 U.S. patents covering his diverse interests in molecular imaging. He can be contacted at [email protected], (314) 362-8599 (Tel.), or (314) 747-5191 (Fax). Chem. Rev. 2010, 110, 2575–2578 2575