Overview: Transforming in Vivo Diagnostics into a Molecular Measurement Science.
Authors: Michael Phelps
Journal: Clinical Cancer Research (2006)

PL-19   Various  in vivo molecular, functional and structural imaging technologies are being developed and applied to differential diagnosis, staging, assessment of therapeutic responses, and drug discovery and development processes, from preclinical to clinical, from PET to optical, MRI and CT. The information that the molecular and biological imaging technologies are seeking to provide are to image: 1) the biology and biochemistry of disease to provide molecular diagnostics for research and patient care. 2) the disease/drug target to stratify subjects into those who have the target from those who do not. 3) biological processes involved with the disease/drug target for use as surrogate markers of disease to identify the presence of disease and its response to the drug , which will help separate responders from non-responders and match drugs to the stage of cancer in individual patients. 4) the pharmacokinetics and pharmacodynamics of drugs -- Did the drug hit the target? Did the drug occupy enough of the drug target to induce the desired pharmacologic effect? Where else did the drug go in the body over time? It is critical that these biomarkers, surrogate markers and pharmacokinetic and pharmaco dynamic approaches develop as a measurement science and that measures developed and applied in preclinical settings be translatable to the patients for clinical research, guiding therapeutic trials and providing molecular diagnostics in patient care. This session will show some of the technological approaches and applications of PET and PET/CT, MRI and optical imaging to the questions listed above in cancer. For example, technologies are being developed to allow for the convenient translation of molecular imaging technologies into measurement devices with outputs of information desired in biological and pharmaceutical studies using systems like the Kinetic Imaging Software (KIS) that has been designed to be easy and fun to use. KIS has three domains: 1) Library to define the terminology and kinetic principles of molecular imaging probes and pharmacokinetics; 2) Simulation that contains compartmental models of biological systems with their mathematical engines, along with blood and tissue time activity curves with easy ways to change transport and reaction rate constants and display results in graphs and simulated whole body images as a function of time; and 3) Analysis that uses real data to extract tracer- and pharmaco-kinetic parameters and to develop biochemical and pharmacokinetic assays with molecular probes and drugs. While advances will continue to occur in imaging instrumentation, the greatest progress and impact are occurring, and will continue to occur, in the development of imaging biomarkers, biological assays and assays of drugs. New automated chemical synthesis technologies that employ conventional chemistry and in situ click chemistry in integrated microfluidics chips operated by a PC are being used to accelerate, simplify and diversify the types of molecular imaging probes produced. While many of the goals above can be realized today, there are others with technical and scientific hurdles to overcome in order to provide their benefits to biological and pharmacological sciences and the drug discovery and development processes, as well as the use of these developments in expanding   in vivo  molecular imaging diagnostics in the care of patients. It is reasonable and appropriate to integrate the goals and resources of molecular imaging diagnostics and therapeutics to each other9s benefit. In addition, it is important to integrate   in vitro  and   in vivo  molecular diagnostics into a systems biology view of disease - get the biology of disease right to guide molecular diagnostics.