by Scott Haller, MS
The advancement and incorporation of novel technologies into the development of breakthrough medicines is an exciting reality of contemporary science. The application of molecular imaging in drug development is a great example. This evolving discipline is providing new insights into the biological effects of future therapeutics.
Today’s imaging systems allow for non-invasive, in vivo investigation of cellular and molecular events involved in normal and pathologic processes. Positron Emission Tomography (PET) and Single-Photon Emission Computed Tomography (SPECT) imaging can be used to generate 3-dimensional images to evaluate distribution, target engagement or efficacy of radiolabeled test material in tissues, and to intact biological systems. These technologies touch the full spectrum of drug development, from target identification, candidate selection/screening, and preclinical testing, to Phase I-III clinical study and post-marketing approval support.
Molecular imaging can be effectively integrated into development programs with various study designs to provide rich data sets to support the primary objective of the development program or specific therapeutic indication of interest. Selection of isotopes and imaging platforms is driven primarily by the chemical structure of the compound of interest and minimizing signal-to-noise or signal-to-background interference in the acquisition of the imaging data. Additional study design details, such as appropriate animal model, imaging acquisition protocols, and others, are defined by the therapeutic indication of interest.
Scientists also commonly design studies with the the intention of increasing overall resolution in the total data set by including both in vivo and ex vivo imaging in the final study design. Qualitative whole-body autoradiography (QWBA), involving the use of short- or long-lived radioisotopes, can be used to create a whole-body image showing tissue distribution of a tagged compound with greater resolution than that obtainable through PET or SPECT imaging alone. Other imaging tools and related processes, such as integrated small animal microPET/CT and microSPECT/CT, respiratory and cardiac-gated imaging, comprehensive data analysis and interpretation, and real-time determination of pharmacokinetics and pharmacodynamics are also commonly integrated into an appropriate imaging solution for development programs.
The value of molecular imaging is evident when one evaluates the varying applications of the technology throughout drug development. A few brief examples include
- Drug kinetics and biodistribution through whole-body imaging
- Studying tumor models and antibodies in cancer research
- Imaging cardiac function and apoptosis in cardiotoxicity assessment
- Brain imaging and mapping
A more recent advancement in the field of ex vivo imaging is the 3-dimensional rendering of optical white light images captured during the processing of standard QWBA sample block sectioning. Incorporation of images generated via differing imaging modalities (autoradiography, immunohistochemistry, fluorescent, etc.,) are then reconstructed into the 3-dimensional white light rendering, providing quantifiable data sets. This provides a bridge between in vivo imaging (macro resolution) and histological/pathological evaluation (micro resolution).
All of these innovative molecular imaging techniques continue to show new insights into drug development programs. Drug developers now have access to these capabilities to determine the effectiveness of their compound early on, allowing them to make go/no-go decisions earlier in their drug development programs, saving them time and money.
Scott Haller is Director of the Translational Imaging Center at MPI Research. He gave a presentation on molecular imaging at the recent Society of Toxicology Annual Meeting. To find out more about our Translational Imaging Center and our molecular imaging capabilities, contact us at email@example.com.