The imaging continuum: bench to biomarkers to diagnostics

Abstract

Innovation in basic and applied science has brought radiotracers to fruition as diagnostics. Non-invasive, longitudinal, and quantifiable molecular imaging is the key to diagnosing and monitoring numerous illnesses, with more to come from characterization of the clinical relevance of findings from genomics research. Radiotracers enable real-time in vivo studies of the effects of drug candidates on receptors, pathways, pharmacodynamics, and clinically relevant endpoints, thereby providing both early detection of pathophysiology to enable early intervention, and then monitoring of treatment responses to enable individualization of treatment regimens. We review developments which have translated imaging from 'bench to bedside', or 'biomarkers to diagnostics'. Notable developments include (1) synthesis methods for rapid 11 C labeling of biomolecules to high specific radioactivity; (2) ligand-binding assays for screening molecular imaging agents rather than drugs; (3) in vivo imaging of radiotracers in animals; (4) discovering the imaging advantages of 99m Tc, 11 C, and 18 F; (5) co-registration and automated quantitative assessment of high spatial resolution CT and MR images with molecular images from PET for longitudinal studies of treatment effect.

Is Subcutaneous Route an Alternative to Intravenous Route for Mouse Contrast-Enhanced Magnetic Resonance Imaging at 1.5 T?

“…Multimodal imaging continues to gain popularity in small animal preclinical research, not only because it satisfies the 3Rs principles (reduction, refinement, and replacement) [1][2][3], but also because it becomes a fundamental tool of translational medicine. In order to maximize translation from mouse to man, it is highly recommended to share common tomographic imaging procedures like single photon emission computed tomography (SPECT), positron emission tomography (PET), X-Ray Computed Tomography (CT), and nuclear magnetic resonance imaging (MRI) data acquisitions [4][5][6]. As in clinic, contrast agents for CT and MRI are needed in preclinical imaging in order to enhance tissues, organs, vessels, and lesions, and a considerable amount of laboratory engineering effort has been devoted in recent years to that purpose in order to develop specific MRI contrast agents [7][8][9].…”

“…As in clinic, contrast agents for CT and MRI are needed in preclinical imaging in order to enhance tissues, organs, vessels, and lesions, and a considerable amount of laboratory engineering effort has been devoted in recent years to that purpose in order to develop specific MRI contrast agents [7][8][9]. For all that, standard clinical contrast agents [10] are also widely used in preclinical MRI: they are typically smallmolecular-weight compounds that distribute nonspecifically 2 Concepts in Magnetic Resonance Part A in the blood plasma and extracellular space of the body after administration [4]. These compounds have the advantage of being low-cost than specific products and their use perfectly meets translational expectations.…”

Molecular Imaging in Cancer Drug Development

“…29,30 In spite of these difficulties, imaging has emerged as a powerful translational tool for proof-ofconcept and mechanistic studies in preclinical and clinical drug development within virtually every drug class. 2,[9][10][11][12][13] Molecular imaging in predictive animal models may provide a needed shift in the paradigm of drug discovery and development to transform the available pool of targets and new chemical entities into marketable drugs. 26,31 A desired property of preclinical imaging agents in drug development is that they should be easily translatable from the laboratory into established clinical nuclear medicine practices.…”

50th anniversary special issue, in memoriam John Jones

“…Kitson 1 talks about the development of The Radiochemical Centre in Amersham, UK, about what it is today as a part of GE Healthcare a major producer of isotopes and isotopically labelled compounds. 1 Frank et al 2 review the domain of imaging, which is of particular interest to GE Healthcare today. 2 Heys 3 surveys the developments in the use of organoiridium complexes for use in hydrogen exchange labelling techniques that have increased in importance because of the need for rapid methods for the labelling of compounds with the hydrogen isotopes deuterium and tritium.…”

“…1 Frank et al 2 review the domain of imaging, which is of particular interest to GE Healthcare today. 2 Heys 3 surveys the developments in the use of organoiridium complexes for use in hydrogen exchange labelling techniques that have increased in importance because of the need for rapid methods for the labelling of compounds with the hydrogen isotopes deuterium and tritium. 3 Lockley 4 continues with a similar theme of ortho-directed hydrogen isotope exchange labelling.…”