Preclinical molecular imaging of target expression and target dynamics in cancer

Martin Pool

    Research output: ThesisThesis fully internal (DIV)

    154 Downloads (Pure)

    Abstract

    Molecular imaging is an attractive tool to non-invasively determine target protein presence and distribution, and the uptake and accessibility of novel anticancer drugs. Information gained from molecular imaging can aid drug development. Molecular imaging can furthermore be used to visualize informative molecular tumour characteristics for clinical decision-making.

    Several new molecular imaging ‘tracers’ were developed, scout doses of radioactive or fluorescently labeled drugs. Tracers were developed based upon novel drugs targeting EGFR, HER2, HER3, c-MET and EpCAM, receptors/proteins which are commonly dysregulated in human cancers. These tracers were employed to study the influence of molecular targeted cancer therapies and other factors on organ distribution and tumour uptake of these drugs using fluorescence and PET-scans, as well as microscopy.

    The EGFR-tracer was employed to study the effects of circulating EGFR protein in blood on the tumour uptake of an EGFR-directed therapeutic antibody. c-MET and HER3-directed tracers were used to visualize these receptors in response to, and resistance against molecular targeted therapeutic agents. Furthermore, the tumour uptake, organ distribution and macro- and microscopic drug distribution of a EpCAM-directed BiTE was studied. In addition, a fluorescent HER2-tracer was used to validate novel microscopic techniques.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • de Vries, Liesbeth, Supervisor
    • Lub-de Hooge, Marjolijn, Co-supervisor
    • Terwisscha Van Scheltinga, Antonius, Co-supervisor
    • Boerman, O. C., Assessment committee, External person
    • Huitema, A. D. R., Assessment committee, External person
    • Elsinga, Philip, Assessment committee
    Award date12-Apr-2017
    Place of Publication[Groningen]
    Publisher
    Publication statusPublished - 2017

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