The Gastrin-Releasing Peptide Receptor as Target for Molecular Imaging of Prostate Cancer: GRPR expression in prostate cancer and targeting with Bombesin-like radiopharmaceuticals

Hildo Ananias

    Research output: ThesisThesis fully internal (DIV)

    622 Downloads (Pure)

    Abstract

    Worldwide, prostate cancer (PCa) is a frequent cause of cancer, morbidity and death. Accurate staging poses several dilemmas and is still suboptimal. The Gastrin-Releasing Peptide Receptor (GRPR) is a tumor-associated antigen overexpressed in PCa. Targeted imaging of GRPR with nuclear imaging techniques can be achieved by using radiolabeled bombesin analogues. In this dissertation an overview is provided of the clinical and preclinical research performed on PCa imaging with radiolabeled bombesin analogues. Furthermore the expression of GRPR and several other target antigens in PCa metastases and post-radiotherapy locally recurrent PCa was determined by immunohistochemical staining of human tissue specimens. GRPR appeared to be expressed in 85.7% of lymph node metastases and in 52.9% of bone metastases of PCa. Although expression of GRPR was observed in 100% of locally recurrent PCa tissue samples, the tumor distinctiveness of GRPR in irradiated recurrent PCa was nil due to equal GRPR staining of benign stroma.
    Also two new bombesin-based radiopharmaceuticals, 99mTc-HYNIC(tricine/TPPTS)-Aca-Bombesin(7-14) and the homodimer 111In-DOTA-[Aca-Bombesin (7-14)]2, were investigated for their tumor targeting properties in PCa xenograft mouse models. Both compounds demonstrated good and specific tumor uptake, combined with high stability in human serum and high tumor-to-background contrast. Based on these results 99mTc-HYNIC(tricine/TPPTS)-Aca-Bombesin(7-14) was also evaluated with SPECT/CT in eight patients with proven disease. No uptake in the prostate was observed due to poor in vivo stability of the radiopharmaceutical. This finding is conflicting with the excellent results of the preclinical in vitro stability test in human serum performed previously and warrants further research.
    Translated title of the contributionDe Gastrin-Releasing Peptide Receptor as doel voor Moleculaire Beeldvorming van prostaatkanker: GRPR expressie in prostaatkanker en beeldvorming met bombesine-achtige radiofarmaca
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • de Jong, Igle Jan, Supervisor
    • Elsinga, Philip, Supervisor
    • Dierckx, Rudi, Supervisor
    Award date15-Oct-2014
    Place of Publication[S.l.]
    Publisher
    Print ISBNs978-90-367-7103-0
    Electronic ISBNs978-90-367-7102-3
    Publication statusPublished - 2014

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