Preclinical imaging of prostate cancer using radiolabeled antibodies
Sammanfattning: Target-specific molecular imaging with radiolabeled antibodies has experienced a rapid growth over the past 20 years, and is now an essential tool to provide information on disease presence and extent. Despite all efforts to detect and control prostate cancer at an early stage, a number of men are still progressing to develop incurable metastatic disease. Because of this, development of new methods based on target-specific imaging is becoming increasingly important in the assessment and management of prostate cancer. The main purpose of this work was to investigate three target antigens: Ku70/Ku80, free prostate specific antigen (fPSA) and ICAM-1, as potential candidates for imaging of prostate cancer using radiolabeled antibodies. The studies were designed to assess the in vivo and ex vivo tumor targeting potential using animal models of prostate cancer. Preclinical SPECT/CT and PET/CT in vivo imaging modalities, ex vivo multi-radionuclide digital autoradiography, ex vivo activity measurements and immunohistochemistry were used to obtain biokinetics and specific activity uptake. In these studies, we found that radiolabeled INCA-X mAb could efficiently target the Ku70/Ku80 antigen in prostate cancer xenografts in mice that first receive a predose of non-labeled antibody. We also demonstrate that two antibodies specific for fPSA (PSA30 and 5A10) can efficiently target PSA positive prostate cancer xenografts. In that study, we also show that the animal models immune deficiency status can affect the antibody performance. Lastly, we show that 111In-R6.5 mAb outperformed the 177Lu-R6.5 or control IgG mAb and can be used as a complement to clinically used metabolic and proliferative probes. Our ex vivo and in vivo investigations presented in this dissertation should act as support for further studies of the Ku70/Ku80, fPSA and ICAM-1 antigens. Future studies should include therapeutic applications based on dosimetry calculation to evaluate possible therapeutic efficacy.
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