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Preclinical imaging of prostate cancer using radiolabeled antibodies

Evans Axelsson, Susan LU (2013) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2013:149.
Abstract
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... (More)
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. (Less)
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author
supervisor
opponent
  • Professor Nilsson, Sten, Karolinska Institute, Department of Oncology-Pathology, Stockholm, Sweden
organization
publishing date
type
Thesis
publication status
published
subject
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2013:149
pages
58 pages
publisher
Division of Urological Cancers
defense location
Center for Molecular Pathology, Jan Waldenströms gata 59, Skåne University Hospital Malmö
defense date
2013-12-19 09:15
ISSN
1652-8220
ISBN
978-91-87651-24-3
language
English
LU publication?
yes
id
f0a3e204-91eb-4ba3-a540-ee35a6592603 (old id 4178770)
date added to LUP
2013-12-13 09:08:27
date last changed
2019-03-13 18:09:02
@phdthesis{f0a3e204-91eb-4ba3-a540-ee35a6592603,
  abstract     = {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. <br/><br>
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. <br/><br>
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. <br/><br>
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.},
  author       = {Evans Axelsson, Susan},
  isbn         = {978-91-87651-24-3},
  issn         = {1652-8220},
  language     = {eng},
  pages        = {58},
  publisher    = {Division of Urological Cancers},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Preclinical imaging of prostate cancer using radiolabeled antibodies},
  volume       = {2013:149},
  year         = {2013},
}