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Pre-clinical Study of 213Bi Labeled PAI2 for the Control of Micrometastatic Pancreatic Cancer

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Abstract

Purpose: The urokinase plasminogen activator (uPA) and its receptor (uPAR) are expressed by pancreatic cancer cells and can be targeted by the plasminogen activator inhibitor type 2 (PAI2). We have labeled PAI2 with 213Bi to form the alpha conjugate (AC), and have studied its in vitro cytotoxicity and in vivo efficacy.

Methods and Materials: The expression of uPA/uPAR on pancreatic cell lines, human pancreatic cancer tissues, lymph node metastases, and mouse xenografts were detected by immunohistochemistry, confocal microscopy, and flow cytometry. Cytotoxicity was assessed by the MTS and TUNEL assay. At 2 days post-cancer cell subcutaneous inoculation, mice were injected with AC by local or systemic injection.

Results: uPA/uPAR is strongly expressed on pancreatic cancer cell lines and cancer tissues. The AC can target and kill cancer cells in vitro in a concentration-dependent fashion. Some 90% of TUNEL positive cells were found after incubation with 1.2 MBq/ml of AC. A single local injection of ~222 MBq/kg 2 days post-cell inoculation can completely inhibit tumor growth over 12 weeks, and an intraperitoneal injection of 111 MBq/kg causes significant tumor growth delay.

Conclusions: 213Bi-PAI2 can specifically target pancreatic cancer cells in vitro and inhibit tumor growth in vivo. 213Bi-PAI2 may be a useful agent for the treatment of post-surgical pancreatic cancer patients with minimum residual disease.

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Authors and Affiliations

  1. Centre for Experimental Radiation Oncology, Cancer Care Centre, St George Hospital, Kogarah, NSW, Australia

    Chang F. Qu, Emma Y. Song, Yong Li, Syed M. A. Rizvi, Chand Raja & Barry J. Allen

  2. University of New South Wales, NSW, Australia

    Chang F. Qu, Emma Y. Song & Barry J. Allen

  3. Department of Surgery, Royal North Shore Hospital, NSW, Australia

    Ross Smith

  4. University of Sydney, NSW, Australia

    Ross Smith

  5. European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany

    Alfred Morgenstern & C. Apostolidis

  6. Centre for Experimental Radiation Oncology, Cancer Care Centre, St George Hospital, Gray st, Kogarah, NSW, 2217, Australia

    Barry J. Allen

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  1. Chang F. Qu
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  2. Emma Y. Song
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Correspondence to Barry J. Allen.

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Qu, C.F., Song, E.Y., Li, Y. et al. Pre-clinical Study of 213Bi Labeled PAI2 for the Control of Micrometastatic Pancreatic Cancer. Clin Exp Metastasis 22, 575–586 (2005). https://doi.org/10.1007/s10585-005-5788-9

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  • DOI: https://doi.org/10.1007/s10585-005-5788-9

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