Medical Physics Seminar – Monday, March 12, 2012
PET Imaging & Radionclide Therapy with Cu-ATSM in Relation to Cancer Stem Cells
DR. Yasuhisa Fujibayashi, Ph.D., D.Med.Sci (guest of Dr. R. Jerry Nickles)
Director, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Emeritus Professor, Faculty of Medicine, University of Fukui, JAPAN
CAMERON LECTURER
We developed radioactive Cu-ATSM as a “hypoxic metabolism†seeking agent, reflecting abnormally reduced state of electron transport system in tumor cells, most probably caused under hypoxic conditions. Recently, various types of tissue stem cells have been reported, including cancer stem cells. Interestingly, stem cells prefer hypoxic conditions, and tumor cells in high Cu-ATSM regions showed similar characteristics as stem cells, such as low proliferation rate, hypoxia tolerant, drug resistant, and so on.
Thus, we performed immunohistochemical staining of CD-133, known as a stem cell marker in some tissues as well as Colon-26 cancer tissues. In the Colon-26 cancer tissues, % CD133 positive cells was higher in high Cu-ATSM region than low Cu-ATSM region (1 % vs. 0.1 %). From this finding, Cu-ATSM might have an ability to accumulate in stem cell-rich region.
Cu-ATSM has been reported as a selective drug delivery system (DDS) of therapeutic Cu-64 into radiation tolerant hypoxic tumor regions. When Cu-64-ATSM (1 mCi) was intravenously injected into tumor bearing mice, the tumor size was significantly reduced. In the treated tumor masses, % CD133 positive cells was lower than those of untreated tumor masses, indicating cancer cell selective therapeutic effect of internal radiation therapy using Cu-64-ATSM. Interestingly, intravenous injection of the isolated free tumor cells obtained from the treated tumors showed less metastasis formation in the lung. Similar findings were also obtained in in-vitro colony formation assay.
Cu-ATSM has a possibility to visualize a region of “hypoxic metabolism†in tumor mass which might contain tumor stem cell-rich region. And, Cu-64-ATSM could be a first selective therapeutic agent targeting cancer stem cell-rich region.
Originally, Cu-ATSM was simply designed for the diagnosis of hypoxic tumor. However, intensive research on its retention mechanism and characteristics of tumors brought us a new era of molecular imaging /therapy targeting cancer stem cells. Molecular imaging research is not only the unidirectional application of basic molecular biology to clinical medicine, but bidirectional cooperation between basic and practical life science fields.