Assessment of DNA/RNA Deregulation in Cancer Using 99m Tc-Labeled Thiopurine.
- Resource Type
- Academic Journal
- Authors
- Chiu CH; Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.; Yang DJ; Seecure/Taiwan Hopax Chemicals MFG Company Ltd., Kaohsiung, Taiwan.; Liou YC; Institute of Neuroscience, National Chaio Tung University, Taipei, Taiwan.; Chang WC; Seecure/Taiwan Hopax Chemicals MFG Company Ltd., Kaohsiung, Taiwan.; Yu TH; Brain Research Center, National Chaio Tung University, Taipei, Taiwan.; Brain Research Center, School of Medicine, National Defense Medical Center Taipei, Taiwan.; Chung MC; Seecure/Taiwan Hopax Chemicals MFG Company Ltd., Kaohsiung, Taiwan.; Lee YC; Seecure/Taiwan Hopax Chemicals MFG Company Ltd., Kaohsiung, Taiwan.; Chen IJ; Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.; Wang PY; Brain Research Center, School of Medicine, National Defense Medical Center Taipei, Taiwan.; Lin CP; Institute of Neuroscience, National Chaio Tung University, Taipei, Taiwan.; Tsay HJ; Institute of Neuroscience, National Chaio Tung University, Taipei, Taiwan.; Yeh SH; Brain Research Center, National Chaio Tung University, Taipei, Taiwan.; Brain Research Center, School of Medicine, National Defense Medical Center Taipei, Taiwan.
- Source
- Publisher: Mary Ann Liebert, Inc Country of Publication: United States NLM ID: 9605408 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-8852 (Electronic) Linking ISSN: 10849785 NLM ISO Abbreviation: Cancer Biother Radiopharm Subsets: MEDLINE
- Subject
- Language
- English
Background: DNA biomarkers are useful for the assessment of tumor cell proliferation. The authors aimed to synthesize a thiopurine-based ligand for evaluation of nuclear uptake and tumor localization. Materials and Methods: A 2-hydroxypropyl spacer was incorporated between a chelator (cyclam) and thiopurine ligand to produce SC-06-L1. In vitro cellular uptake and the cell/media ratios of [ 99m Tc]Tc-SC-06-L1 were assessed in breast (MCF-7, MDA-MB-231) and ovarian (TOV-112D, OVCAR3) cancer cells. The nuclear and cytosolic uptake ratio of [ 99m Tc]Tc-SC-06-L1 was determined in OVCAR-3 and MCF-7 cells. Cytotoxicity assays and flow cytometric analysis of cell cycle apoptosis were conducted in cancer cells treated with SC-06-L1. Imaging was conducted in tumor-bearing mice; fluorine-18-2'-fluorodeoxyglucose ([ 18 F]FDG) was used as a control. Results: The radiochemical purity of [ 99m Tc]Tc-SC-06-L1 was >95%. [ 99m Tc]Tc-SC-06-L1 exhibited higher cell-to-media ratios than [ 18 F]FDG in cancer cells. [ 99m Tc]Tc-SC-06-L1 had high uptake in the nuclear fractions in OVCAR-3 and MCF-7 cells, with nuclear/cytosolic ratios of 8 and 2, respectively. Cytotoxicity assays showed that SC-06-L1 was non-toxic compared with azathioprine in breast and ovarian cancer cells. Conclusions: [ 99m Tc]Tc-SC-06-L1 was stable and involved in nuclear activities. [ 99m Tc]Tc-SC-06-L1 showed non-toxic to cancer cells and exhibited fast kinetic uptake patterns for tumor imaging. [ 99m Tc]Tc-SC-06-L1 represents a promising biomarker for imaging purine pathway-directed systems.