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Assessment of DNA/RNA Deregulation in Cancer Using 99m Tc-Labeled Thiopurine.
Cancer Biotherapy & Radiopharmaceuticals 2024 March 9
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.
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