期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 24, 页码 -出版社
MDPI
DOI: 10.3390/ijms222413466
关键词
auger electron therapy; dosimetry; molecular radionuclide therapy; radiobiology; sodium iodide symporter; technetium; triple-negative breast cancer cells
资金
- EPSRC Centre for Doctoral Training in Medical Imaging [EP/L015226/1]
- Matt Wilson Research Enhancement Scholarship
- Cancer Research UK [C48390/A21153]
- MRC Doctoral Training Partnership [MR/N013700/1]
- Academy of Medical Sciences [SBF001\1019]
- EPSRC programme [EP/S032789/1]
- Wellcome Trust [WT203148/Z/16/Z]
- EPSRC [EP/S032789/1] Funding Source: UKRI
Auger electron-emitters are being studied as potential radionuclides for molecular radionuclide therapy, with technetium-99m widely used for imaging but not yet fully assessed for therapeutic use. This study used MDA-MB-231.hNIS-GFP cells to model cellular radionuclide uptake, leading to observations of DNA damage and reduced clonogenicity with [Tc-99m]TcO4-, providing guidance for the safe use of technetium-99m in imaging and potential therapeutic applications.
Auger electron-emitters increasingly attract attention as potential radionuclides for molecular radionuclide therapy in oncology. The radionuclide technetium-99m is widely used for imaging; however, its potential as a therapeutic radionuclide has not yet been fully assessed. We used MDA-MB-231 breast cancer cells engineered to express the human sodium iodide symporter-green fluorescent protein fusion reporter (hNIS-GFP; MDA-MB-231.hNIS-GFP) as a model for controlled cellular radionuclide uptake. Uptake, efflux, and subcellular location of the NIS radiotracer [Tc-99m]TcO4- were characterised to calculate the nuclear-absorbed dose using Medical Internal Radiation Dose formalism. Radiotoxicity was determined using clonogenic and gamma-H2AX assays. The daughter radionuclide technetium-99 or external beam irradiation therapy (EBRT) served as controls. [Tc-99m]TcO4- in vivo biodistribution in MDA-MB-231.hNIS-GFP tumour-bearing mice was determined by imaging and complemented by ex vivo tissue radioactivity analysis. [Tc-99m]TcO4- resulted in substantial DNA damage and reduction in the survival fraction (SF) following 24 h incubation in hNIS-expressing cells only. We found that 24,430 decays/cell (30 mBq/cell) were required to achieve SF0.37 (95%-confidence interval = [SF0.31; SF0.43]). Different approaches for determining the subcellular localisation of [Tc-99m]TcO4- led to SF0.37 nuclear-absorbed doses ranging from 0.33 to 11.7 Gy. In comparison, EBRT of MDA-MB-231.hNIS-GFP cells resulted in an SF0.37 of 2.59 Gy. In vivo retention of [Tc-99m]TcO4- after 24 h remained high at 28.0% +/- 4.5% of the administered activity/gram tissue in MDA-MB-231.hNIS-GFP tumours. [Tc-99m]TcO4- caused DNA damage and reduced clonogenicity in this model, but only when the radioisotope was taken up into the cells. This data guides the safe use of technetium-99m during imaging and potential future therapeutic applications.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据