肿瘤显像药物~(18)F-FLT的制备及其在早期肺癌与炎症鉴别中的应用研究
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摘要
目的早期肺癌与炎症的鉴别一直是困扰临床的一大难题,目前常用的反映糖代谢的显像药物~(18)F-FDG难以满足临床需求。本研究拟合成反映肿瘤增殖的显像药物~(18)F-FLT,用于早期肺癌与炎症的鉴别诊断。方法以3-N-t-叔丁氧羰基-1-[5’-O-(4,4’-二甲氧基三苯甲基)-2’-脱氧-3’-O-(4-硝基苯磺酰基)-β-D-苏型-呋喃戊糖基]胸苷为前体,通过Tracerlab FXN Pro合成模块自动化合成~(18)F-FLT并进行完整的质量控制。筛选5例早期肺癌患者进行~(18)F-FLT和~(18)F-FDG的对比显像。结果 ~(18)F-FLT放化产率为(12.2±1.5)%(n=5),纯度>99%,其它质控项目均满足临床要求。PET显像结果显示,有3例患者~(18)F-FLT和~(18)F-FDG显像结果一致,2例患者显像结果有显著差异,活检病理证实~(18)F-FLT对肺癌组织显像,而对炎症不敏感。结论本研究合成的~(18)F-FLT质量符合放射性药物注射要求,并具有鉴别早期肺癌和炎症的临床价值。
Objective It's difficult to differentiate early lung cancer and inflammation in clinical practice but ~(18)F-FDG cannot meet the clinical needs now. This study intends to synthesize ~(18)F-FLT, a tumor proliferation imaging drug, to research its potential in differentiating early lung cancer and inflammation. Methods In this study,(5'-O-DMTr-2'-deoxy-3'-O-nosyl-β-D-threo-pentofuranosyl)-3-N-BOCthymine was used as the precursor, and ~(18)F-FLT was synthesized automatically by Tracerlab FXN Pro synthesis module. After quality control was carried out, 5 early lung cancer patients were screened out for ~(18)F-FLT and ~(18)F-FDG PET imaging contrast. Results The radiochemical yield of ~(18)F-FLT was(12.2±1.5, n=5) %, and the radiochemical purity was more than 99%. Comparing the ~(18)F-FLT and ~(18)F-FDG PET images, the imaging results of 3 patients were coincident but different of 2 patients. Moreover, pathology results confirmed that ~(18)F-FLT was sensitive to early lung cancer, but not sensitive to inflammation. Conclusion ~(18)F-FLT was synthesized successfully. It has the potential of distinguishing early lung cancer from inflammation.
Objective It's difficult to differentiate early lung cancer and inflammation in clinical practice but ~(18)F-FDG cannot meet the clinical needs now. This study intends to synthesize ~(18)F-FLT, a tumor proliferation imaging drug, to research its potential in differentiating early lung cancer and inflammation. Methods In this study,(5'-O-DMTr-2'-deoxy-3'-O-nosyl-β-D-threo-pentofuranosyl)-3-N-BOCthymine was used as the precursor, and ~(18)F-FLT was synthesized automatically by Tracerlab FXN Pro synthesis module. After quality control was carried out, 5 early lung cancer patients were screened out for ~(18)F-FLT and ~(18)F-FDG PET imaging contrast. Results The radiochemical yield of ~(18)F-FLT was(12.2±1.5, n=5) %, and the radiochemical purity was more than 99%. Comparing the ~(18)F-FLT and ~(18)F-FDG PET images, the imaging results of 3 patients were coincident but different of 2 patients. Moreover, pathology results confirmed that ~(18)F-FLT was sensitive to early lung cancer, but not sensitive to inflammation. Conclusion ~(18)F-FLT was synthesized successfully. It has the potential of distinguishing early lung cancer from inflammation.
引文
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[3]Zhang Y, Zhao W, Zhang J. Comprehensive epigenetic analysis of the signature genes in lung adenocarcinoma[J]. Epigenomics, 2017, 9(9):1161-1173. doi:10.2217/epi-2017-0023.
[4]Humam K, Mohamed K, Wistuba II. Pulmonary adenocarcinoma:a renewed entity in 2011[J]. Respirology, 2012,17(1):50-65. doi:10.1111/j.1440-1843.2011.02095. x.
[5]Miller KD, Siegel R, Lin CC, et al. Cancer treatment and survivorship statistics, 2016[J]. CA Cancer J Clin, 2016,66(4):271-289. doi:10.3322/caac.21349.
[6]Wu HB, Wang L, Wang QS, et al. Adenocarcinoma with BAC features presented as the nonsolid nodule is prone to be false-negative on 18F-FDG PET/CT[J]. Biomed Res Int, 2015, 2015:243681. doi:10.1155/2015/243681.
[7]Visvikis D, Francis D, Mulligan R, et al. Comparison of methodologies for the in vivo assessment of 18FLT utilisation in colorectal cancer[J]. Eur J Nucl Med Mol Imaging,2004, 31(2):169-178. doi:10.1007/s00259-003-1339-2.
[8]Buck AK, Halter G, Schirrmeister H, et al. Imaging proliferation in lung tumors with PET:18F-FLT versus 18FFDG[J]. J Nucl Med, 2003, 44(9):1426-1431.
[9]Oh SJ, Mosdzianowski C, Chi DY, et al. Fully automated synthesis system of 3'-deoxy-3'-[18F]fluorothymidine[J]. Nucl Med Biol,2004, 31(6):803-809. doi:10.1016/j. nucmedbio.2004.01.008.