Kanekal S, Sahai A, Jones R E, Brown D
Matrix Pharmaceutical Inc., Menlo Park, California 94025, USA.
J Pharmacol Toxicol Methods. 1995 Jun;33(3):171-8. doi: 10.1016/1056-8719(94)00089-m.
This study evaluates a storage-phosphor imaging system for rapid autoradiography and quantitation of beta- and gamma-ray emitters in mice. Known quantities of authentic 3H, 14C, and 195mPt (0.06 to 31,714 DPM/mm2) were exposed to imaging plates of the storage-phosphor system for 0.5 min to 15 hr at room temperature. Immediately after exposure, the imaging plates were scanned and the autoradiograms were quantified. Radioactivity as low as 1.8 DPM/mm2 (3H), 0.06 DPM/mm2 (14C) and 3.1 DPM/mm2 (195mPt) was visualized and quantified in 8 hr (3H and 14C) and 6 min (195mPt), respectively. The system displayed a linear range of four to five orders of magnitude (14C: 0.5 to 6,914 DPM/mm2 for 2-hr exposure; 3H: 1.8 to 15,372 DPM/mm2 for 15-hr exposure; and 195mPt: 66 to 198,000 DPM 6 min-exposure). Variation from scan-to-scan was small (< 1% to 5%) and was more pronounced at the lower detection limits and exposure periods. Similar sensitivity, linearity, and variability were obtained in cryosections of murine tumors treated with 14C-fluorouracil or 3H-epinephrine and whole-body autoradiograms of mice treated with 195mPt-cisplatin via liver. The high sensitivity allowed noninvasive imaging of live unanesthetized mice treated with 195mPt with a short exposure time (105 sec). These results validate, for the first time, the high sensitivity, linearity, and wide dynamic range of storage-phosphor technology for quantitative autoradiography of 14C, 3H, and 195mPt isotopes. Storage-phosphor imaging will be useful in rapid quantitative autoradiographic disposition studies of radiolabeled drugs and excipients in vitro and in vivo.
本研究评估了一种用于小鼠β射线和γ射线发射体快速放射自显影及定量分析的存储磷光成像系统。将已知量的纯3H、14C和195mPt(0.06至31,714 DPM/mm2)在室温下暴露于存储磷光系统的成像板上0.5分钟至15小时。暴露后立即扫描成像板并对放射自显影片进行定量分析。分别在8小时(3H和14C)和6分钟(195mPt)内观察并定量分析了低至1.8 DPM/mm2(3H)、0.06 DPM/mm2(14C)和3.1 DPM/mm2(195mPt)的放射性。该系统显示出四到五个数量级的线性范围(14C:2小时暴露时为0.5至6,914 DPM/mm2;3H:15小时暴露时为1.8至15,372 DPM/mm2;195mPt:6分钟暴露时为66至198,000 DPM)。每次扫描之间的变化很小(<1%至5%),并且在较低检测限和暴露时间时更为明显。在用14C - 氟尿嘧啶或3H - 肾上腺素处理的小鼠肿瘤冷冻切片以及经肝脏用195mPt - 顺铂处理的小鼠全身放射自显影片中,获得了相似的灵敏度、线性度和变异性。高灵敏度使得在短暴露时间(105秒)下对用195mPt处理的未麻醉活小鼠进行无创成像成为可能。这些结果首次验证了存储磷光技术在14C、3H和195mPt同位素定量放射自显影方面的高灵敏度、线性度和宽动态范围。存储磷光成像将有助于在体外和体内对放射性标记药物和辅料进行快速定量放射自显影处置研究。