Department of Molecular Imaging, Medical Photonics Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan.
Ann Nucl Med. 2013 Aug;27(7):669-75. doi: 10.1007/s12149-013-0734-4. Epub 2013 May 12.
Our final goal is to develop an appropriate method using nuclear medicine technique for monitoring the effect and prediction of Photodynamic Therapy (PDT) on tumors. The aim of this study is to evaluate the effect of PDT on tumor cells in vitro using (18)F-FDG and (99m)Tc-MIBI as tracers.
Five tumor cell lines (A431, DU145, H1650, LS180, SHIN3) with varied characteristics were irradiated after incubating for 24 h with several doses of Photofrin (PF). Singlet oxygen was monitored by the near-IR emission detection system during irradiation and generated (1)O2 was calculated. PDT effects were rapidly evaluated by nuclear medicine techniques (uptake of (18)F-FDG and (99m)Tc-MIBI) and traditional methods for cell viability (MTT and trypan blue assays) at 3 h after PDT. Intracellular PF concentration was measured by absorption spectrometer and cell protein content was measured by the Lowry method. (18)F-FDG uptake, (99m)Tc-MIBI uptake, singlet oxygen, and intracellular PF concentration were standardized by protein content. Decrease % of (18)F-FDG and (99m)Tc-MIBI, MTT, and trypan blue was normalized to the control group.
Decrease % of (18)F-FDG was exponentially related to decrease % of MTT (R (2) = 0.650, P < 0.01) while decrease % of (99m)Tc-MIBI was linearly related to that of MTT (R (2) = 0.719, P < 0.01). The decrease % of MTT was more sensitive than that of trypan blue. However, neither (1)O2 nor PF uptake was correlated with sensitivity to PDT. In addition, (18)F-FDG uptake before PDT was linearly related to decrease % of MTT (R (2) = 0.800, P < 0.05).
Our findings in in vitro studies suggest that (99m)Tc-MIBI is better than (18)F-FDG for early evaluation of PDT effect, but (18)F-FDG uptake may be used to predict PDT sensitivity before therapy.
我们的最终目标是开发一种使用核医学技术监测光动力疗法(PDT)对肿瘤效果和预测的合适方法。本研究旨在使用(18)F-FDG 和(99m)Tc-MIBI 作为示踪剂,评估 PDT 对体外肿瘤细胞的影响。
将 5 种具有不同特征的肿瘤细胞系(A431、DU145、H1650、LS180、SHIN3)在孵育 24 小时后用不同剂量的血卟啉(PF)进行照射。在照射过程中,通过近红外发射检测系统监测单线态氧,并计算生成的(1)O2。PDT 效果在 PDT 后 3 小时通过核医学技术((18)F-FDG 和(99m)Tc-MIBI 的摄取)和传统细胞活力方法(MTT 和台盼蓝测定)快速评估。通过吸收光谱仪测量细胞内 PF 浓度,通过 Lowry 法测量细胞蛋白含量。(18)F-FDG 摄取、(99m)Tc-MIBI 摄取、单线态氧和细胞内 PF 浓度通过蛋白含量标准化。(18)F-FDG 和(99m)Tc-MIBI 的减少%、MTT 和台盼蓝减少%均归一化为对照组。
(18)F-FDG 的减少%与 MTT 的减少%呈指数关系(R 2=0.650,P<0.01),而(99m)Tc-MIBI 的减少%与 MTT 的减少%呈线性关系(R 2=0.719,P<0.01)。MTT 的减少%比台盼蓝更敏感。然而,(1)O2 或 PF 摄取均与 PDT 敏感性无关。此外,PDT 前(18)F-FDG 的摄取与 MTT 的减少%呈线性关系(R 2=0.800,P<0.05)。
我们在体外研究中的发现表明,(99m)Tc-MIBI 比(18)F-FDG 更适合早期评估 PDT 效果,但(18)F-FDG 摄取可能用于治疗前预测 PDT 敏感性。