Bae Soo-Jin, Lee Dae-Sic, Berezin Vladimir, Kang Uk, Lee Keun-Ho
Korea Electrotechnology Research Institute, Seoul, Korea.
Department of Obstetrics and Gynecology, Catholic Research Institutes of Medical Science, The Catholic University of Korea, Seoul, Korea.
J Obstet Gynaecol Res. 2016 Dec;42(12):1846-1853. doi: 10.1111/jog.13101. Epub 2016 Oct 17.
The aim of this study was to develop a novel optical imaging system for detecting protoporphyrin IX (PpIX) autofluorescence, to prove that PpIX autofluorescence is as useful as 5-aminolevulinic acid (5-ALA)-induced fluorescence for detecting and localizing cervical cancer, and to monitor the change in PpIX autofluorescence or induced PpIX fluorescence before, during, and after photodynamic therapy (PDT).
TC-1 cells - highly tumorigenic cells immortalized using human papillomavirus type 16 proteins E6 and E7 - were subcutaneously grafted into the thighs of nude mice. The suspected tumor tissues were visualized using autofluorescence imaging and induced fluorescence imaging under 5-ALA administration. When the 5-ALA-induced PpIX was sufficiently accumulated in tumor tissues, PDT was performed using a 635-nm laser. We observed the change in fluorescence intensity during PDT. For 3 weeks after PDT, we monitored tumor remission by using white-light imaging and fluorescence imaging.
The transplanted cells were visualized by PpIX autofluorescence, which was induced by heme synthesis. After 5-ALA administration, PpIX could be targeted by using PDT, which decreased PpIX autofluorescence. Photobleaching is useful for monitoring PDT dosimetry and for determining the photodynamic response to therapy.
PpIX autofluorescence clearly differentiated the tumor from adjacent normal tissues. The results of PpIX autofluorescence imaging and 5-ALA-induced fluorescence imaging were identical. PpIX autofluorescence imaging is a simple and cost-effective cervical cancer screening method that could be performed during or after PDT to ensure effective treatment or remission as a change in fluorescence intensity can be observed in real time without a blinding effect.
本研究旨在开发一种用于检测原卟啉IX（PpIX）自体荧光的新型光学成像系统，以证明PpIX自体荧光在检测和定位宫颈癌方面与5-氨基酮戊酸（5-ALA）诱导的荧光同样有用，并监测光动力疗法（PDT）前、治疗期间和治疗后PpIX自体荧光或诱导的PpIX荧光的变化。
将使用人乳头瘤病毒16型蛋白E6和E7永生化的高致瘤性TC-1细胞皮下移植到裸鼠大腿。在给予5-ALA的情况下，使用自体荧光成像和诱导荧光成像观察疑似肿瘤组织。当5-ALA诱导的PpIX在肿瘤组织中充分积累后，使用635nm激光进行PDT。我们观察了PDT期间荧光强度的变化。在PDT后3周，我们使用白光成像和荧光成像监测肿瘤缓解情况。
通过血红素合成诱导的PpIX自体荧光可使移植细胞可视化。给予5-ALA后，PpIX可通过PDT靶向，这降低了PpIX自体荧光。光漂白有助于监测PDT剂量测定并确定对治疗的光动力反应。
PpIX自体荧光可清晰区分肿瘤与相邻正常组织。PpIX自体荧光成像和5-ALA诱导的荧光成像结果相同。PpIX自体荧光成像是一种简单且经济高效的宫颈癌筛查方法，可在PDT期间或之后进行，以确保有效治疗或缓解，因为可以实时观察荧光强度的变化而无致盲效应。
