de Visscher Sebastiaan A H J, Witjes Max J H, van der Vegt Bert, de Bruijn Henriëtte S, van der Ploeg-van den Heuvel Angélique, Amelink Arjen, Sterenborg Henricus J C M, Roodenburg Jan L N, Robinson Dominic J
Department of Oral and Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, The Netherlands.
Lasers Surg Med. 2013 Dec;45(10):668-78. doi: 10.1002/lsm.22197. Epub 2013 Oct 30.
Foslip and Fospeg are liposomal formulations of the photosensitizer mTHPC (Foscan), which is used for photodynamic therapy (PDT) of malignancies. Literature suggests that liposomal mTHPC formulations have better properties and increased tumor uptake compared to Foscan. To investigate this, we used the 4NQO-induced carcinogen model to compare the localization of the different mTHPC formulations within normal, precancerous, and cancerous tissue. In contrast to xenograft models, the 4NQO model closely mimics the carcinogenesis of human oral dysplasia.
Fifty-four rats drank water with the carcinogen 4NQO. When oral examination revealed tumor, the rats received 0.15 mg/kg mTHPC (Foscan, Foslip, or Fospeg). At 2, 4, 8, 24, 48, or 96 hours after injection the rats were sacrificed. Oral tissue was sectioned for HE slides and for fluorescence confocal microscopy. The HE slides were scored on the severity of dysplasia by the epithelial atypia index (EAI). The calibrated fluorescence intensity per formulation or time point was correlated to EAI.
Fospeg showed higher mTHPC fluorescence in normal and tumor tissue compared to both Foscan and Foslip. Significant differences in fluorescence between tumor and normal tissue were found for all formulations. However, at 4, 8, and 24 hours only Fospeg showed a significant difference. The Pearson's correlation between EAI and mTHPC fluorescence proved weak for all formulations.
In our induced carcinogenesis model, Fospeg exhibited a tendency for higher fluorescence in normal and tumor tissue compared to Foslip and Foscan. In contrast to Foscan and Foslip, Fospeg showed significantly higher fluorescence in tumor versus normal tissue at earlier time points, suggesting a possible clinical benefit compared to Foscan. Low correlation between grade of dysplasia and mTHPC fluorescence was found.
Foslip和Fospeg是光敏剂mTHPC（Foscan）的脂质体制剂，用于恶性肿瘤的光动力疗法（PDT）。文献表明，与Foscan相比，脂质体mTHPC制剂具有更好的性能且肿瘤摄取增加。为了对此进行研究，我们使用4NQO诱导的致癌物模型来比较不同mTHPC制剂在正常、癌前和癌组织中的定位。与异种移植模型不同，4NQO模型紧密模拟人类口腔发育异常的致癌过程。
54只大鼠饮用含致癌物4NQO的水。当口腔检查发现肿瘤时，大鼠接受0.15mg/kg的mTHPC（Foscan、Foslip或Fospeg）。注射后2、4、8、24、48或96小时处死大鼠。将口腔组织切片用于制作HE玻片和进行荧光共聚焦显微镜检查。通过上皮异型指数（EAI）对HE玻片上发育异常的严重程度进行评分。将每种制剂或时间点的校准荧光强度与EAI相关联。
与Foscan和Foslip相比，Fospeg在正常组织和肿瘤组织中显示出更高的mTHPC荧光。所有制剂在肿瘤组织和正常组织之间的荧光均存在显著差异。然而，仅在4、8和24小时时Fospeg显示出显著差异。所有制剂的EAI与mTHPC荧光之间的皮尔逊相关性均较弱。
在我们的诱导致癌模型中，与Foslip和Foscan相比，Fospeg在正常组织和肿瘤组织中表现出更高荧光的趋势。与Foscan和Foslip不同，Fospeg在较早时间点的肿瘤组织与正常组织中显示出显著更高的荧光，提示与Foscan相比可能具有临床益处。发现发育异常程度与mTHPC荧光之间的相关性较低。
