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肿瘤特异性荧光抗体成像可在胰腺癌原位模型中实现准确的分期腹腔镜检查。

Tumor-specific fluorescence antibody imaging enables accurate staging laparoscopy in an orthotopic model of pancreatic cancer.

作者信息

Tran Cao Hop S, Kaushal Sharmeela, Metildi Cristina A, Menen Rhiana S, Lee Claudia, Snyder Cynthia S, Messer Karen, Pu Minya, Luiken George A, Talamini Mark A, Hoffman Robert M, Bouvet Michael

机构信息

University of California San Diego, San Diego, CA, USA.

出版信息

Hepatogastroenterology. 2012 Sep;59(118):1994-9. doi: 10.5754/hge11836.

DOI:10.5754/hge11836
PMID:22369743
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4096574/
Abstract

BACKGROUND/AIMS: Laparoscopy is important in staging pancreatic cancer, but false negatives remain problematic. Making tumors fluorescent has the potential to improve the accuracy of staging laparoscopy.

METHODOLOGY

Orthotopic and carcinomatosis models of pancreatic cancer were established with BxPC-3 human pancreatic cancer cells in nude mice. Alexa488-antiCEA conjugates were injected via tail vein 24 hours prior to laparoscopy. Mice were examined under bright field laparoscopic (BL) and fluorescence laparoscopic (FL) modes. Outcomes measured included time to identification of primary tumor for the orthotopic model and number of metastases identified within 2 minutes for the carcinomatosis model.

RESULTS

FL enabled more rapid and accurate identification and localization of primary tumors and metastases than BL. Using BL took statistically significantly longer time than FL (p<0.0001, fold change and 95% CI for BL vs. FL: 8.12 (4.54,14.52)). More metastatic lesions were detected and localized under FL compared to BL and with greater accuracy, with sensitivities of 96% vs. 40%, respectively, when compared to control. FL was sensitive enough to detect metastatic lesions <1mm.

CONCLUSIONS

The use of fluorescence laparoscopy with tumors labeled with fluorophore-conjugated anti-CEA antibody permits rapid detection and accurate localization of primary and metastatic pancreatic cancer in an orthotopic model. The results of the present report demonstrate the future clinical potential of fluorescence laparoscopy.

摘要

背景/目的:腹腔镜检查在胰腺癌分期中很重要,但假阴性结果仍然存在问题。使肿瘤产生荧光有可能提高腹腔镜分期的准确性。

方法

用BxPC-3人胰腺癌细胞在裸鼠中建立胰腺癌原位模型和癌转移模型。在腹腔镜检查前24小时经尾静脉注射Alexa488-抗癌胚抗原(CEA)偶联物。在明场腹腔镜(BL)和荧光腹腔镜(FL)模式下检查小鼠。测量的结果包括原位模型中识别原发性肿瘤的时间以及癌转移模型中2分钟内识别出的转移灶数量。

结果

与BL相比,FL能够更快速、准确地识别和定位原发性肿瘤和转移灶。使用BL识别肿瘤所需的时间在统计学上显著长于FL(p<0.0001,BL与FL的倍数变化和95%置信区间:8.12(4.54,14.52))。与BL相比,FL能检测到更多的转移病灶,定位更准确,与对照组相比,灵敏度分别为96%和40%。FL足够灵敏,能够检测到小于1mm的转移病灶。

结论

使用荧光腹腔镜检查并结合荧光团偶联的抗CEA抗体标记肿瘤,能够在原位模型中快速检测并准确定位原发性和转移性胰腺癌。本报告的结果证明了荧光腹腔镜检查在未来临床应用中的潜力。

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