Ex-vivo Imaging of Upper Tract Urothelial Carcinoma Using Novel pH Low Insertion Peptide (Variant 3), a Molecular Imaging Probe.

Ex-vivo Imaging of Upper Tract Urothelial Carcinoma Using Novel pH Low Insertion Peptide (Variant 3), a Molecular Imaging Probe.
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DOI:
10.1016/j.urology.2019.01.008
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发表时间:
2020-05
期刊:
影响因子:
2.1
通讯作者:
Golijanin D
Golijanin D
中科院分区:
医学4区
文献类型:
--
作者:
Brito J;Golijanin B;Kott O;Moshnikova A;Mueller-Leonhard C;Gershman B;Andreev OA;Reshetnyak YK;Amin A;Golijanin D

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提高上尿路上皮癌的显示率。先前使用新的pH低插入肽(pHLIP)变体3(Var 3)缀合吲哚菁绿色(ICG)的研究已经证明了膀胱尿路上皮癌成像的高灵敏度和特异性。在这里,我们描述了一种新的方法,上尿路上皮癌的成像ICG-Var 3 pHLIP。用ICG-Var 3 pHLIP冲洗12个离体上尿路标本15分钟,然后使用白色光腹腔镜照相机进行检查,随后使用斯特赖克1588 AIM成像系统进行近红外荧光(NIRF)成像。进行标准组织病理学评价,并将结果与白色光和ICG-Var 3 NIRF成像相关联。1例因肾细胞癌行根治性肾切除术的患者用作阴性对照。10例患者的组织病理学评价确定了19个病变,其中82%为高级别尿路上皮癌,18%为低级别尿路上皮癌。19个(100%)恶性病变被确定使用NIRF成像,而15个(78.9%)病变被确定使用传统的白色光检查。ICG-Var 3 pHLIP NIRF成像的灵敏度为100%,而白色光检查的灵敏度为78.9%。这两种模式都是100%特定的。良性集合系统和输尿管没有显示pHLIP构建体的摄取。在该可行性研究中,ICG-Var 3 pHLIP成像剂表现出上级传统白色检查的诊断性能。虽然验证和体内翻译需要额外的研究,但基于pHLIP的成像是一种有前途的工具,可以改善上尿路上皮癌的评估和管理。泌尿学139:134-140,2020。
To improve visualization of upper tract urothelial carcinomas. Previous studies using the novel pH low insertion peptide (pHLIP) variant 3 (Var3) conjugated to indocyanine green (ICG) have demonstrated high sensitivity and specificity for imaging of bladder urothelial carcinoma. Here, we describe a novel approach for the imaging of upper tract urothelial carcinomas using ICG-Var3 pHLIP. Twelve ex-vivo upper urinary tract specimens were irrigated with ICG-Var 3 pHLIP for 15 minutes and then examined using a white light laparoscopic camera followed by near infrared fluorescent (NIRF) imaging using a Stryker 1588 AIM imaging system. Standard histopathologic evaluation was performed and findings were correlated with white light and ICG-Var3 NIRF imaging. One patient who underwent radical nephrectomy for renal cell carcinoma was used as a negative control. Nineteen lesions were identified on histopathologic evaluation in 10 patients, including 82% high-grade urothelial carcinoma and 18% low-grade urothelial carcinoma. Nineteen (100%) malignant lesions were identified using NIRF imaging, while 15 (78.9%) lesions were identified using conventional white light examination. The sensitivity of ICG-Var3 pHLIP NIRF imaging was 100% compared to 78.9% white light examination. Both modalities are 100% specific. Benign collecting systems and ureters did not show uptake of the pHLIP construct. In this feasibility study, the ICG-Var3 pHLIP imaging agent demonstrated superior diagnostic performance compared to conventional white light examination. While additional studies are required for validation and in-vivo translation, pHLIP-based imaging represents a promising tool to improve the evaluation and management of upper tract urothelial carcinoma. UROLOGY 139: 134–140, 2020.
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