Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Chemistry, Purdue University, West Lafayette, IN, USA.
Mol Imaging Biol. 2021 Feb;23(1):11-17. doi: 10.1007/s11307-020-01549-x. Epub 2020 Oct 8.
Current methods of assessing disease burden in gastric adenocarcinoma are imperfect. Improved visualization during surgery with intraoperative molecular imaging (IMI) could improve gastric adenocarcinoma staging and guide surgical decision-making. The goal of this study was to evaluate if IMI with a folate receptor-targeted near-infrared fluorescent agent, OTL38, could identify gastric adenocarcinomas during surgery.
Five patients were enrolled in an IMI clinical trial. Patients received a folate receptor-targeted near-infrared dye (OTL38) 1.5-6 h prior to surgery. During staging laparoscopy and gastric resection, IMI was utilized to identify the primary tumor and any fluorescent lymph nodes. Resected tumors were analyzed for folate receptor alpha (FRα) and CD68 expression using immunohistochemistry. Microscopic OTL38 accumulation was examined with immunofluorescence.
Four out of five patients underwent total or subtotal gastrectomy; one had a staging laparoscopy only. All four patients who underwent gastric resection had invasive gastric adenocarcinoma; three had fluorescent tumors, mean tumor to background ratio (TBR) 4.1 ± 2.9. The one patient with a non-fluorescent tumor had a T1a tumor with two 0.4 cm tumor foci within a larger polyp. In each case with a fluorescent tumor, the fluorescence was evident from the exterior of the stomach. Two of the fluorescent tumors had modest FRα expression and no CD68 expression. One fluorescent tumor had high CD68 expression and no FRα expression.
Intraoperative molecular imaging of gastric adenocarcinoma with OTL38 is feasible. Further studies should evaluate the clinical utility of this technique.
目前评估胃腺癌疾病负担的方法并不完善。术中分子成像(IMI)可改善手术期间的可视化效果,从而提高胃腺癌分期并指导手术决策。本研究旨在评估叶酸受体靶向近红外荧光剂 OTL38 能否在手术期间识别胃腺癌。
5 名患者入组了一项 IMI 临床试验。患者在手术前 1.5-6 小时接受叶酸受体靶向近红外染料(OTL38)。在分期腹腔镜检查和胃切除术中,使用 IMI 识别原发性肿瘤和任何荧光性淋巴结。使用免疫组织化学分析切除的肿瘤中叶酸受体α(FRα)和 CD68 的表达。用免疫荧光法检查 OTL38 的微观积累。
5 名患者中有 4 名接受了全胃或胃大部切除术;1 名仅接受了分期腹腔镜检查。所有 4 名接受胃切除术的患者均患有浸润性胃腺癌;3 例肿瘤荧光,平均肿瘤与背景比值(TBR)为 4.1±2.9。唯一一名非荧光肿瘤患者的 T1a 肿瘤内有两个 0.4cm 的肿瘤灶,位于较大的息肉内。每个荧光肿瘤均从胃外部即可明显看到荧光。2 个荧光肿瘤 FRα 表达适度,无 CD68 表达。一个荧光肿瘤高表达 CD68,无 FRα 表达。
使用 OTL38 对胃腺癌进行术中分子成像可行。进一步的研究应评估该技术的临床实用性。