Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.
VA San Diego Healthcare System, San Diego, CA, U.S.A.
In Vivo. 2021 Jul-Aug;35(4):1959-1963. doi: 10.21873/invivo.12463.
BACKGROUND/AIM: During surgical resection of gastroesophageal-junction (GEJ) adenocarcinoma, the margin status is often difficult to visualize resulting in high recurrence rates. The aim of the present study was to develop a labelling technique that would allow improved visualization of GEJ tumor margins for surgeons to reduce recurrence rates in a patient-like model.
A patient GEJ tumor was obtained from an endoscopic biopsy and implanted subcutaneously in a nude mouse. A patient-derived orthotopic xenograft (PDOX) model was established by implanting tumor fragments grown from a subcutaneous model to the cardia of the stomach of nude mice. CC1/3/5-SAB, an antibody to carcinoembryonic-antigen-related cell-adhesion molecules, was conjugated with infrared dye IRDye800 to create SAB-IR800. Forty-eight hours after i.v. injection of SAB-IR800, GEJ-PDOX mice were imaged.
Fluorescence imaging with SAB-IR800 brightly visualized the GEJ adenocarcinoma demonstrating specific targeting. In the PDOX model, injection of SAB-IR800 (50 μg) resulted in a tumor to background ratio of 1.78 at 48 hours and 1.86 at 72 hours.
PDOX models of GEJ tumors can be established from patients by endoscopic biopsy without undergoing surgical resection. GEJ PDOX models should be useful for developing novel diagnostics and therapeutics for this recalcitrant disease.
背景/目的：在胃食管交界处（GEJ）腺癌的手术切除过程中，由于边缘状态难以可视化，导致复发率较高。本研究旨在开发一种标记技术，使外科医生能够更好地观察 GEJ 肿瘤的边缘，从而降低患者模型中的复发率。
从内镜活检中获得患者的 GEJ 肿瘤，并将其皮下植入裸鼠体内。通过将从皮下模型中生长的肿瘤碎片植入裸鼠胃的贲门来建立患者来源的原位异种移植（PDOX）模型。将针对癌胚抗原相关细胞黏附分子的抗体 CC1/3/5-SAB 与近红外染料 IRDye800 缀合，以创建 SAB-IR800。在静脉注射 SAB-IR800 后 48 小时，对 GEJ-PDOX 小鼠进行成像。
SAB-IR800 的荧光成像可清晰地显示出具有特异性靶向性的 GEJ 腺癌。在 PDOX 模型中，注射 SAB-IR800（50μg）后，48 小时和 72 小时时肿瘤与背景的比值分别为 1.78 和 1.86。
可以通过内镜活检从患者中建立 GEJ 肿瘤的 PDOX 模型，而无需进行手术切除。GEJ PDOX 模型对于开发这种难治性疾病的新型诊断和治疗方法应该是有用的。
