Prince Andrew C, Jani Aditi, Korb Melissa, Tipirneni Kiranya E, Kasten Benjamin B, Rosenthal Eben L, Warram Jason M
School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
J Surg Oncol. 2017 Dec;116(7):898-906. doi: 10.1002/jso.24733. Epub 2017 Jun 19.
Optical imaging to guide cancer resections is rapidly transitioning into the operating room. However, the sensitivity of this technique to detect subclinical disease is yet characterized. The purpose of this study was to determine the minimum range of cancer cells that can be detected by antibody-based fluorescence imaging.
2LMP (breast), COLO-205 (colon), MiaPaca-2 (pancreas), and SCC-1 (head and neck) cells incubated in vitro with cetuximab-IRDye800CW (dose range 8.6-86 nM) were implanted subcutaneously in mice (n = 3 mice, 5 tumors/mouse). Following incubation with 8.6 × 10 µM of cetuximab-IRDye800CW in vitro, serial dilutions of each cell type (1 × 10 -1 × 10 ) were implanted subcutaneously (n = 3, 5 tumors/mouse). Tumors were imaged with Pearl Impulse and Xenogen IVIS 100 imaging systems. Scatchard analysis was performed to determine receptor density and kinetics for each cell line.
Under conditions of minimal cetuximab-IRDye800CW exposure to low cellular quantity, closed-field fluorescence imaging theoretically detected a minimum of 4.2 × 10 -9.5 × 10 2LMP cells, 1.9 × 10 -4.5 × 10 MiaPaca-2 cells, and 2.4 × 10 -6.7 × 10 SCC-1 cells; COLO-205 cells could not be identified. Higher EGFR-mediated uptake of cetuximab correlated with sensitivity of detection.
This study supports the clinical utility of cetuximab-IRDye800CW to sensitively localize subclinical disease in the surgical setting.
用于指导癌症切除术的光学成像正迅速进入手术室。然而，该技术检测亚临床疾病的敏感性尚未得到明确。本研究的目的是确定基于抗体的荧光成像能够检测到的癌细胞的最小数量范围。
将在体外与西妥昔单抗-IRDye800CW（剂量范围8.6 - 86 nM）孵育的2LMP（乳腺）、COLO-205（结肠）、MiaPaca-2（胰腺）和SCC-1（头颈部）细胞皮下植入小鼠体内（n = 3只小鼠，每只小鼠5个肿瘤）。在体外与8.6×10 µM的西妥昔单抗-IRDye800CW孵育后，将每种细胞类型的系列稀释液（1×10 - 1×10 ）皮下植入（n = 3，每只小鼠5个肿瘤）。用Pearl Impulse和Xenogen IVIS 100成像系统对肿瘤进行成像。进行Scatchard分析以确定每种细胞系的受体密度和动力学。
在西妥昔单抗-IRDye800CW暴露量最小且细胞数量较少的条件下，封闭场荧光成像理论上检测到的最小细胞数量为：4.2×10 - 9.5×10 个2LMP细胞、1.9×10 - 4.5×10 个MiaPaca-2细胞和2.4×10 - 6.7×10 个SCC-1细胞；无法识别COLO-205细胞。西妥昔单抗更高的表皮生长因子受体介导摄取与检测敏感性相关。
本研究支持西妥昔单抗-IRDye800CW在手术环境中灵敏定位亚临床疾病的临床应用价值。
