Tumor-Specific Labeling of Pancreatic Cancer Using a Humanized Anti-CEA Antibody Conjugated to a Near-Infrared Fluorophore.
Tumor-Specific Labeling of Pancreatic Cancer Using a Humanized Anti-CEA Antibody Conjugated to a Near-Infrared Fluorophore.
复制标题
DOI：
10.1245/s10434-018-6344-6
复制
发表时间：
2018-04
影响因子：
3.7
通讯作者：
Bouvet M
中科院分区：
文献类型：
--
作者：
Lwin TM;Murakami T;Miyake K;Yazaki PJ;Shivley JE;Hoffman RM;Bouvet M
一种人源化荧光团偶联抗体的开发，可提高荧光引导肿瘤手术的对比度。将BxPC-3-GFP胰腺癌细胞接种于裸鼠腹侧。将皮下肿瘤的碎片移植到受体小鼠的胰腺尾部，以建立胰腺癌的原位异种移植模型。肿瘤形成4周后，将人源化抗CEA抗体与800 nm近红外荧光染料(hM5A-IR800)偶联，静脉注射。分别于注射后6、12、24、48、72小时对小鼠进行成像。荧光成像显示hM5A-IR800特异性地定位于BxPC-3人胰腺癌细胞。该荧光探针在体外定位于细胞表面，并在体内原位异种胰腺移植模型中与GFP标记的肿瘤特异性地共定位。特定时间点的序列成像显示原位胰腺肿瘤的信号强度在48h达到峰值，该时间点对应的肿瘤/背景比在48h达到最大值21.23。HM5A-IR800成功地对原位胰腺肿瘤进行了特异性标记。较长的波长允许更深的组织渗透，特别是在被正常胰腺实质覆盖的肿瘤区域。该探针曾预期抗体-荧光团偶联的动力学，峰值信号强度在48小时达到。肿瘤信号清晰，肿瘤背景比(TBR)在各时间点均大于5，48h时为高对比度(TBR为16.6)。HM5A-IR800显示良好的肿瘤定位和非常明亮的信号。它是未来临床荧光引导手术应用的一种很有前途的试剂。
Development of a humanized fluorophore-conjugated antibody that can improve contrast for fluorescence guided oncologic surgeries. BxPC-3-GFP pancreatic cancer cells were injected into flanks of nude mice. Fragments of subcutaneous tumors were grafted onto the pancreatic tail of recipient mice to create orthotopic xenograft models of pancreatic cancer. After tumors developed for 4 weeks, a humanized anti-CEA antibody conjugated to an 800 nm NIR fluorescent dye (hM5A-IR800), was injected intravenously. Mice were imaged at 6, 12, 24, 48, and 72 hours after injection. Fluorescence imaging showed that hM5A-IR800 specifically localized to BxPC-3 human pancreatic cancer cells. The fluorescent probe localized to cell surfaces in-vitro and specifically co-localized with GFP labeled tumors in an orthotopic pancreatic xenograft model in-vivo. Serial imaging at specific time points showed peak signal intensity of the orthotopic pancreatic tumor at 48 hours and this time point corresponded with a maximal tumor to background ratio of 21.23 at 48 hours. hM5A-IR800 was successfully able to specifically label orthotopic pancreatic tumors in-situ. The longer wavelength allowed deeper tissue penetration, particularly in tumor areas covered by normal pancreatic parenchyma. The probe had expected kinetics for an antibody-fluorophore conjugate with the peak signal intensity reached at 48 hours. There was a clear tumor signal with a tumor-to-background ratio (TBR) greater than 5 at all time points, with high contrast (TBR of 16.6) at 48 hours. hM5A-IR800 demonstrated excellent tumor localization and a very bright signal. It is a promising agent for future clinical fluorescence-guided surgery applications.
登录
查看更多内容
影响因子：
2.5
作者：
YAMAGUCHI, K;ENJOJI, M;TSUNEYOSHI, M
通讯作者：
TSUNEYOSHI, M
影响因子：
6.4
作者：
Matsuo, Yoichi;Raimondo, Massimo;Guha, Sushovan
通讯作者：
Guha, Sushovan
影响因子：
3.2
作者：
Kaushal, Sharmeela;McElroy, Michele K.;Luiken, George A.;Talamini, Mark A.;Moossa, A. R.;Hoffman, Robert M.;Bouvet, Michael
通讯作者：
Bouvet, Michael
影响因子：
3.7
作者：
Metildi, Cristina A.;Tang, Chih-Min;Sicklick, Jason K.
通讯作者：
Sicklick, Jason K.
影响因子：
4.5
作者：
Abuqayyas, Lubna;Balthasar, Joseph P.
通讯作者：
Balthasar, Joseph P.