124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results.
124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results.
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DOI：
10.1186/1477-7819-8-65
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发表时间：
2010-08-06
影响因子：
3.2
通讯作者：
Sun D
中科院分区：
文献类型：
--
作者：
Zou P;Povoski SP;Hall NC;Carlton MM;Hinkle GH;Xu RX;Mojzisik CM;Johnson MA;Knopp MV;Martin EW Jr;Sun D
18F-脱氧葡萄糖正电子发射断层扫描(18F-FDG-PET)广泛应用于肿瘤影像诊断。然而，18F-FDG在基于PET的成像中的使用受到其特异性和敏感性的限制。相反，抗TAG(肿瘤相关糖蛋白)-72的单抗与包括结直肠癌在内的各种腺癌的结合具有高度的特异性。这项初步研究的目的是评价一种免费的决定区域(CDR)嫁接的CH2结构域缺失的人源化抗TAG-72单抗(HuCC49deltaCH2)，并用碘-124(124I)标记，作为一种抗原导向和肿瘤特异性的PET成像靶向试剂。用124I标记HuCC49deltaCH2。将表达TAG-72抗原的LS174T结肠腺癌细胞接种于裸鼠皮下作为移植瘤模型。血管内(静脉注射)和腹膜腔(I.P.)然后在注射后约1小时至24小时的不同时间点，使用microPET成像技术在该异种移植小鼠模型中评估124I-HuCC49deltaCH2的给药情况。这与静脉注射进行了比较。注射后50分钟，在相同的异种移植小鼠模型上注射18F-FDG，使用microPET成像。大约在静脉注射后1小时。注射，124I-HuCC49deltaCH2在体循环中分布，大约在ip后1小时。注射，124I-HuCC49deltaCH2分布于腹膜腔内。静脉注射后18小时至24小时的时间点。和IP。注射124I-HuCC49deltaCH2后，与1小时成像相比，124I-HuCC49deltaCH2对LS174T肿瘤种植体的特异性定位水平显著提高(p=0.001)。相比之下，静脉注射后大约50分钟。注射后，18F-FDG未能显示出对LS174T肿瘤植入物的任何特异性定位水平的增加，但显示出心脏、眼眶骨性哈德氏腺、后颈、肾脏和膀胱的棕色脂肪更倾向于非特异性摄取。在microPET成像中，124I-HuCC49deltaCH2在延迟成像中显示对移植瘤小鼠模型中LS174T结肠腺癌细胞的特异性定位增加，而18F-FDG未能证明这一点。124I-HuCC49deltaCH2是一种抗原导向的癌症特异性抗TAG-72单抗结合物，可用于术前、术中和术后的基于PET的成像策略的人类临床试验，包括基于融合模式的PET成像平台。
18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is widely used in diagnostic cancer imaging. However, the use of 18F-FDG in PET-based imaging is limited by its specificity and sensitivity. In contrast, anti-TAG (tumor associated glycoprotein)-72 monoclonal antibodies are highly specific for binding to a variety of adenocarcinomas, including colorectal cancer. The aim of this preliminary study was to evaluate a complimentary determining region (CDR)-grafted humanized CH2-domain-deleted anti-TAG-72 monoclonal antibody (HuCC49deltaCH2), radiolabeled with iodine-124 (124I), as an antigen-directed and cancer-specific targeting agent for PET-based imaging. HuCC49deltaCH2 was radiolabeled with 124I. Subcutaneous tumor implants of LS174T colon adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu nude mice as the xenograft model. Intravascular (i.v.) and intraperitoneal (i.p.) administration of 124I-HuCC49deltaCH2 was then evaluated in this xenograft mouse model at various time points from approximately 1 hour to 24 hours after injection using microPET imaging. This was compared to i.v. injection of 18F-FDG in the same xenograft mouse model using microPET imaging at 50 minutes after injection. At approximately 1 hour after i.v. injection, 124I-HuCC49deltaCH2 was distributed within the systemic circulation, while at approximately 1 hour after i.p. injection, 124I-HuCC49deltaCH2 was distributed within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v. and i.p. injection, 124I-HuCC49deltaCH2 demonstrated a significantly increased level of specific localization to LS174T tumor implants (p = 0.001) when compared to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection, 18F-FDG failed to demonstrate any increased level of specific localization to a LS174T tumor implant, but showed the propensity toward more nonspecific uptake within the heart, Harderian glands of the bony orbits of the eyes, brown fat of the posterior neck, kidneys, and bladder. On microPET imaging, 124I-HuCC49deltaCH2 demonstrates an increased level of specific localization to tumor implants of LS174T colon adenocarcinoma cells in the xenograft mouse model on delayed imaging, while 18F-FDG failed to demonstrate this. The antigen-directed and cancer-specific 124I-radiolabled anti-TAG-72 monoclonal antibody conjugate, 124I-HuCC49deltaCH2, holds future potential for use in human clinical trials for preoperative, intraoperative, and postoperative PET-based imaging strategies, including fused-modality PET-based imaging platforms.
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影响因子：
3.7
作者：
Bakalakos, EA;Young, DC;Martin, EW
通讯作者：
Martin, EW
DOI：
10.1053/ejso.2000.1108
发表时间：
2001-04-01
期刊：
EUROPEAN JOURNAL OF SURGICAL ONCOLOGY
影响因子：
--
作者：
Haddad, R;Avital, S;Schneebaum, S
通讯作者：
Schneebaum, S
影响因子：
4.9
作者：
Cherry SR
通讯作者：
Cherry SR
影响因子：
3.3
作者：
Endo, Keigo;Oriuchi, Noboru;Koyama, Keiko
通讯作者：
Koyama, Keiko
影响因子：
3.7
作者：
Bertsch, DJ;Burak, WE;Martin, WE
通讯作者：
Martin, WE