Tumor-Specific Zr-89 Immuno-PET Imaging in a Human Bladder Cancer Model.
Tumor-Specific Zr-89 Immuno-PET Imaging in a Human Bladder Cancer Model.
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DOI：
10.1007/s11307-018-1177-z
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发表时间：
2018-10
影响因子：
3.1
通讯作者：
Houghton JL
中科院分区：
文献类型：
--
作者：
Escorcia FE;Steckler JM;Abdel-Atti D;Price EW;Carlin SD;Scholz WW;Lewis JS;Houghton JL
肿瘤特异性分子成像是评估疾病负担和治疗反应的重要工具。 CA19.9 是多种恶性肿瘤（包括尿路上皮癌）中重要的肿瘤特异性标志物。 [89Zr]DFO-HuMab-5B1 (MVT-2163) 是一种基于 CA19.9 特异性抗体的构建体，已在肺、结直肠和胰腺恶性肿瘤的临床前动物模型中进行正电子发射断层扫描 (PET) 成像验证，目前正在进行胰腺癌的 I 期试验 (NCT02687230)。在这里，我们检查 [89Zr]DFO-HuMab-5B1 是否可用于定义尿路上皮恶性肿瘤。 CA19.9的表面表达在人膀胱癌系HT 1197中得到证实。将放射免疫缀合物[89Zr]DFO-HuMab-5B1注射到携带HT 1197异种移植物的小鼠中，然后进行PET成像、离体实验（包括生物分布、组织学和放射自显影）以及对血液样本的脱落抗原水平进行分析。当使用 PET 成像时，[89Zr]DFO-HuMab-5B1 特异性地积聚在 HT 1197 移植的肿瘤中。器官的离体生物分布和移植肿瘤的放射自显影证实了我们的构建体的特异性肿瘤结合。未发现靶抗原CA19.9在体外或体内脱落。 [89Zr]DFO-HuMab-5B1 可用于通过 PET 成像描绘尿路上皮癌，并可在全身治疗之前、期间和之后提供肿瘤特异性信息。
Tumor-specific molecular imaging is an important tool for assessing disease burden and treatment response. CA19.9 is an important tumor-specific marker in several malignancies, including urothelial carcinoma. [89Zr]DFO-HuMab-5B1 (MVT-2163) is a CA19.9-specific antibody-based construct that has been validated in preclinical animal models of lung, colorectal, and pancreatic malignancies for positron emission tomography (PET) imaging and is currently in a phase I trial for pancreatic cancer (NCT02687230). Here, we examine whether [89Zr]DFO-HuMab-5B1 may be useful in defining urothelial malignancies. Surface expression of CA19.9 was confirmed in the human bladder cancer line HT 1197. The radioimmunoconjugate [89Zr]DFO-HuMab-5B1 was injected into mice bearing HT 1197 xenografts, and followed by PET imaging, ex vivo experiments including biodistribution, histology and autoradiography, and analysis of blood samples for shed antigen levels were performed. [89Zr]DFO-HuMab-5B1 specifically accumulates in HT 1197 engrafted tumors when imaged with PET. Ex vivo biodistribution of organs and autoradiography of engrafted tumors confirm our construct’s specific tumor binding. The target antigen CA19.9 was not found to be shed in vitro or in vivo. [89Zr]DFO-HuMab-5B1 can be used to delineate urothelial carcinomas by PET imaging and may provide tumor-specific information prior to, during, and after systemic therapies.
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影响因子：
4.7
作者：
Meyer JP;Houghton JL;Kozlowski P;Abdel-Atti D;Reiner T;Pillarsetty NV;Scholz WW;Zeglis BM;Lewis JS
通讯作者：
Lewis JS
DOI：
10.2967/jnumed.115.163824
发表时间：
2016-03
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Houghton JL;Zeglis BM;Abdel-Atti D;Sawada R;Scholz WW;Lewis JS
通讯作者：
Lewis JS
影响因子：
4.7
作者：
Deri MA;Ponnala S;Kozlowski P;Burton-Pye BP;Cicek HT;Hu C;Lewis JS;Francesconi LC
通讯作者：
Francesconi LC
影响因子：
78.5
作者：
Kufe, Donald W.
通讯作者：
Kufe, Donald W.
DOI：
10.1016/s0140-6736(16)00561-4
发表时间：
2016-05-07
期刊：
Lancet (London, England)
影响因子：
--
作者：
Rosenberg JE;Hoffman-Censits J;Powles T;van der Heijden MS;Balar AV;Necchi A;Dawson N;O'Donnell PH;Balmanoukian A;Loriot Y;Srinivas S;Retz MM;Grivas P;Joseph RW;Galsky MD;Fleming MT;Petrylak DP;Perez-Gracia JL;Burris HA;Castellano D;Canil C;Bellmunt J;Bajorin D;Nickles D;Bourgon R;Frampton GM;Cui N;Mariathasan S;Abidoye O;Fine GD;Dreicer R
通讯作者：
Dreicer R