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采用双标记抗碳酸酐酶 IX 抗体 G250 对透明细胞肾细胞癌进行放射性核素和荧光成像。

Radionuclide and Fluorescence Imaging of Clear Cell Renal Cell Carcinoma Using Dual Labeled Anti-Carbonic Anhydrase IX Antibody G250.

机构信息

Radboud University Medical Center, Nijmegen, The Netherlands.

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.

出版信息

J Urol. 2015 Aug;194(2):532-8. doi: 10.1016/j.juro.2015.02.041. Epub 2015 Feb 14.

Abstract

PURPOSE

Tumor targeted optical imaging using antibodies labeled with near infrared fluorophores is a sensitive imaging modality that might be used during surgery to assure complete removal of malignant tissue. We evaluated the feasibility of dual modality imaging and image guided surgery with the dual labeled anti-carbonic anhydrase IX antibody preparation (111)In-DTPA-G250-IRDye800CW in mice with intraperitoneal clear cell renal cell carcinoma.

MATERIALS AND METHODS

BALB/c nu/nu mice with intraperitoneal SK-RC-52 lesions received 10 μg DTPA-G250-IRDye800CW labeled with 15 MBq (111)In or 10 μg of the dual labeled irrelevant control antibody NUH-82 (20 mice each). To evaluate when tumors could be detected, 4 mice per group were imaged weekly during 5 weeks with single photon emission computerized tomography/computerized tomography and the fluorescence imaging followed by ex vivo biodistribution studies.

RESULTS

As early as 1 week after tumor cell inoculation single photon emission computerized tomography and fluorescence images showed clear delineation of intraperitoneal clear cell renal cell carcinoma with good concordance between single photon emission computerized tomography/computerized tomography and fluorescence images. The high and specific accumulation of the dual labeled antibody conjugate in tumors was confirmed in the biodistribution studies. Maximum tumor uptake was observed 1 week after inoculation (mean ± SD 58.5% ± 18.7% vs 5.6% ± 2.3% injected dose per gm for DTPA-G250-IRDye800CW vs NUH-82, respectively). High tumor uptake was also observed at other time points.

CONCLUSIONS

This study demonstrates the feasibility of dual modality imaging with dual labeled antibody (111)In-DTPA-G250-IRDye800CW in a clear cell renal cell carcinoma model. Results indicate that preoperative and intraoperative detection of carbonic anhydrase IX expressing tumors, positive resection margins and metastasis might be feasible with this approach.

摘要

目的

使用近红外荧光团标记的抗体进行肿瘤靶向光学成像是一种敏感的成像方式,可用于手术期间以确保恶性组织的完全切除。我们评估了双模态成像和图像引导手术的可行性,方法是使用双标记的抗碳酸酐酶 IX 抗体制剂(111)In-DTPA-G250-IRDye800CW 在患有腹腔透明细胞肾细胞癌的小鼠中进行。

材料和方法

接受腹腔 SK-RC-52 病变的 BALB/c nu/nu 小鼠接受了 10 μg DTPA-G250-IRDye800CW 标记有 15 MBq(111)In 或 10 μg 双标记无关对照抗体 NUH-82(每组 20 只)。为了评估何时可以检测到肿瘤,每组 4 只小鼠每周进行单光子发射计算机断层扫描/计算机断层扫描和荧光成像,然后进行离体生物分布研究。

结果

早在肿瘤细胞接种后 1 周,单光子发射计算机断层扫描和荧光图像就清晰地描绘了腹腔透明细胞肾细胞癌,单光子发射计算机断层扫描/计算机断层扫描和荧光图像之间具有良好的一致性。在生物分布研究中证实了双标记抗体缀合物在肿瘤中的高特异性和高积累。接种后 1 周观察到最大肿瘤摄取量(分别为 DTPA-G250-IRDye800CW 和 NUH-82 的平均 ± SD 58.5% ± 18.7%和 5.6% ± 2.3%注射剂量/克)。在其他时间点也观察到高肿瘤摄取量。

结论

本研究证明了在透明细胞肾细胞癌模型中使用双标记抗体(111)In-DTPA-G250-IRDye800CW 进行双模态成像的可行性。结果表明,该方法可能可行,可用于术前和术中检测表达碳酸酐酶 IX 的肿瘤、阳性切缘和转移。

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