Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands; and Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands; and Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
J Nucl Med. 2014 Jun;55(6):1035-40. doi: 10.2967/jnumed.114.137356. Epub 2014 Apr 21.
Near-infrared dye-tagged antibodies can be used for the sensitive detection of tumor tissue in vivo. Surgery for clear-cell renal cell carcinoma (ccRCC) might benefit from the use of optical imaging to facilitate the intraoperative detection of carbonic anhydrase IX (CAIX)-expressing tumor lesions with chimeric monoclonal antibody (mAb) girentuximab, which has been shown to have excellent imaging capabilities for ccRCC. Here we studied the potential of fluorescence imaging to detect ccRCC tumors in nude mice with RCC xenografts by using mAb girentuximab conjugated with IRDye800CW; SPECT imaging was used as a reference.
Groups of athymic BALB/c mice with subcutaneous CAIX-positive SK-RC-52 ccRCC tumors were injected intravenously with (125)I-labeled girentuximab-IRDye800CW or (125)I-labeled girentuximab. For determination of the specificity of the accumulation of the anti-CAIX antibody conjugate in ccRCC, separate groups of mice bearing a CAIX-positive tumor (SK-RC-52) and a CAIX-negative tumor (SK-RC-59) received (125)I-girentuximab-IRDye800CW or (125)I-labeled MOPC21-IRDye800CW (control mAb). Optical images and micro-SPECT images were acquired until 3 d after injection. Mice were euthanized after the last imaging session, and the biodistribution of the radiolabeled antibody preparations was determined.
Optical imaging and micro-SPECT imaging at 1 d after the injection of (125)I-girentuximab-IRDye800CW showed clear delineation of the CAIX-expressing ccRCC xenografts, and image contrast improved with time. Fluorescence imaging and biodistribution studies showed high and specific uptake of (125)I-girentuximab-IRDye800CW in CAIX-positive ccRCC xenografts (SK-RC-52, 31.5 ± 9.6 percentage injected dose per gram [%ID/g] at 72 h after injection). Tumor uptake was specific, as very low uptake of (125)I-girentuximab-IRDye800CW was noted in the CAIX-negative SK-RC-59 tumor (4.1 ± 1.5 %ID/g), and no uptake of (125)I-MOPC21-IRDye800CW (control mAb) was noted in the CAIX-positive SK-RC-52 tumor (1.2 ± 0.1 %ID/g).
Subcutaneous CAIX-expressing ccRCC xenografts were visualized by optical imaging with (125)I-girentuximab-IRDye800CW. Optical images showed good concordance with micro-SPECT images. The accumulation of (125)I-girentuximab-IRDye800CW in ccRCC tumors was high and specific. Girentuximab-IRDye800CW potentially could be used for the intraoperative detection of CAIX-expressing tumors and the assessment of residual tumor in resection margins or metastatic lesions in patients with ccRCC.
使用与近红外染料标记的抗体偶联的 IRDye800CW 对表达碳酸酐酶 IX（CAIX）的肾透明细胞癌（ccRCC）肿瘤进行体内荧光检测，探讨荧光成像在荷肾透明细胞癌裸鼠模型中的应用。方法：将 CAIX 阳性的 SK-RC-52 ccRCC 皮下移植瘤的裸鼠分组，静脉注射（125）I 标记的 girentuximab-IRDye800CW 或（125）I 标记的 girentuximab。为了确定 CAIX 抗体偶联物在 ccRCC 中特异性聚集的特异性，用 CAIX 阳性肿瘤（SK-RC-52）和 CAIX 阴性肿瘤（SK-RC-59）分别接受（125）I-girentuximab-IRDye800CW 或（125）I-标记的 MOPC21-IRDye800CW（对照 mAb）。在注射后 1 天进行光学和微 SPECT 图像采集，直到 3 天。最后一次成像后处死小鼠，测定放射性标记抗体的分布。结果：注射（125）I-girentuximab-IRDye800CW 1 天后，光学和微 SPECT 成像可清晰显示 CAIX 表达的 ccRCC 异种移植瘤，且随时间推移图像对比度增加。荧光成像和生物分布研究表明，CAIX 阳性 ccRCC 异种移植瘤（SK-RC-52）中（125）I-girentuximab-IRDye800CW 的摄取量高且特异性强（注射后 72 小时为 31.5±9.6% 注入剂量/克 [%ID/g]）。肿瘤摄取具有特异性，因为 CAIX 阴性 SK-RC-59 肿瘤中的（125）I-girentuximab-IRDye800CW 摄取量非常低（4.1±1.5%ID/g），而 CAIX 阳性 SK-RC-52 肿瘤中未摄取（125）I-MOPC21-IRDye800CW（对照 mAb）（1.2±0.1%ID/g）。结论：用（125）I-girentuximab-IRDye800CW 进行光学成像可检测到皮下表达 CAIX 的 ccRCC 异种移植瘤。光学图像与微 SPECT 图像具有良好的一致性。（125）I-girentuximab-IRDye800CW 在 ccRCC 肿瘤中的积累量高且具有特异性。Girentuximab-IRDye800CW 可能可用于术中检测表达 CAIX 的肿瘤，并评估患者肾透明细胞癌切除边缘的残留肿瘤或转移性病变。
