Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, Texas, USA.
Prostate. 2012 Feb 1;72(2):129-46. doi: 10.1002/pros.21413. Epub 2011 May 2.
Methods to detect lymph node (LN) metastases in prostate cancer (PCa) are limited. Pelvic LN dissection is commonly performed during prostatectomy, but often followed by morbid complications. More refined methods for detecting LN invasion are needed.
We developed a dual-labeled targeting agent having a near-infrared (NIR) fluorophore for intraoperative guidance, and a conventional radiotracer for detection of LN metastasis. Nu/Nu mice were orthotopically implanted with DsRed-expressing human PCa (PC3) cells. Antibody (Ab) specific for epithelial cell adhesion molecule was conjugated to DOTA, IRDye 800CW, and radiolabeled with (64) Cu. Dual-labeled Ab was administered intravenously at 10-12 weeks post-implantation, and positron emission tomography/computed tomography (PET/CT) and fluorescence imaging were performed within 18-24 hr.
Metastasis to lumbar LNs was detected by DsRed fluorescence imaging, as well as pathology, in 75% of mice having pathology-confirmed primary prostate tumors. These metastases were also detected by NIR fluorescence imaging. In some cases, metastases to sciatic, medial, renal, and axillary nodes were also detected. For all LNs examined, no significant differences were found between the percentages of metastases detected by NIR imaging (63%) and µPET/CT (64%) (P = 0.93), or between those detected by DsRed imaging (25%) and pathological examination (19%) (P = 0.12).
This study demonstrates that a multimodality contrast agent is useful for early detection of metastatic disease, and has applications for intraoperative PCa treatment. Further agent optimization is necessary to enhance specificity, and provide validation for prostate and other LN metastasizing epithelial cancers.
目前用于检测前列腺癌（PCa）淋巴结（LN）转移的方法有限。在前列腺切除术中通常进行盆腔 LN 清扫，但常伴有严重的并发症。因此，需要更精细的方法来检测 LN 侵犯。
我们开发了一种双标记靶向剂，具有用于术中指导的近红外（NIR）荧光团和用于检测 LN 转移的常规放射性示踪剂。将表达 DsRed 的人前列腺癌细胞（PC3）原位植入 Nu/Nu 小鼠。针对上皮细胞黏附分子的抗体与 DOTA、IRDye 800CW 缀合，并与（64）Cu 放射性标记。在植入后 10-12 周静脉内给予双标记 Ab，在 18-24 小时内进行正电子发射断层扫描/计算机断层扫描（PET/CT）和荧光成像。
在经病理证实有原发性前列腺肿瘤的 75%小鼠中，通过 DsRed 荧光成像以及病理学检测到腰椎 LN 转移。这些转移也可通过 NIR 荧光成像检测到。在某些情况下，还可检测到坐骨、内侧、肾和腋窝淋巴结的转移。对于所有检查的 LN，NIR 成像（63%）和 µPET/CT（64%）（P = 0.93）或 DsRed 成像（25%）和病理检查（19%）（P = 0.12）检测到的转移百分比之间无显著差异。
本研究表明，多模态对比剂可用于早期检测转移性疾病，并且可用于前列腺癌的术中治疗。需要进一步优化该试剂，以增强特异性，并为前列腺和其他 LN 转移的上皮性癌症提供验证。
