Imaging of nodal metastases in prostate cancer using a dual-labeled agent

Objectives Detection methods for nodal metastasis in prostate cancer are limited. Often during prostectomy, extended pelvic lymph node (LN) dissection is performed and uninvolved LNs may be removed. Lymphedema can result as a consequence of LN resection. In this study, we developed a dual-labeled targeting agent having a near-infrared (NIR) fluorophore for guidance intraoperatively to detect nodal involvement, and a radiotracer for conventional detection.

Methods Nu/Nu mice were orthotopically implanted with dsRed-expressing PC3 cells and imaged longitudinally for detection of fluorescent cancer cells. For functional imaging, an antibody (Ab) specific for epithelial cell adhesion molecule (EpCAM), which is over-expressed in prostate cancer, was conjugated to DOTA and labeled with IRDye 800CW. The agent was further labeled with 64Cu at >97% radiochemical yield and purified by size exclusion chromatography. At 10 weeks post-implantation, PET/CT and NIR imaging were performed at 12 hr post-injection of dual-labeled Ab (75-150 µCi/mouse).

Results Metastasis to lumbar or axillary LNs was detected by dsRed or NIR fluorescence imaging in >80% of mice having prostate tumors. PET/CT imaging detected cancer cells in some of these mice. In certain cases, cancer cell detection was masked by high radionuclide uptake in the bladder.

Conclusions Multimodality imaging is useful for early detection of metastatic disease, and also has applications for intraoperative cancer treatment. This study demonstrated that nodal metastases can be detected using a dual-labeled anti-EpCAM Ab and fluorescence imaging in a prostate cancer mouse model. Further characterization of the agent in other metastatic tumor models is required to demonstrate sensitivity and provide validation