title: Imaging prostate cancer lymph node metastases with a multimodality contrast agent.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Hall
authors.forename: Sunkuk
authors.initials: S
authors.lastname: Kwon
authors.forename: Holly
authors.initials: H
authors.lastname: Robinson
authors.forename: Pier-Anne
authors.initials: PA
authors.lastname: Lachance
authors.forename: Ali
authors.initials: A
authors.lastname: Azhdarinia
authors.forename: Ranjani
authors.initials: R
authors.lastname: Ranganathan
authors.forename: Roger E
authors.initials: RE
authors.lastname: Price
authors.forename: Wenyaw
authors.initials: W
authors.lastname: Chan
authors.forename: Eva M
authors.initials: EM
authors.lastname: Sevick-Muraca
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics; D003301:Copper Radioisotopes / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D000071858:Epithelial Cell Adhesion Molecule; D006573:Heterocyclic Compounds, 1-Ring / Q000493:pharmacokinetics; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods; D064847:Multimodal Imaging / Q000379:methods; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D012372:ROC Curve; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D003287:Contrast Media; D003301:Copper Radioisotopes; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D006573:Heterocyclic Compounds, 1-Ring; C427728:IRDye800; D007211:Indoles; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid