title: Near infrared fluorescent optical imaging for nodal staging.
abstract: Current techniques to assess lymph node metastases in cancer patients include lymphoscintigraphy after administration of a nonspecific radiocolloid in order to locate and resect lymph nodes for pathological examination of harbored cancer cells. Clinical trials involving intradermal or subcutaneous injection of antibody-based nuclear imaging agents have demonstrated the feasibility for target-specific, molecular imaging of cancer-positive lymph nodes. The basis for employing near-infrared (NIR) optical imaging for assessing disease is evidenced by recent work showing functional lymph imaging in mice, swine, and humans. We review antibody-based immunolymphoscintigraphy with an emphasis on the use of trastuzumab (or Herceptin) to target human epidermal growth factor receptor-2 (HER2) overexpressed in some breast cancers. Specifically, we review in vitro and preclinical imaging data from our laboratory that show how the dual-labeled agent ((111)In-DTPA)(n)-trastuzumab-(IRDye800)(m) utilizes the high photon count provided by an NIR fluorescent dye, IRDye 800CW, and the radioactive signal from a gamma emitter, Indium-111, for possible detection of HER2 metastasis in lymph nodes. We show that the accumulation and clearance of ((111)In-DTPA)(n)-trastuzumab-(IRDye800)(m) from the axillary nodes of mice occurs 48 h after intradermal injection into the dorsal aspect of the foot. The requirement for long clearance times from normal, cancer-negative nodes presents challenges for nuclear imaging agents with limited half-lives but does not hamper NIR optical imaging.
authors.affiliation: Baylor College of Medicine, Division of Molecular Imaging, Department of Radiology, Houston, Texas 77030, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Sampath
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Eva M
authors.initials: EM
authors.lastname: Sevick-Muraca
mesh_terms: D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008207:Lymphatic Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013050:Spectrometry, Fluorescence / Q000379:methods*; D013055:Spectrophotometry, Infrared / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D018719:Erb-b2 Receptor Tyrosine Kinases; C524342:(111In-DTPA)n-trastuzumab-(IRDye800)m