title: A mammaglobin-A targeting agent for noninvasive detection of breast cancer metastasis in lymph nodes.
abstract: Pathologic axillary lymph node (ALN) status is an important prognostic factor for staging breast cancer. Currently, status is determined by histopathology following surgical excision of sentinel lymph node(s), which is an invasive, time consuming, and costly procedure with potential morbidity to the patient. Here, we describe an imaging platform for noninvasive assessment of ALN status, eliminating the need for surgical examination of patients to rule out nodal involvement. A targeted imaging probe (MamAb-680) was developed by conjugation of a mammaglobin-A-specific monoclonal antibody to a near-infrared fluorescent dye. Using DNA and tissue microarray, mammaglobin-A was validated as a cell-surface target that is expressed in ALN-positive patient samples but is not expressed in normal lymph nodes. In vivo selectivity was determined by i.v. injection of MamAb-680 into mice with mammaglobin-A-positive and -negative mammary fat pad (MFP) tumors; and by peritumoral MFP injection of the targeted imaging probe in mice with spontaneous ALN metastases. Fluorescence imaging showed that probe was only retained in positive tumors and metastases. As few as 1,000 cells that endogenously express mammaglobin-A were detected in ALN, indicating high sensitivity of this method. Translation of this approach offers considerable potential as a noninvasive clinical strategy to stage breast cancer.
authors.affiliation: Department of Functional & Molecular Imaging, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.
authors.forename: Narges K
authors.initials: NK
authors.lastname: Tafreshi
authors.forename: Steven A
authors.initials: SA
authors.lastname: Enkemann
authors.forename: Marilyn M
authors.initials: MM
authors.lastname: Bui
authors.forename: Mark C
authors.initials: MC
authors.lastname: Lloyd
authors.forename: Dominique
authors.initials: D
authors.lastname: Abrahams
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Huynh
authors.forename: Jongphil
authors.initials: J
authors.lastname: Kim
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Grobmyer
authors.forename: W Bradford
authors.initials: WB
authors.lastname: Carter
authors.forename: Josef
authors.initials: J
authors.lastname: Vagner
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gillies
authors.forename: David L
authors.initials: DL
authors.lastname: Morse
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics; D000918:Antibody Specificity; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D003952:Diagnostic Imaging / Q000379:methods; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D060785:Mammaglobin A; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D014183:Transplantation, Heterologous; D014598:Uteroglobin / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D005456:Fluorescent Dyes; D018796:Immunoconjugates; D060785:Mammaglobin A; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C556448:SCGB2A2 protein, human; D014598:Uteroglobin