A mammaglobin-A targeting agent for noninvasive detection of breast cancer metastasis in lymph nodes

Narges K. Tafreshi, Steven A. Enkemann, Marilyn M. Bui, Mark C. Lloyd, Dominique Abrahams, Amanda S. Huynh, Jongphil Kim, Stephen R. Grobmyer, W. Bradford Carter, Josef Vagner, Robert J. Gillies, David L. Morse

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1050-1059
Number of pages10
JournalCancer Research
Volume71
Issue number3
DOIs
StatePublished - Feb 1 2011

Fingerprint

Mammaglobin A
Lymph Nodes
Breast Neoplasms
Neoplasm Metastasis
Adipose Tissue
Breast
Injections
Optical Imaging
Oligonucleotide Array Sequence Analysis
Fluorescent Dyes
Neoplasms
Monoclonal Antibodies
Morbidity

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tafreshi, N. K., Enkemann, S. A., Bui, M. M., Lloyd, M. C., Abrahams, D., Huynh, A. S., ... Morse, D. L. (2011). A mammaglobin-A targeting agent for noninvasive detection of breast cancer metastasis in lymph nodes. Cancer Research, 71(3), 1050-1059. https://doi.org/10.1158/0008-5472.CAN-10-3091

A mammaglobin-A targeting agent for noninvasive detection of breast cancer metastasis in lymph nodes. / Tafreshi, Narges K.; Enkemann, Steven A.; Bui, Marilyn M.; Lloyd, Mark C.; Abrahams, Dominique; Huynh, Amanda S.; Kim, Jongphil; Grobmyer, Stephen R.; Carter, W. Bradford; Vagner, Josef; Gillies, Robert J.; Morse, David L.

In: Cancer Research, Vol. 71, No. 3, 01.02.2011, p. 1050-1059.

Research output: Contribution to journalArticle

Tafreshi, NK, Enkemann, SA, Bui, MM, Lloyd, MC, Abrahams, D, Huynh, AS, Kim, J, Grobmyer, SR, Carter, WB, Vagner, J, Gillies, RJ & Morse, DL 2011, 'A mammaglobin-A targeting agent for noninvasive detection of breast cancer metastasis in lymph nodes', Cancer Research, vol. 71, no. 3, pp. 1050-1059. https://doi.org/10.1158/0008-5472.CAN-10-3091
Tafreshi, Narges K. ; Enkemann, Steven A. ; Bui, Marilyn M. ; Lloyd, Mark C. ; Abrahams, Dominique ; Huynh, Amanda S. ; Kim, Jongphil ; Grobmyer, Stephen R. ; Carter, W. Bradford ; Vagner, Josef ; Gillies, Robert J. ; Morse, David L. / A mammaglobin-A targeting agent for noninvasive detection of breast cancer metastasis in lymph nodes. In: Cancer Research. 2011 ; Vol. 71, No. 3. pp. 1050-1059.
@article{6edd650d953e4dc9b133067b65894f05,
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.",
author = "Tafreshi, {Narges K.} and Enkemann, {Steven A.} and Bui, {Marilyn M.} and Lloyd, {Mark C.} and Dominique Abrahams and Huynh, {Amanda S.} and Jongphil Kim and Grobmyer, {Stephen R.} and Carter, {W. Bradford} and Josef Vagner and Gillies, {Robert J.} and Morse, {David L.}",
year = "2011",
month = "2",
day = "1",
doi = "10.1158/0008-5472.CAN-10-3091",
language = "English (US)",
volume = "71",
pages = "1050--1059",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

TY - JOUR

T1 - A mammaglobin-A targeting agent for noninvasive detection of breast cancer metastasis in lymph nodes

AU - Tafreshi, Narges K.

AU - Enkemann, Steven A.

AU - Bui, Marilyn M.

AU - Lloyd, Mark C.

AU - Abrahams, Dominique

AU - Huynh, Amanda S.

AU - Kim, Jongphil

AU - Grobmyer, Stephen R.

AU - Carter, W. Bradford

AU - Vagner, Josef

AU - Gillies, Robert J.

AU - Morse, David L.

PY - 2011/2/1

Y1 - 2011/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79551549744&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79551549744&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-10-3091

DO - 10.1158/0008-5472.CAN-10-3091

M3 - Article

VL - 71

SP - 1050

EP - 1059

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 3

ER -