Premium
Magnetic resonance molecular imaging of metastatic breast cancer by targeting extradomain‐B fibronectin in the tumor microenvironment
Author(s) -
Han Zheng,
Cheng Han,
Parvani Jenny G.,
Zhou Zhuxian,
Lu ZhengRong
Publication year - 2018
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.26976
Subject(s) - breast cancer , magnetic resonance imaging , fibronectin , medicine , triple negative breast cancer , cancer research , cancer , molecular imaging , ca15 3 , metastasis , metastatic breast cancer , extracellular matrix , pathology , chemistry , biology , radiology , in vivo , microbiology and biotechnology , biochemistry
Purpose Non‐invasive early accurate detection of malignant breast cancer is paramount to the clinical management of the life‐threatening disease. Here, we aim to test a small peptide targeted MRI contrast agent, ZD2‐Gd(HP‐DO3A), specific to an oncoprotein, extradomain‐B fibronectin (EDB‐FN), in the tumor microenvironment for MR molecular imaging of breast cancer. Method EDB‐FN expression in 4T1 and MDA‐MB‐231 cancers was analyzed with quantitative real‐time PCR and western blot. Primary and metastatic triple negative breast cancer mouse models were developed using 4T1 and MDA‐MB‐231 cells. Contrast‐enhanced MRI was carried out to evaluate the use of ZD2‐Gd(HP‐DO3A) in detecting 4T1 and MDA‐MB‐231 primary and metastatic tumors. Results EDB‐FN was abundantly expressed in the extracellular matrix (ECM) of both the primary and metastatic TNBC tumors. In T 1 ‐weighted MRI, ZD2‐Gd(HP‐DO3A) generated superior contrast enhancement in primary TNBC tumors than a nonspecific clinical agent Gd(HP‐DO3A), during 30 min after contrast injection. ZD2‐Gd(HP‐DO3A) also produced a significant increase in contrast‐to‐noise ratio (CNR) of TNBC metastases, enabling sensitive localization and delineation of metastases that occulted in non‐contrast‐enhanced or Gd(HP‐DO3A)‐enhanced MRI. Conclusions These findings potentiate the use of ZD2‐Gd(HP‐DO3A) for MR molecular imaging of malignant breast cancers to improve the healthcare of breast cancer patients. Magn Reson Med 79:3135–3143, 2018. © 2017 International Society for Magnetic Resonance in Medicine.