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Characterization of estrogen‐receptor‐targeted contrast agents in solution, breast cancer cells, and tumors in vivo
Author(s) -
Pais Adi,
Biton Inbal Eti,
Margalit Raanan,
Degani Hadassa
Publication year - 2013
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.24442
Subject(s) - estrogen receptor , in vivo , breast cancer , chemistry , cancer research , immunohistochemistry , tamoxifen , gadolinium , cancer , pathology , medicine , biology , microbiology and biotechnology , organic chemistry
The estrogen receptor (ER) is a major prognostic biomarker of breast cancer, currently determined in surgical specimens by immunohistochemistry. Two new ER‐targeted probes, pyridine‐tetra‐acetate‐Gd chelate (PTA‐Gd) conjugated either to 17β‐estradiol (EPTA‐Gd) or to tamoxifen (TPTA‐Gd), were explored as contrast agents for molecular imaging of ER. In solution, both probes exhibited a micromolar ER binding affinity, fast water exchange rate (∼10 7 s −1 ), and water proton‐relaxivity of 4.7–6.8 mM −1 s −1 . In human breast cancer cells, both probes acted as estrogen agonists and enhanced the water protons T 1 relaxation rate and relaxivity in ER‐positive as compared to ER‐negative cells, with EPTA‐Gd showing a higher ER‐specific relaxivity than TPTA‐Gd. In studies of breast cancer tumors in vivo, EPTA‐Gd induced the highest enhancement in ER‐positive tumors as compared to ER‐negative tumors and muscle tissue, enabling in vivo detection of ER. TPTA‐Gd demonstrated the highest enhancement in muscle tissue indicating nonspecific interaction of this agent with muscle components. The extracellular contrast agents, PTA‐Gd and GdDTPA, showed no difference in the perfusion capacity of ER‐positive and ‐negative tumors confirming the specific interaction of EPTA‐Gd with ER. These findings lay a basis for the molecular imaging of the ER using EPTA‐Gd as a template for further developments. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.