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Imaging of brain tumors with paramagnetic vesicles targeted to phosphatidylserine
Author(s) -
Winter Patrick M.,
Pearce John,
Chu Zhengtao,
McPherson Christopher M.,
Takigiku Ray,
Lee JingHuei,
Qi Xiaoyang
Publication year - 2015
Publication title -
journal of magnetic resonance imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.563
H-Index - 160
eISSN - 1522-2586
pISSN - 1053-1807
DOI - 10.1002/jmri.24654
Subject(s) - vesicle , phosphatidylserine , in vivo , gadolinium , pathology , glioma , chemistry , medicine , cancer research , biology , biochemistry , phospholipid , microbiology and biotechnology , organic chemistry , membrane
Purpose To investigate paramagnetic saposin C and dioleylphosphatidylserine (SapC‐DOPS) vesicles as a targeted contrast agent for imaging phosphatidylserine (PS) expressed by glioblastoma multiforme (GBM) tumors. Materials and Methods Gd‐DTPA‐BSA/SapC‐DOPS vesicles were formulated, and the vesicle diameter and relaxivity were measured. Targeting of Gd‐DTPA‐BSA/SapC‐DOPS vesicles to tumor cells in vitro and in vivo was compared with nontargeted paramagnetic vesicles (lacking SapC). Mice with GBM brain tumors were imaged at 3, 10, 20, and 24 h postinjection to measure the relaxation rate (R1) in the tumor and the normal brain. Results The mean diameter of vesicles was 175 nm, and the relaxivity at 7 Tesla was 3.32 (s*mM) −1 relative to the gadolinium concentration. Gd‐DTPA‐BSA/SapC‐DOPS vesicles targeted cultured cancer cells, leading to an increased R1 and gadolinium level in the cells. In vivo, Gd‐DTPA‐BSA/SapC‐DOPS vesicles produced a 9% increase in the R1 of GBM brain tumors in mice 10 h postinjection, but only minimal changes (1.2% increase) in the normal brain. Nontargeted paramagnetic vesicles yielded minimal change in the tumor R1 at 10 h postinjection (1.3%). Conclusion These experiments demonstrate that Gd‐DTPA‐BSA/SapC‐DOPS vesicles can selectively target implanted brain tumors in vivo, providing noninvasive mapping of the cancer biomarker PS. J. Magn. Reson. Imaging 2015;41:1079–1087 . © 2014 Wiley Periodicals, Inc .