TY - JOUR
T1 - Selective Imaging of Malignant Ascites in a Mouse Model of Peritoneal Metastasis Using in Vivo Dynamic Nuclear Polarization-Magnetic Resonance Imaging
AU - Eto, Hinako
AU - Hyodo, Fuminori
AU - Nakano, Kenji
AU - Utsumi, Hideo
N1 - Funding Information:
This work was supported by Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and by a Development of Advanced Measurement and Analysis Systems grant from the Japan Science and Technology Agency (H.U.). This work was also supported by KAKENHI Grant Numbers 22249003 (H.U.), 25253005 (H.U.), 25713004 (F.H.), and 26670016 (K.N.) from the Japan Society for the Promotion of Science.
Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/2/16
Y1 - 2016/2/16
N2 - The presence of malignant ascites in advanced cancer patients is associated with both a poor prognosis and quality of life with a risk of abdominal infection and sepsis. Contemporary noninvasive visualization methods such as ultrasound, computed tomography, and magnetic resonance imaging (MRI) often struggle to differentiate malignant ascites from surrounding tissues. This study aimed to determine the utility of selective H2O imaging in the abdominal cavity with a free radical probe and deuterium oxide (D2O) contrast agent using in vivo dynamic nuclear polarization-MRI (DNP-MRI). Phantom imaging experiments established a linear relationship between H2O volume and image intensity using in vivo DNP-MRI. Similar results were obtained when the radical-D2O probe was used to determine selective and spatial information on H2O in vivo, modeled by the injection of saline into the abdominal cavity of mice. To demonstrate the utility of this method for disease, malignant ascites in peritoneal metastasis animal model was selected as one of the typical examples. In vivo DNP-MRI of peritoneal metastasis animal model was performed 7-21 days after intraperitoneal injection of luciferase, stably expressing the human pancreatic carcinoma (SUIT-2). The image intensity with increasing malignant ascites was significantly increased at days 7, 16, and 21. This increase corresponded to in vivo tumor progression, as measured by bioluminescent imaging. These results suggest that H2O signal enhancement in DNP-MRI using radical-D2O contrast is positively associated with the progression of dissemination and could be a useful biomarker for malignant ascites with cancer metastasis.
AB - The presence of malignant ascites in advanced cancer patients is associated with both a poor prognosis and quality of life with a risk of abdominal infection and sepsis. Contemporary noninvasive visualization methods such as ultrasound, computed tomography, and magnetic resonance imaging (MRI) often struggle to differentiate malignant ascites from surrounding tissues. This study aimed to determine the utility of selective H2O imaging in the abdominal cavity with a free radical probe and deuterium oxide (D2O) contrast agent using in vivo dynamic nuclear polarization-MRI (DNP-MRI). Phantom imaging experiments established a linear relationship between H2O volume and image intensity using in vivo DNP-MRI. Similar results were obtained when the radical-D2O probe was used to determine selective and spatial information on H2O in vivo, modeled by the injection of saline into the abdominal cavity of mice. To demonstrate the utility of this method for disease, malignant ascites in peritoneal metastasis animal model was selected as one of the typical examples. In vivo DNP-MRI of peritoneal metastasis animal model was performed 7-21 days after intraperitoneal injection of luciferase, stably expressing the human pancreatic carcinoma (SUIT-2). The image intensity with increasing malignant ascites was significantly increased at days 7, 16, and 21. This increase corresponded to in vivo tumor progression, as measured by bioluminescent imaging. These results suggest that H2O signal enhancement in DNP-MRI using radical-D2O contrast is positively associated with the progression of dissemination and could be a useful biomarker for malignant ascites with cancer metastasis.
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U2 - 10.1021/acs.analchem.5b04821
DO - 10.1021/acs.analchem.5b04821
M3 - Article
C2 - 26796949
AN - SCOPUS:84958259485
VL - 88
SP - 2021
EP - 2027
JO - Analytical Chemistry
JF - Analytical Chemistry
SN - 0003-2700
IS - 4
ER -