Abstract
Objectives-The purpose of this study was to quantitatively assess the contrast kinetics of vascular endothelial growth factor receptor 2 (VEGFR2)-targeted microbubbles (BR55; Bracco Suisse, Geneva, Switzerland) compared to clinically used microbubbles (SonoVue; Bracco SpA, Milan, Italy) in both normal liver and human hepatocellular carcinoma xenograft tumors in mice. Methods-Microbubbles were injected intravenously into healthy mice (n = 5) and mice bearing hepatocellular carcinoma xenograft tumors (n = 10). Cine loops of contrast enhancement in normal liver and the tumors were acquired for 10 minutes. Quantitative perfusion parameters were derived by fitting time-intensity curves using a dedicated mathematical model combining a bolus function and a ramp function. Immunohistochemical examinations were also performed for normal liver and tumor specimens to determine the level of VEGFR2 expression. Results-The peak contrast enhancement observed in normal liver with BR55 was comparable to that with SonoVue, whereas a significant difference was observed in latephase enhancement at 10 minutes (ramp slope: P<.01). In the tumor model, SonoVue was rapidly cleared from the circulation, without any noticeable binding in the tumor, whereas BR55 showed a gradual decline, resulting in a longer wash-out period (mean transit time: P <.01). Immunohistochemical examinations showed that intratumoral vascular endothelial cells had sparse and weak VEGFR2 expression, whereas the sinusoidal capillaries in normal liver had much more diffuse and much stronger expression. Conclusions-Our results suggest that BR55 accurately reflects the VEGFR2 status in human hepatocellular carcinoma xenograft tumors. We showed that quantification applied to molecular ultrasound imaging may provide an objective method for measuring the degree of microbubble binding.
| Original language | English |
|---|---|
| Pages (from-to) | 1909-1916 |
| Number of pages | 8 |
| Journal | Journal of Ultrasound in Medicine |
| Volume | 31 |
| Issue number | 12 |
| Publication status | Published - Dec 1 2012 |
| Externally published | Yes |
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Keywords
- Angiogenesis
- BR55
- Hepatocellular carcinoma
- Molecular ultrasound
- Vascular endothelial growth factor receptor 2
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging
- Radiological and Ultrasound Technology
- Medicine(all)
Cite this
Quantification in molecular ultrasound imaging a comparative study in mice between healthy liver and a human hepatocellular carcinoma xenograft. / Sugimoto, Katsutoshi; Moriyasu, Fuminori; Negishi, Yoichi; Hamano, Nobuhito; Oshiro, Hisashi; Rognin, Nicolas G.; Yoshida, Tetsuya; Kamiyama, Naohisa; Aramaki, Yukihiko; Imai, Yasuharu.
In: Journal of Ultrasound in Medicine, Vol. 31, No. 12, 01.12.2012, p. 1909-1916.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Quantification in molecular ultrasound imaging a comparative study in mice between healthy liver and a human hepatocellular carcinoma xenograft
AU - Sugimoto, Katsutoshi
AU - Moriyasu, Fuminori
AU - Negishi, Yoichi
AU - Hamano, Nobuhito
AU - Oshiro, Hisashi
AU - Rognin, Nicolas G.
AU - Yoshida, Tetsuya
AU - Kamiyama, Naohisa
AU - Aramaki, Yukihiko
AU - Imai, Yasuharu
PY - 2012/12/1
Y1 - 2012/12/1
N2 - Objectives-The purpose of this study was to quantitatively assess the contrast kinetics of vascular endothelial growth factor receptor 2 (VEGFR2)-targeted microbubbles (BR55; Bracco Suisse, Geneva, Switzerland) compared to clinically used microbubbles (SonoVue; Bracco SpA, Milan, Italy) in both normal liver and human hepatocellular carcinoma xenograft tumors in mice. Methods-Microbubbles were injected intravenously into healthy mice (n = 5) and mice bearing hepatocellular carcinoma xenograft tumors (n = 10). Cine loops of contrast enhancement in normal liver and the tumors were acquired for 10 minutes. Quantitative perfusion parameters were derived by fitting time-intensity curves using a dedicated mathematical model combining a bolus function and a ramp function. Immunohistochemical examinations were also performed for normal liver and tumor specimens to determine the level of VEGFR2 expression. Results-The peak contrast enhancement observed in normal liver with BR55 was comparable to that with SonoVue, whereas a significant difference was observed in latephase enhancement at 10 minutes (ramp slope: P<.01). In the tumor model, SonoVue was rapidly cleared from the circulation, without any noticeable binding in the tumor, whereas BR55 showed a gradual decline, resulting in a longer wash-out period (mean transit time: P <.01). Immunohistochemical examinations showed that intratumoral vascular endothelial cells had sparse and weak VEGFR2 expression, whereas the sinusoidal capillaries in normal liver had much more diffuse and much stronger expression. Conclusions-Our results suggest that BR55 accurately reflects the VEGFR2 status in human hepatocellular carcinoma xenograft tumors. We showed that quantification applied to molecular ultrasound imaging may provide an objective method for measuring the degree of microbubble binding.
AB - Objectives-The purpose of this study was to quantitatively assess the contrast kinetics of vascular endothelial growth factor receptor 2 (VEGFR2)-targeted microbubbles (BR55; Bracco Suisse, Geneva, Switzerland) compared to clinically used microbubbles (SonoVue; Bracco SpA, Milan, Italy) in both normal liver and human hepatocellular carcinoma xenograft tumors in mice. Methods-Microbubbles were injected intravenously into healthy mice (n = 5) and mice bearing hepatocellular carcinoma xenograft tumors (n = 10). Cine loops of contrast enhancement in normal liver and the tumors were acquired for 10 minutes. Quantitative perfusion parameters were derived by fitting time-intensity curves using a dedicated mathematical model combining a bolus function and a ramp function. Immunohistochemical examinations were also performed for normal liver and tumor specimens to determine the level of VEGFR2 expression. Results-The peak contrast enhancement observed in normal liver with BR55 was comparable to that with SonoVue, whereas a significant difference was observed in latephase enhancement at 10 minutes (ramp slope: P<.01). In the tumor model, SonoVue was rapidly cleared from the circulation, without any noticeable binding in the tumor, whereas BR55 showed a gradual decline, resulting in a longer wash-out period (mean transit time: P <.01). Immunohistochemical examinations showed that intratumoral vascular endothelial cells had sparse and weak VEGFR2 expression, whereas the sinusoidal capillaries in normal liver had much more diffuse and much stronger expression. Conclusions-Our results suggest that BR55 accurately reflects the VEGFR2 status in human hepatocellular carcinoma xenograft tumors. We showed that quantification applied to molecular ultrasound imaging may provide an objective method for measuring the degree of microbubble binding.
KW - Angiogenesis
KW - BR55
KW - Hepatocellular carcinoma
KW - Molecular ultrasound
KW - Vascular endothelial growth factor receptor 2
UR - http://www.scopus.com/inward/record.url?scp=84871821612&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871821612&partnerID=8YFLogxK
M3 - Article
VL - 31
SP - 1909
EP - 1916
JO - Journal of Ultrasound in Medicine
JF - Journal of Ultrasound in Medicine
SN - 0278-4297
IS - 12
ER -