Abstract
Objectives-Contrast-enhanced ultrasound (US) and targeted microbubbles have been shown to be advantageous for angiogenesis evaluation and disease staging in cancer. This study explored molecular US imaging of a multitargeted microbubble for assessing the early tumor response to antiangiogenic therapy. Methods-Targetreceptor expression of2LMPbreast cancer cellswasquantified by flow cytometric analysisandcharacterization established with antibodies againstmouseαVβ3- integrin, P-selectin, and vascular endothelial growth factor receptor 2. Tumor-bearing mice (n = 15 per group) underwent contrast-enhanced US imaging of multitargeted microbubbles. Microbubble accumulation was calculated by destruction-replenishment techniquesandtime-intensity curve analysis. On day 0, mice underwent baseline imaging. Next, therapy group mice were injected with a 0.2-mg dose of bevacizumab, and controls received matched saline injections. Imaging was repeated on days 1 and 3. After imaging was completed on day 3, the mice were euthanized and tumors excised. Histologic analysis of microvessel density and intratumoral necrosis was completed on tumor sections. Results-Onday 3 after bevacizumab dosing, a 71.8% change in tumor vasculaturewas shown between the therapy and control groups (P = .01). The therapy group had a 15.4% decrease in tumor vascularity, whereas the control group had a 56.4% increase. Conclusions- MolecularUSimaging of angiogenic markers can detect the early tumor response to drug therapy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1543-1550 |
| Number of pages | 8 |
| Journal | Journal of Ultrasound in Medicine |
| Volume | 31 |
| Issue number | 10 |
| State | Published - Oct 1 2012 |
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Keywords
- Angiogenesis
- Antiangiogenic therapy
- Contrast-enhanced ultrasound
- Microbubbles
- Targeted contrast agent
ASJC Scopus subject areas
- Radiological and Ultrasound Technology
- Radiology Nuclear Medicine and imaging
Cite this
Molecular ultrasound imaging using a targeted contrast agent for assessing early tumor response to antiangiogenic therapy. / Sorace, Anna G.; Saini, Reshu; Mahoney, Marshall; Hoyt, Kenneth.
In: Journal of Ultrasound in Medicine, Vol. 31, No. 10, 01.10.2012, p. 1543-1550.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular ultrasound imaging using a targeted contrast agent for assessing early tumor response to antiangiogenic therapy
AU - Sorace, Anna G.
AU - Saini, Reshu
AU - Mahoney, Marshall
AU - Hoyt, Kenneth
PY - 2012/10/1
Y1 - 2012/10/1
N2 - Objectives-Contrast-enhanced ultrasound (US) and targeted microbubbles have been shown to be advantageous for angiogenesis evaluation and disease staging in cancer. This study explored molecular US imaging of a multitargeted microbubble for assessing the early tumor response to antiangiogenic therapy. Methods-Targetreceptor expression of2LMPbreast cancer cellswasquantified by flow cytometric analysisandcharacterization established with antibodies againstmouseαVβ3- integrin, P-selectin, and vascular endothelial growth factor receptor 2. Tumor-bearing mice (n = 15 per group) underwent contrast-enhanced US imaging of multitargeted microbubbles. Microbubble accumulation was calculated by destruction-replenishment techniquesandtime-intensity curve analysis. On day 0, mice underwent baseline imaging. Next, therapy group mice were injected with a 0.2-mg dose of bevacizumab, and controls received matched saline injections. Imaging was repeated on days 1 and 3. After imaging was completed on day 3, the mice were euthanized and tumors excised. Histologic analysis of microvessel density and intratumoral necrosis was completed on tumor sections. Results-Onday 3 after bevacizumab dosing, a 71.8% change in tumor vasculaturewas shown between the therapy and control groups (P = .01). The therapy group had a 15.4% decrease in tumor vascularity, whereas the control group had a 56.4% increase. Conclusions- MolecularUSimaging of angiogenic markers can detect the early tumor response to drug therapy.
AB - Objectives-Contrast-enhanced ultrasound (US) and targeted microbubbles have been shown to be advantageous for angiogenesis evaluation and disease staging in cancer. This study explored molecular US imaging of a multitargeted microbubble for assessing the early tumor response to antiangiogenic therapy. Methods-Targetreceptor expression of2LMPbreast cancer cellswasquantified by flow cytometric analysisandcharacterization established with antibodies againstmouseαVβ3- integrin, P-selectin, and vascular endothelial growth factor receptor 2. Tumor-bearing mice (n = 15 per group) underwent contrast-enhanced US imaging of multitargeted microbubbles. Microbubble accumulation was calculated by destruction-replenishment techniquesandtime-intensity curve analysis. On day 0, mice underwent baseline imaging. Next, therapy group mice were injected with a 0.2-mg dose of bevacizumab, and controls received matched saline injections. Imaging was repeated on days 1 and 3. After imaging was completed on day 3, the mice were euthanized and tumors excised. Histologic analysis of microvessel density and intratumoral necrosis was completed on tumor sections. Results-Onday 3 after bevacizumab dosing, a 71.8% change in tumor vasculaturewas shown between the therapy and control groups (P = .01). The therapy group had a 15.4% decrease in tumor vascularity, whereas the control group had a 56.4% increase. Conclusions- MolecularUSimaging of angiogenic markers can detect the early tumor response to drug therapy.
KW - Angiogenesis
KW - Antiangiogenic therapy
KW - Contrast-enhanced ultrasound
KW - Microbubbles
KW - Targeted contrast agent
UR - http://www.scopus.com/inward/record.url?scp=84867221880&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867221880&partnerID=8YFLogxK
M3 - Article
C2 - 23011617
AN - SCOPUS:84867221880
VL - 31
SP - 1543
EP - 1550
JO - Journal of Ultrasound in Medicine
JF - Journal of Ultrasound in Medicine
SN - 0278-4297
IS - 10
ER -