Imaging the development of functional tumour vasculature in vivo in preclinical models


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Gemma Marston1, Nicola Ingram1, Mark Hull1, Alex Markham1, Pam Jones1, P. Louise Coletta1
1University of Leeds, Leeds, UK

Background

Angiogenesis is essential for tumours to grow beyond a few millimetres in size and to metastasise, making it an attractive target for both cancer imaging and therapeutic intervention. Contrast enhanced high-frequency ultrasound (CE HFUS) enables longitudinal studies in mouse models and can be used to investigate both qualitative and quantitative changes in tumour vasculature including tumour blood flow and perfusion. We have developed CE HFUS protocols to characterise the development of functional tumour vasculature in vivo in a murine xenograft model of colorectal cancer.

Method

10 female CD1 Nu/Nu mice implanted with SW480 human colorectal cancer cell xenografts were imaged with CE HFUS 7 times between day 7 and day 28 of tumour growth using the VisualSonics Vevo 770 system. At each time point a single bolus of microbubbles was injected using a syringe driver into the tail vein during 2D CE HFUS imaging, with the wash-in data loops captured prior to 3D CE HFUS imaging.

Results

Time intensity curves were generated post-acquisition and used to determine perfusion kinetics and vascular data. Tumour vascular space and tumour volume were calculated from 3D CE HFUS images. This showed that the percentage tumour vascular space decreased significantly as the tumour volume increased. Furthermore, smaller tumours had both faster rates of blood flow and significantly higher maximum levels of vascular perfusion than larger tumours.

Conclusion

This study shows that CE HFUS is a powerful tool for analysis of tumour vascular development in vivo and provides a relatively non-invasive method to assess development of anti-angiogenic therapies and response to treatment in pre-clinical trials.