Abstract 4216: Experimental imaging in orthotopic xenograft models of renal cell carcinoma: comparative evaluation of high-resolution ultrasonography, in vivo micro-CT, and 9.4T MRI
Authors: Linxweiler Johannes , Körbel Christina , Müller Andreas , Jung Volker , Jüngel Eva , Siemer Stefan , Stöckle Michael , Junker Kerstin , Menger Michael D. , Saar Matthias 
Published: July 2016

Abstract
Introductory Sentence
Orthotopic xenografts are increasingly used as preclinical in-vivo models for the study of renal cell carcinoma (RCC). However, monitoring of these tumors requires sophisticated imaging techniques. In this study, we comparatively evaluated modern small animal imaging tools like high-resolution 3D-ultrasonography (3D-US), contrast-enhanced in-vivo micro-CT (CE-CT) and 9,4T MRI (MRI) to non-invasively monitor tumor growth and progression in an orthotopic RCC xenograft model.
Material and Methods
106 CAKI-1 cells were injected under the renal capsule of 18 Balb/c-nude mice. Every 14 days from week 4 imaging was performed by CE-CT and 3D-US. 10 weeks after tumor cell inoculation, all animals additionally underwent multiparametric MRI (T1, T2, T2*, DWI). At autopsy, tumor volumes were determined using a caliper and compared to in-vivo imaging results. CE-CT, MRI and 3D-US were evaluated regarding tumor detection, analysis of tumor volume, radiographic imaging properties and examination time. Finally, similar experiments were performed with the RCC cell lines KTCTL30 (n = 2) and 786-0 (n = 1) to test their applicability for the orthotopic xenograft model.
Results
Tumors were detected in 16/18 animals (89%) 4 weeks after orthotopic inoculation. All methods enabled to adequately visualize orthotopic tumors and to display their growth over time. While the tumors had a homogenously radiolucent signal in CT scans, sonography and MRI were better able to visualized intratumoral structures (e.g. solid areas or intratumoral bleedings) and surrounding soft tissue. CT had the best spatial resolution, followed by 3D-US and MRI. The median examination time was 4.8min per 3D-US, 12.5min per CT and 37.9min per MRI, respectively. Of interest, tumor volumes determined by KM-CT and ultrasonography showed strong correlation with each other (n = 85, R = 0.985) as well as with caliper measurements at autopsy (CT: n = 16. R = 0.922; sonography: n = 16, R = 0.934). Similarly, tumor volumes measured with T2-weighted MRI correlated well with those determined by CT, sonography and caliper. No side effects due to radiation exposure were observed. Mice inoculated with KTCTL30 cells developed partly cystic, partly solid tumors. 786-O cells yielded purely solid, exponentially growing tumors.
Conclusion
All three imaging modalities are feasible tools for the non-invasive monitoring of orthotopic tumor growth and show excellent correlation with each other. While sonography allows for a fast analysis of tumor volume with excellent resolution and no radiation exposure, MRI provides the best visualization of soft tissue and can give information about tumor biology when acquiring additional sequences. CT has the best spatial resolution of all methods and enables simultaneous screening for bone and lung metastases but relies on the use of contrast agent and ionizing radiation.
Citation Format: Johannes Linxweiler, Christina Körbel, Andreas Müller, Volker Jung, Eva Jüngel, Stefan Siemer, Michael Stöckle, Kerstin Junker, Michael D. Menger, Matthias Saar. Experimental imaging in orthotopic xenograft models of renal cell carcinoma: comparative evaluation of high-resolution ultrasonography, in vivo micro-CT, and 9.4T MRI. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4216.