Abstract 4321: A four-pronged imaging approach to characterization of bone metastasis in mouse models
Authors: Lister Deanne , Woolliscroft Michael , Kaimal Vinod , Leopold Wilbur R. , McConville Patrick 
Published: February 2011

Introduction: The process of bone metastasis involves both osteoblastic and resorptive components and is a common feature of both prostate and breast cancers. The ability to visualize and quantify the early stages of bone involvement in mouse models of bone metastasis would provide a platform for development of new agents targeted at inhibition or treatment of bone metastases. Two approaches that stand to enable this are 18F-NaF PET and optical imaging using biphosphonate fluorescent probes such as Osteosense, through targeting of hydroxyapatite (HA), a biomarker for osteoblastic activity. Additionally, bioluminescence imaging using luciferase expressing tumor lines and micro-CT imaging of the skeleton can enable anatomic characterization of tumor burden and development of bone lesion in bone metastasis models.

Methods: MDA-MB-231-luc-D3H2LN human mammary adenocarcinoma cells (105 cells in 100µl) were injected into the left ventricle of female nu/nu mice on Day 0 approximately 6-7min after IP injection of luciferin (150mg/kg). Bioluminescence scans were used to determine successful injection by distribution of light throughout the body. On Day 14, all tumor pool mice were imaged using bioluminescence and enrolled on study based on incidence of luciferase signals at bone sites. After staging, serial bioluminescence imaging was used to localize tumor signals and determine incidence and growth of bone metastases and micro-CT was used to image the extent of bone lesions associated with the metastases. Additionally, whole body PET scans were used at multiple time points after 90min uptake of 18F-NaF. Images were reconstructed using a 2D OSEM method and localized bone sites segmented and analyzed for standardized uptake value (SUV). Fluorescence imaging was also used 24h after administration of Osteosense 750 to characterize localization of the tracer at the bone sites of interest. After background correction, the bone sites of interest were segmented and analyzed for average efficiency. The 18F-NaF and Osteosense endpoints were correlated with bioluminescence determined tumor burden and location.

Results and Discussion: Both 18F-NaF PET imaging and fluorescent imaging using Osteosense highlighted localized bone signals that could be correlated with bioluminescent signals and micro-CT visualized bone lesions from approximately Day 17. Both the PET and fluorescence imaging approaches showed early indication of bone involvement, presumably through HA, indicating osteoblastic activity. This multi-endpoint approach enabled non-invasive determination of both soft tumor and bone components of metastatic bone disease. An approach like this may enable more quantitative characterization of the early stages of bone metastasis in mouse models, and facilitate development of bone targeted treatments.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4321.