Abstract LB-510: Longitudinal imaging of melanoma cancer cell metastasis in a preclinical model by bioluminescence, PET/CT, and MRI

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Metastasis of cancer cells from the primary tumor are a leading cause of poor prognosis and death from cancer. The lung is the most common organ for metastatic spread of cancer and leads to 20-50% of cancer-related deaths. Early detection of cancer metastasis to the lung and other organs could be beneficial in disease management. In animal studies, most secondary-site disseminated tumors are evaluated by optical imaging, and gross examination at necropsy and subsequent histopathological analysis. These techniques are limited in that they do not offer the ability to monitor animals during the course of tumor development, and optical microscopy may have inadequate field of view (3-D morphometrics) for thorough tumor evaluation. Noninvasive imaging allows for serial imaging of the same animal, with the ability to repeat measurements in real-time to enhance the observation of disease progression and therapeutic response. Here, we compared the multimodal noninvasive whole-body imaging techniques bioluminescence, 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography (PET)/ computed tomography (CT), and magnetic resonance imaging (MRI) to image lung metastasis development following intravenous injection of melanoma cells (B16-F10 melanoma cell line expressing luciferase gene) in C57BL/6. By bioluminescence imaging, tumor cell localization in the lungs was evident as early as 3 days (1 x 105 photons/sec; total flux) post cancer cell inoculation and steadily increased through the end of week four (1 x 108 photons/sec; total flux). The increase in the lung tumor burden was confirmed by lung histopathology. As it was difficult to de-convolve the effects of photon flux spreading from lungs over other organs, other metastatic sites were not evaluated by bioluminescence. CT and 18F-FDG-PET are used clinically to image lung metastasis and offer excellent resolution of anatomical and metabolic details of cancer cells. We were able to image metastatic nodules in the lung by PET/CT at week four, which showed a strong correlation with histopathology analysis. [18F]FDG-PET/CT also revealed metastasis in the kidney and mesentery and were confirmed by histopathology. T2-weighted MRI at week 4 identified several lung tumors and metastatic cancers in the abdomen. A comparison of [18F]FDG/PET at week 4 to MRI and CT displayed several highly metabolic regions within the tumors. Histopathology confirmed the metastatic spread of the melanoma cells to the lung, mediastinum, kidney, and mesentery. Funded by NCI contract No. HHSN261200800001E. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-510. doi:1538-7445.AM2012-LB-510