Purpose: The primary goal of this study is to evaluate the accuracy of the fluorescence ubiquitination cell cycle indicator (FUCCI) system with fluorescence in vivo imaging compared to 3'-deoxy-3'-[18F]fluorothymidine ([18F]-FLT) positron emission tomography (PET)/computed tomography (CT) and biological validation through histology. Imaging with [18F]-FLT PET/CT can be used to noninvasively assess cancer cell proliferation and has been utilized in both preclinical and clinical studies. However, a cost-effective and straightforward method for in vivo, cell cycle targeted cancer drug screening is needed prior to moving towards translational imaging methods such as PET/CT.
Procedures: In this study, fluorescent MDA-MB-231-FUCCI tumor growth was monitored weekly with caliper measurements and fluorescent imaging. Seven weeks post-injection, [18F]-FLT PET/CT was performed with a preclinical PET/CT, and tumors samples were harvested for histological analysis.
Results: RFP fluorescent signal significantly correlated with tumor volume (r = 0.8153, p < 0.0001). Cell proliferation measured by GFP fluorescent imaging was correlated with tumor growth rate (r = 0.6497, p < 0.001). Also, GFP+ cells and [18F]-FLT regions of high uptake were both spatially located in the tumor borders, indicating that the FUCCI-IVIS method may provide an accurate assessment of tumor heterogeneity of cell proliferation. The quantification of total GFP signal was correlated with the sum of tumor [18F]-FLT standard uptake value (SUV) (r = 0.5361, p = 0.0724). Finally, histological analysis confirmed viable cells in the tumor and the correlation of GFP + and Ki67 + cells (r = 0.6368, p = 0.0477).
Conclusion: Fluorescent imaging of the cell cycle provides a noninvasive accurate depiction of tumor progression and response to therapy, which may benefit in vivo testing of novel cancer therapeutics that target the cell cycle.
Keywords: Breast cancer; Cell cycle; Drug screening; Molecular imaging; Proliferative cell imaging; TNBC; [18F]-FLT PET/CT.
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