Evaluating the Accuracy of FUCCI Cell Cycle In Vivo Fluorescent Imaging to Assess Tumor Proliferation in Preclinical Oncology Models.

Autor: Lu Y; Department of Radiology, University of Alabama at Birmingham, Volker Hall G082, 1670 University Boulevard, Birmingham, AL, 35233, USA.; Graduate Biomedical Sciences, University of Alabama at Birmingham, Birmingham, AL, 35233, USA., Massicano AVF; Department of Radiology, University of Alabama at Birmingham, Volker Hall G082, 1670 University Boulevard, Birmingham, AL, 35233, USA., Gallegos CA; Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, 35233, USA., Heinzman KA; Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, 35233, USA., Parish SW; Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, 35233, USA., Warram JM; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.; Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA., Sorace AG; Department of Radiology, University of Alabama at Birmingham, Volker Hall G082, 1670 University Boulevard, Birmingham, AL, 35233, USA. asorace@uabmc.edu.; Graduate Biomedical Sciences, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. asorace@uabmc.edu.; Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. asorace@uabmc.edu.; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. asorace@uabmc.edu.
Jazyk: angličtina
Zdroj: Molecular imaging and biology [Mol Imaging Biol] 2022 Dec; Vol. 24 (6), pp. 898-908. Date of Electronic Publication: 2022 Jun 01.
DOI: 10.1007/s11307-022-01739-9
Abstrakt: 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'-[ 18 F]fluorothymidine ([ 18 F]-FLT) positron emission tomography (PET)/computed tomography (CT) and biological validation through histology. Imaging with [ 18 F]-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, [ 18 F]-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 [ 18 F]-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 [ 18 F]-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.
(© 2022. World Molecular Imaging Society.)
Databáze: MEDLINE
Externí odkaz: