Yun Lu1,2, Adriana V F Massicano1, Carlos A Gallegos3, Katherine A Heinzman3, Sean W Parish3, Jason M Warram4,5, Anna G Sorace6,7,8,9. 1. Department of Radiology, University of Alabama at Birmingham, Volker Hall G082, 1670 University Boulevard, Birmingham, AL, 35233, USA. 2. Graduate Biomedical Sciences, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. 3. Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. 4. O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. 5. Department of Otolaryngology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. 6. Department of Radiology, University of Alabama at Birmingham, Volker Hall G082, 1670 University Boulevard, Birmingham, AL, 35233, USA. asorace@uabmc.edu. 7. Graduate Biomedical Sciences, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. asorace@uabmc.edu. 8. Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. asorace@uabmc.edu. 9. O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, 35233, USA. asorace@uabmc.edu.
Abstract
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.
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.
Authors: Peter Schmid; Jacinta Abraham; Stephen Chan; Duncan Wheatley; Adrian Murray Brunt; Gia Nemsadze; Richard D Baird; Yeon Hee Park; Peter S Hall; Timothy Perren; Robert C Stein; László Mangel; Jean-Marc Ferrero; Melissa Phillips; John Conibear; Javier Cortes; Andrew Foxley; Elza C de Bruin; Robert McEwen; Daniel Stetson; Brian Dougherty; Shah-Jalal Sarker; Aaron Prendergast; Max McLaughlin-Callan; Matthew Burgess; Cheryl Lawrence; Hayley Cartwright; Kelly Mousa; Nicholas C Turner Journal: J Clin Oncol Date: 2019-12-16 Impact factor: 44.544
Authors: Azadeh Elmi; Mehran Makvandi; Chi-Chang Weng; Catherine Hou; Amy S Clark; Robert H Mach; David A Mankoff Journal: Clin Cancer Res Date: 2019-01-28 Impact factor: 13.801
Authors: H P Eikesdal; S Yndestad; A Elzawahry; A Llop-Guevara; B Gilje; E S Blix; H Espelid; S Lundgren; J Geisler; G Vagstad; A Venizelos; L Minsaas; B Leirvaag; E G Gudlaugsson; O K Vintermyr; H S Aase; T Aas; J Balmaña; V Serra; E A M Janssen; S Knappskog; P E Lønning Journal: Ann Oncol Date: 2020-11-24 Impact factor: 32.976