Jin-Bo Yue1, Jia Yang2, Jing Liu3, Jason Lee4, Alvin R Cabrera4, Xin-Dong Sun1, Guang-Hui Bai5, Yu-Hui Li6, Jin-Ming Yu7. 1. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China. 2. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China; Jinan University, Shandong Academy of Medical Sciences, China. 3. Graduate Education Center of Shandong Academy of Medical Sciences, Jinan, China. 4. Department of Radiation Oncology, Duke University Medical Center, Durham, USA. 5. Department of Radiology, The 2nd Affiliated Hospital of Wenzhou Medical University, China. 6. Department of Pathology, Shandong Cancer Hospital and Institute, Jinan, China. 7. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China. Electronic address: sdyujinming@126.com.
Abstract
BACKGROUND AND PURPOSE: FaDu human squamous cell carcinoma (FaDu-hSCC) demonstrates accelerated tumor repopulation during fractionated irradiation with pathological validation (Ki-67 and BrdUrd makers) in a xenograft model system. However, these and other functional assays must be performed ex vivo and post hoc. We propose a novel, in vivo, real-time assay utilizing (18)F-FLT PET. MATERIAL AND METHODS: Nude mice with FaDu-hSCC were irradiated with 12 or 18 fractions of 1.8 Gy ([Dm]=3.0 Gy), either daily or every second day. (18)F-FLT micro-PET scans were performed at different time points, FLT parameters (SUVmax, SUVmean, and T/NT) were measured. Tumor sections were stained for Ki-67 and BrdUrd, a labeling index (LI) was calculated. Imaging-pathology correlation was determined by comparing FLT parameters and immunohistochemical results. RESULTS: Measured SUVmax, SUVmean and T/NT decreased significantly after daily irradiation with 12 fractions in 12 days (P<0.05) and 18 fractions in 18 days (P<0.05). In contrast, these parameters increased in mice treated with 12 fractions in 24 days (P>0.05) and 18 fractions in 36 days (P>0.05), suggesting accelerated repopulation. Similarly, Ki-67 and BrdUrd LIs demonstrated significant decreases with daily irradiation (P<0.05), and increases with every-second-day irradiation (P>0.05). (18)F-FLT parameters correlated strongly with proliferation markers (r(2): 0.679-0.879, P<0.001). CONCLUSIONS: (18)F-FLT parameters were in good agreement with Ki-67 and BrdUrd Li. These results may support a potential role for (18)F-FLT PET in real-time detection of tumor repopulation during fractionated radiotherapy.
BACKGROUND AND PURPOSE: FaDu humansquamous cell carcinoma (FaDu-hSCC) demonstrates accelerated tumor repopulation during fractionated irradiation with pathological validation (Ki-67 and BrdUrd makers) in a xenograft model system. However, these and other functional assays must be performed ex vivo and post hoc. We propose a novel, in vivo, real-time assay utilizing (18)F-FLT PET. MATERIAL AND METHODS:Nude mice with FaDu-hSCC were irradiated with 12 or 18 fractions of 1.8 Gy ([Dm]=3.0 Gy), either daily or every second day. (18)F-FLT micro-PET scans were performed at different time points, FLT parameters (SUVmax, SUVmean, and T/NT) were measured. Tumor sections were stained for Ki-67 and BrdUrd, a labeling index (LI) was calculated. Imaging-pathology correlation was determined by comparing FLT parameters and immunohistochemical results. RESULTS: Measured SUVmax, SUVmean and T/NT decreased significantly after daily irradiation with 12 fractions in 12 days (P<0.05) and 18 fractions in 18 days (P<0.05). In contrast, these parameters increased in mice treated with 12 fractions in 24 days (P>0.05) and 18 fractions in 36 days (P>0.05), suggesting accelerated repopulation. Similarly, Ki-67 and BrdUrd LIs demonstrated significant decreases with daily irradiation (P<0.05), and increases with every-second-day irradiation (P>0.05). (18)F-FLT parameters correlated strongly with proliferation markers (r(2): 0.679-0.879, P<0.001). CONCLUSIONS: (18)F-FLT parameters were in good agreement with Ki-67 and BrdUrd Li. These results may support a potential role for (18)F-FLT PET in real-time detection of tumor repopulation during fractionated radiotherapy.
Authors: Willem Grootjans; Lioe-Fee de Geus-Oei; Esther G C Troost; Eric P Visser; Wim J G Oyen; Johan Bussink Journal: Nat Rev Clin Oncol Date: 2015-04-28 Impact factor: 66.675
Authors: Sonja Schelhaas; Kathrin Heinzmann; Vikram R Bollineni; Gerbrand M Kramer; Yan Liu; John C Waterton; Eric O Aboagye; Anthony F Shields; Dmitry Soloviev; Andreas H Jacobs Journal: Theranostics Date: 2017-01-01 Impact factor: 11.556