TY - JOUR
T1 - Histopathologic validation of 3′-Deoxy-3′-18F- fluorothymidine PET for detecting tumor repopulation during fractionated radiotherapy of human FaDu squamous cell carcinoma in nude mice
AU - Yue, Jin Bo
AU - Yang, Jia
AU - Liu, Jing
AU - Lee, Jason
AU - Cabrera, Alvin R.
AU - Sun, Xin Dong
AU - Bai, Guang Hui
AU - Li, Yu Hui
AU - Yu, Jin Ming
N1 - Funding Information:
This work was supported by National Nature Science Foundation of China (NSFC) (Project no. 81101700 ). We thank the chief nurse Ningsha Yu for her great assistance and support of the research.
PY - 2014/6
Y1 - 2014/6
N2 - 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 18F-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. 18F-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). 18F-FLT parameters correlated strongly with proliferation markers (r2: 0.679-0.879, P < 0.001). Conclusions 18F-FLT parameters were in good agreement with Ki-67 and BrdUrd Li. These results may support a potential role for 18F-FLT PET in real-time detection of tumor repopulation during fractionated radiotherapy.
AB - 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 18F-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. 18F-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). 18F-FLT parameters correlated strongly with proliferation markers (r2: 0.679-0.879, P < 0.001). Conclusions 18F-FLT parameters were in good agreement with Ki-67 and BrdUrd Li. These results may support a potential role for 18F-FLT PET in real-time detection of tumor repopulation during fractionated radiotherapy.
KW - Fractionated radiotherapy
KW - Immunohistochemistry
KW - Proliferation
KW - Tumor repopulation
UR - https://www.scopus.com/pages/publications/84905223460
U2 - 10.1016/j.radonc.2014.04.002
DO - 10.1016/j.radonc.2014.04.002
M3 - Article
C2 - 24813091
AN - SCOPUS:84905223460
SN - 0167-8140
VL - 111
SP - 475
EP - 481
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
IS - 3
ER -