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

Jin Bo Yue, Jia Yang, Jing Liu, Jason Lee, Alvin R. Cabrera, Xin Dong Sun, Guang Hui Bai, Yu Hui Li, Jin Ming Yu

Research output: Contribution to journalArticle

10 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)475-481
Number of pages7
JournalRadiotherapy and Oncology
Volume111
Issue number3
DOIs
StatePublished - Jun 2014
Externally publishedYes

Keywords

  • Fractionated radiotherapy
  • Immunohistochemistry
  • Proliferation
  • Tumor repopulation

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