Tumour microenvironment heterogeneity affects the perceived spatial concordance between the intratumoural patterns of cell proliferation and 18F-fluorothymidine uptake

Marian Axente, Jun He, Christopher P. Bass, Jerry I. Hirsch, Gobalakrishnan Sundaresan, Jeffrey Williamson, Jamal Zweit, Andrei Pugachev

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background and purpose: PET imaging with 18F-fluorothymidine (18F-FLT) can potentially be used to identify tumour subvolumes for selective dose escalation in radiation therapy. The purpose of this study is to analyse the co-localization of intratumoural patterns of cell proliferation with 18F-FLT tracer uptake. Materials and methods: Mice bearing FaDu or SQ20B xenograft tumours were injected with 18F-FLT, and bromodeoxyuridine (proliferation marker). Ex vivo images of the spatial pattern of intratumoural 18F-FLT uptake and that of bromodeoxyuridine DNA incorporation were obtained from thin tumour tissue sections. These images were segmented by thresholding and Relative Operating Characteristic (ROC) curves and Dice similarity indices were evaluated. Results: The thresholds at which maximum overlap occurred between FLT-segmented areas and areas of active cell proliferation were significantly different for the two xenograft tumour models, whereas the median Dice values were not. However, ROC analysis indicated that segmented FLT images were more specific at detecting the proliferation pattern in FaDu tumours than in SQ20B tumours. Conclusion: Highly dispersed patterns of cell proliferation observed in certain tumours can affect the perceived spatial concordance between the spatial pattern of 18F-FLT uptake and that of cell proliferation even when high-resolution ex vivo autoradiography imaging is used for 18F-FLT imaging.

Original languageEnglish (US)
Pages (from-to)49-56
Number of pages8
JournalRadiotherapy and Oncology
Volume105
Issue number1
DOIs
StatePublished - Oct 1 2012
Externally publishedYes

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Tumor Microenvironment
Cell Proliferation
Neoplasms
Bromodeoxyuridine
Heterografts
Autoradiography
Radiotherapy
DNA

Keywords

  • Autoradiography
  • FLT
  • FLT PET
  • Fluorothymidine
  • Image-guided radiotherapy
  • Selective boost
  • Small animal tumour model
  • Tumour cell proliferation

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Tumour microenvironment heterogeneity affects the perceived spatial concordance between the intratumoural patterns of cell proliferation and 18F-fluorothymidine uptake. / Axente, Marian; He, Jun; Bass, Christopher P.; Hirsch, Jerry I.; Sundaresan, Gobalakrishnan; Williamson, Jeffrey; Zweit, Jamal; Pugachev, Andrei.

In: Radiotherapy and Oncology, Vol. 105, No. 1, 01.10.2012, p. 49-56.

Research output: Contribution to journalArticle

Axente, Marian ; He, Jun ; Bass, Christopher P. ; Hirsch, Jerry I. ; Sundaresan, Gobalakrishnan ; Williamson, Jeffrey ; Zweit, Jamal ; Pugachev, Andrei. / Tumour microenvironment heterogeneity affects the perceived spatial concordance between the intratumoural patterns of cell proliferation and 18F-fluorothymidine uptake. In: Radiotherapy and Oncology. 2012 ; Vol. 105, No. 1. pp. 49-56.
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abstract = "Background and purpose: PET imaging with 18F-fluorothymidine (18F-FLT) can potentially be used to identify tumour subvolumes for selective dose escalation in radiation therapy. The purpose of this study is to analyse the co-localization of intratumoural patterns of cell proliferation with 18F-FLT tracer uptake. Materials and methods: Mice bearing FaDu or SQ20B xenograft tumours were injected with 18F-FLT, and bromodeoxyuridine (proliferation marker). Ex vivo images of the spatial pattern of intratumoural 18F-FLT uptake and that of bromodeoxyuridine DNA incorporation were obtained from thin tumour tissue sections. These images were segmented by thresholding and Relative Operating Characteristic (ROC) curves and Dice similarity indices were evaluated. Results: The thresholds at which maximum overlap occurred between FLT-segmented areas and areas of active cell proliferation were significantly different for the two xenograft tumour models, whereas the median Dice values were not. However, ROC analysis indicated that segmented FLT images were more specific at detecting the proliferation pattern in FaDu tumours than in SQ20B tumours. Conclusion: Highly dispersed patterns of cell proliferation observed in certain tumours can affect the perceived spatial concordance between the spatial pattern of 18F-FLT uptake and that of cell proliferation even when high-resolution ex vivo autoradiography imaging is used for 18F-FLT imaging.",
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AU - Sundaresan, Gobalakrishnan

AU - Williamson, Jeffrey

AU - Zweit, Jamal

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N2 - Background and purpose: PET imaging with 18F-fluorothymidine (18F-FLT) can potentially be used to identify tumour subvolumes for selective dose escalation in radiation therapy. The purpose of this study is to analyse the co-localization of intratumoural patterns of cell proliferation with 18F-FLT tracer uptake. Materials and methods: Mice bearing FaDu or SQ20B xenograft tumours were injected with 18F-FLT, and bromodeoxyuridine (proliferation marker). Ex vivo images of the spatial pattern of intratumoural 18F-FLT uptake and that of bromodeoxyuridine DNA incorporation were obtained from thin tumour tissue sections. These images were segmented by thresholding and Relative Operating Characteristic (ROC) curves and Dice similarity indices were evaluated. Results: The thresholds at which maximum overlap occurred between FLT-segmented areas and areas of active cell proliferation were significantly different for the two xenograft tumour models, whereas the median Dice values were not. However, ROC analysis indicated that segmented FLT images were more specific at detecting the proliferation pattern in FaDu tumours than in SQ20B tumours. Conclusion: Highly dispersed patterns of cell proliferation observed in certain tumours can affect the perceived spatial concordance between the spatial pattern of 18F-FLT uptake and that of cell proliferation even when high-resolution ex vivo autoradiography imaging is used for 18F-FLT imaging.

AB - Background and purpose: PET imaging with 18F-fluorothymidine (18F-FLT) can potentially be used to identify tumour subvolumes for selective dose escalation in radiation therapy. The purpose of this study is to analyse the co-localization of intratumoural patterns of cell proliferation with 18F-FLT tracer uptake. Materials and methods: Mice bearing FaDu or SQ20B xenograft tumours were injected with 18F-FLT, and bromodeoxyuridine (proliferation marker). Ex vivo images of the spatial pattern of intratumoural 18F-FLT uptake and that of bromodeoxyuridine DNA incorporation were obtained from thin tumour tissue sections. These images were segmented by thresholding and Relative Operating Characteristic (ROC) curves and Dice similarity indices were evaluated. Results: The thresholds at which maximum overlap occurred between FLT-segmented areas and areas of active cell proliferation were significantly different for the two xenograft tumour models, whereas the median Dice values were not. However, ROC analysis indicated that segmented FLT images were more specific at detecting the proliferation pattern in FaDu tumours than in SQ20B tumours. Conclusion: Highly dispersed patterns of cell proliferation observed in certain tumours can affect the perceived spatial concordance between the spatial pattern of 18F-FLT uptake and that of cell proliferation even when high-resolution ex vivo autoradiography imaging is used for 18F-FLT imaging.

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