SU‐GG‐J‐109: Inhomogeneities of Intratumoral FDG Uptake in Human Colon Adenocarcinoma HT29 Tumor Model

Andrei Pugachev, X. Sun, S. Carlin, J. Humm

Research output: Contribution to journalArticle

Abstract

Purpose: It has been shown previously that in rat prostate carcinoma tumor R3327‐AT the highest uptake of 18‐FDG in tumors was observed in the areas of hypoxia rather than the areas of increased blood flow or active cell proliferation. In the present study we investigated the pattern of intratumoral FDG uptake in human colon adenocarcinoma cell line HT29. Method and Materials: Three nude rats were inoculated with HT29 cells. When the tumors reached 25mm in diameter, the animals were injected with 18‐FDG, pimonidazole, and bromodeoxyuridine (BrdU). 1hr later injection animals were injected with Hoechst33342 and sacrificed. Tumors were immediately dissected, frozen and sectioned. One section from each tumor was placed onto a phosphor plate for autoradiography. The images of the fluorescence produced by Hoechst33342 and by fluorescent antibodies raised against pimonidazole and BrdU were acquired from the adjacent sections and co‐registered. Results: All tumors in the study had extensive necrosis well intermixed with viable tumor tissue. Typically, hypoxia was forming bands about 100μm wide at the interface between viable tissue and necrosis. Analysis of the autoradiography data demonstrated associations between 18F‐FDG uptake and all of the markers studied. However, when analysis is done on the viable tumor tissue only by carefully masking out the necrotic areas, 0FDG uptake was positively correlated with staining intensity of pimonidazole and negatively correlated with Hoechst and BrdU. Conclusion: In larger tumors with complicated morphology it is necrotic fraction that plays crucial role in forming FDG uptake variations rather than any of the microenvironmental parameters considered. However, in the viable tumor tissue FDG uptake was positively correlated with staining intensity of pimonidazole and negatively correlated with Hoechst and BrdU, thus demonstrating association of increased FDG uptake with hypoxia.

Original languageEnglish (US)
Number of pages1
JournalMedical Physics
Volume35
Issue number6
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

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Colon
Adenocarcinoma
Bromodeoxyuridine
Neoplasms
Fluorodeoxyglucose F18
Autoradiography
Necrosis
Nude Rats
Staining and Labeling
HT29 Cells
Prostate
Fluorescence
Cell Proliferation
Carcinoma
Cell Line
Injections
pimonidazole
Antibodies
Hypoxia

ASJC Scopus subject areas

  • Biophysics
  • Radiology Nuclear Medicine and imaging

Cite this

SU‐GG‐J‐109 : Inhomogeneities of Intratumoral FDG Uptake in Human Colon Adenocarcinoma HT29 Tumor Model. / Pugachev, Andrei; Sun, X.; Carlin, S.; Humm, J.

In: Medical Physics, Vol. 35, No. 6, 01.01.2008.

Research output: Contribution to journalArticle

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abstract = "Purpose: It has been shown previously that in rat prostate carcinoma tumor R3327‐AT the highest uptake of 18‐FDG in tumors was observed in the areas of hypoxia rather than the areas of increased blood flow or active cell proliferation. In the present study we investigated the pattern of intratumoral FDG uptake in human colon adenocarcinoma cell line HT29. Method and Materials: Three nude rats were inoculated with HT29 cells. When the tumors reached 25mm in diameter, the animals were injected with 18‐FDG, pimonidazole, and bromodeoxyuridine (BrdU). 1hr later injection animals were injected with Hoechst33342 and sacrificed. Tumors were immediately dissected, frozen and sectioned. One section from each tumor was placed onto a phosphor plate for autoradiography. The images of the fluorescence produced by Hoechst33342 and by fluorescent antibodies raised against pimonidazole and BrdU were acquired from the adjacent sections and co‐registered. Results: All tumors in the study had extensive necrosis well intermixed with viable tumor tissue. Typically, hypoxia was forming bands about 100μm wide at the interface between viable tissue and necrosis. Analysis of the autoradiography data demonstrated associations between 18F‐FDG uptake and all of the markers studied. However, when analysis is done on the viable tumor tissue only by carefully masking out the necrotic areas, 0FDG uptake was positively correlated with staining intensity of pimonidazole and negatively correlated with Hoechst and BrdU. Conclusion: In larger tumors with complicated morphology it is necrotic fraction that plays crucial role in forming FDG uptake variations rather than any of the microenvironmental parameters considered. However, in the viable tumor tissue FDG uptake was positively correlated with staining intensity of pimonidazole and negatively correlated with Hoechst and BrdU, thus demonstrating association of increased FDG uptake with hypoxia.",
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