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18F-EF5 PET Is Predictive of Response to Fractionated Radiotherapy in Preclinical Tumor Models.

Ali R, Apte S, Vilalta M, Subbarayan M, Miao Z, Chin FT, Graves EE - PLoS ONE (2015)

Bottom Line: We evaluated the relationship between pre-treatment positron emission tomography (PET) using the hypoxic tracer 18F-[2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3- pentafluoropropyl) acetamide] (18F-EF5) and the response of preclinical tumor models to a range of fractionated radiotherapies.Based on these results, 80 A549 tumors were subsequently grown and imaged using 18F-EF5 PET, and then treated with one, two, or four fraction radiation treatments to a total dose of 10-40 Gy.Terminal histologic analysis was performed to validate 18F-EF5 PET measures of hypoxia.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Stanford University, Stanford, CA, United States of America.

ABSTRACT
We evaluated the relationship between pre-treatment positron emission tomography (PET) using the hypoxic tracer 18F-[2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3- pentafluoropropyl) acetamide] (18F-EF5) and the response of preclinical tumor models to a range of fractionated radiotherapies. Subcutaneous HT29, A549 and RKO tumors grown in nude mice were imaged using 18F-EF5 positron emission tomography (PET) in order to characterize the extent and heterogeneity of hypoxia in these systems. Based on these results, 80 A549 tumors were subsequently grown and imaged using 18F-EF5 PET, and then treated with one, two, or four fraction radiation treatments to a total dose of 10-40 Gy. Response was monitored by serial caliper measurements of tumor volume. Longitudinal post-treatment 18F-EF5 PET imaging was performed on a subset of tumors. Terminal histologic analysis was performed to validate 18F-EF5 PET measures of hypoxia. EF5-positive tumors responded more poorly to low dose single fraction irradiation relative to EF5-negative tumors, however both groups responded similarly to larger single fraction doses. Irradiated tumors exhibited reduced 18F-EF5 uptake one month after treatment compared to control tumors. These findings indicate that pre- treatment 18F-EF5 PET can predict the response of tumors to single fraction radiation treatment. However, increasing the number of fractions delivered abrogates the difference in response between tumors with high and low EF5 uptake pre-treatment, in agreement with traditional radiobiology.

No MeSH data available.


Related in: MedlinePlus

Effect of radiation on tumor 18F-EF5 uptake.(A) Representative axial 18F-EF5 PET images of two tumors at 1 day pre-treatment and 13 / 32 days post-treatment. Solid arrow denotes unirradiated control tumor, and dashed arrow denotes tumor which was treated with 20 Gy. (B,C) Plots showing changes in 18F-EF5 uptake and volume, respectively, in control (n = 6) and irradiated (n = 6) tumors during the treatment timecourse.
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pone.0139425.g004: Effect of radiation on tumor 18F-EF5 uptake.(A) Representative axial 18F-EF5 PET images of two tumors at 1 day pre-treatment and 13 / 32 days post-treatment. Solid arrow denotes unirradiated control tumor, and dashed arrow denotes tumor which was treated with 20 Gy. (B,C) Plots showing changes in 18F-EF5 uptake and volume, respectively, in control (n = 6) and irradiated (n = 6) tumors during the treatment timecourse.

Mentions: Fig 4A shows the changes in tumor hypoxia post-irradiation as revealed by 18F-EF5 microPET imaging. The control tumor increased in volume and 18F-EF5 uptake over the course of a month, whereas the irradiated tumor shows a smaller increase in size and 18F- EF5 uptake. Fig 4B compares the T/MPET values for the control and irradiated tumors at each time point. Prior to treatment, there is no difference between the two groups. After 13 days, there is a reduction in the T/MPET of the irradiated group that is not statistically significant. After 32 days, there is a noticeable decrease in the T/MPET for both groups, and the irradiated tumor T/MPET is significantly lower than that of the control group (p = 0.03). Fig 4C shows an increase in tumor volume for control tumors, while the irradiated tumor volume remains constant over 32 days. H&E sections of tumors after 32 days reveal large regions of necrosis in control tumors, and smaller necrotic regions accompanied by macroscopic blood pools in treated tumors (S4 Fig).


18F-EF5 PET Is Predictive of Response to Fractionated Radiotherapy in Preclinical Tumor Models.

Ali R, Apte S, Vilalta M, Subbarayan M, Miao Z, Chin FT, Graves EE - PLoS ONE (2015)

Effect of radiation on tumor 18F-EF5 uptake.(A) Representative axial 18F-EF5 PET images of two tumors at 1 day pre-treatment and 13 / 32 days post-treatment. Solid arrow denotes unirradiated control tumor, and dashed arrow denotes tumor which was treated with 20 Gy. (B,C) Plots showing changes in 18F-EF5 uptake and volume, respectively, in control (n = 6) and irradiated (n = 6) tumors during the treatment timecourse.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4592127&req=5

pone.0139425.g004: Effect of radiation on tumor 18F-EF5 uptake.(A) Representative axial 18F-EF5 PET images of two tumors at 1 day pre-treatment and 13 / 32 days post-treatment. Solid arrow denotes unirradiated control tumor, and dashed arrow denotes tumor which was treated with 20 Gy. (B,C) Plots showing changes in 18F-EF5 uptake and volume, respectively, in control (n = 6) and irradiated (n = 6) tumors during the treatment timecourse.
Mentions: Fig 4A shows the changes in tumor hypoxia post-irradiation as revealed by 18F-EF5 microPET imaging. The control tumor increased in volume and 18F-EF5 uptake over the course of a month, whereas the irradiated tumor shows a smaller increase in size and 18F- EF5 uptake. Fig 4B compares the T/MPET values for the control and irradiated tumors at each time point. Prior to treatment, there is no difference between the two groups. After 13 days, there is a reduction in the T/MPET of the irradiated group that is not statistically significant. After 32 days, there is a noticeable decrease in the T/MPET for both groups, and the irradiated tumor T/MPET is significantly lower than that of the control group (p = 0.03). Fig 4C shows an increase in tumor volume for control tumors, while the irradiated tumor volume remains constant over 32 days. H&E sections of tumors after 32 days reveal large regions of necrosis in control tumors, and smaller necrotic regions accompanied by macroscopic blood pools in treated tumors (S4 Fig).

Bottom Line: We evaluated the relationship between pre-treatment positron emission tomography (PET) using the hypoxic tracer 18F-[2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3- pentafluoropropyl) acetamide] (18F-EF5) and the response of preclinical tumor models to a range of fractionated radiotherapies.Based on these results, 80 A549 tumors were subsequently grown and imaged using 18F-EF5 PET, and then treated with one, two, or four fraction radiation treatments to a total dose of 10-40 Gy.Terminal histologic analysis was performed to validate 18F-EF5 PET measures of hypoxia.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Oncology, Stanford University, Stanford, CA, United States of America.

ABSTRACT
We evaluated the relationship between pre-treatment positron emission tomography (PET) using the hypoxic tracer 18F-[2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3- pentafluoropropyl) acetamide] (18F-EF5) and the response of preclinical tumor models to a range of fractionated radiotherapies. Subcutaneous HT29, A549 and RKO tumors grown in nude mice were imaged using 18F-EF5 positron emission tomography (PET) in order to characterize the extent and heterogeneity of hypoxia in these systems. Based on these results, 80 A549 tumors were subsequently grown and imaged using 18F-EF5 PET, and then treated with one, two, or four fraction radiation treatments to a total dose of 10-40 Gy. Response was monitored by serial caliper measurements of tumor volume. Longitudinal post-treatment 18F-EF5 PET imaging was performed on a subset of tumors. Terminal histologic analysis was performed to validate 18F-EF5 PET measures of hypoxia. EF5-positive tumors responded more poorly to low dose single fraction irradiation relative to EF5-negative tumors, however both groups responded similarly to larger single fraction doses. Irradiated tumors exhibited reduced 18F-EF5 uptake one month after treatment compared to control tumors. These findings indicate that pre- treatment 18F-EF5 PET can predict the response of tumors to single fraction radiation treatment. However, increasing the number of fractions delivered abrogates the difference in response between tumors with high and low EF5 uptake pre-treatment, in agreement with traditional radiobiology.

No MeSH data available.


Related in: MedlinePlus