18F-FDG PET biomarkers help detect early metabolic response to irreversible electroporation and predict therapeutic outcomes in a rat liver tumor model

Xifu Wang, Zhanliang Su, Tianchu Lyu, Matteo Figini, Daniele Procissi, Junjie Shangguan, Chong Sun, Bin Wang, Na Shang, Shanzhi Gu, Quanhong Ma, Andrew C. Gordon, Kai Lin, Jian Wang, Robert J Lewandowski, Riad Salem, Vahid Yaghmai, Andrew Christian Larson, Zhuoli Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

Purpose: To test the hypothesis that biomarkers of fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used for the early detection of therapeutic response to irreversible electroporation (IRE) of liver tumor in a rodent liver tumor model. Materials and Methods: The institutional animal care and use committee approved this study. Rats were inoculated with McA-RH7777 liver tumor cells in the left median and left lateral lobes. Tumors were allowed to grow for 7 days to reach a size typically at least 5 mm in longest diameter, as verified with magnetic resonance (MR) imaging. IRE electrodes were inserted, and eight 100-μsec, 2000-V pulses were applied to ablate the tumor tissue in the left median lobe. Tumor in the left lateral lobe served as a control in each animal. PET/computed tomography (CT) and MR imaging measurements were performed at baseline and 3 days after IRE for each animal. Additional MR imaging measurements were obtained 14 days after IRE. After 14-day follow-up MR imaging, rats were euthanized and tumors harvested for hematoxylin-eosin, CD34, and caspase-3 staining. Change in the maximum standardized uptake value (ΔSUVmax) was calculated 3 days after IRE. The maximum lesion diameter change (ΔDmax) was measured 14 days after IRE by using axial T2-weighted imaging. ΔSUVmax and ΔDmax were compared. The apoptosis index was calculated by using caspase-3-stained slices of apoptotic tumor cells. Pearson correlation coefficients were calculated to assess the relationship between ΔSUVmax at 3 days and ΔDmax (or apoptosis index) at 14 days after IRE treatment. Results: ΔSUVmax, ΔDmax, and apoptosis index significantly differed between treated and untreated tumors (P < .001 for all). In treated tumors, there was a strong correlation between ΔSUVmax 3 days after IRE and ΔDmax 14 days after IRE (R = 0.66, P = .01) and between ΔSUVmax 3 days after IRE and apoptosis index 14 days after IRE (R = 0.57, P = .04). Conclusion: 18F-FDG PET imaging biomarkers can be used for the early detection of therapeutic response to IRE treatment of liver tumors in a rodent model.

Original languageEnglish (US)
Pages (from-to)137-145
Number of pages9
JournalRadiology
Volume287
Issue number1
DOIs
StatePublished - Apr 1 2018

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Electroporation
Fluorodeoxyglucose F18
Positron-Emission Tomography
Biomarkers
Liver
Neoplasms
Therapeutics
Magnetic Resonance Imaging
Apoptosis
Caspase 3
Rodentia
Animal Care Committees
Hematoxylin
Eosine Yellowish-(YS)
Electrodes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Wang, Xifu ; Su, Zhanliang ; Lyu, Tianchu ; Figini, Matteo ; Procissi, Daniele ; Shangguan, Junjie ; Sun, Chong ; Wang, Bin ; Shang, Na ; Gu, Shanzhi ; Ma, Quanhong ; Gordon, Andrew C. ; Lin, Kai ; Wang, Jian ; Lewandowski, Robert J ; Salem, Riad ; Yaghmai, Vahid ; Larson, Andrew Christian ; Zhang, Zhuoli. / 18F-FDG PET biomarkers help detect early metabolic response to irreversible electroporation and predict therapeutic outcomes in a rat liver tumor model. In: Radiology. 2018 ; Vol. 287, No. 1. pp. 137-145.
@article{f719d71235c748bb8e361d8b51f91283,
title = "18F-FDG PET biomarkers help detect early metabolic response to irreversible electroporation and predict therapeutic outcomes in a rat liver tumor model",
abstract = "Purpose: To test the hypothesis that biomarkers of fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used for the early detection of therapeutic response to irreversible electroporation (IRE) of liver tumor in a rodent liver tumor model. Materials and Methods: The institutional animal care and use committee approved this study. Rats were inoculated with McA-RH7777 liver tumor cells in the left median and left lateral lobes. Tumors were allowed to grow for 7 days to reach a size typically at least 5 mm in longest diameter, as verified with magnetic resonance (MR) imaging. IRE electrodes were inserted, and eight 100-μsec, 2000-V pulses were applied to ablate the tumor tissue in the left median lobe. Tumor in the left lateral lobe served as a control in each animal. PET/computed tomography (CT) and MR imaging measurements were performed at baseline and 3 days after IRE for each animal. Additional MR imaging measurements were obtained 14 days after IRE. After 14-day follow-up MR imaging, rats were euthanized and tumors harvested for hematoxylin-eosin, CD34, and caspase-3 staining. Change in the maximum standardized uptake value (ΔSUVmax) was calculated 3 days after IRE. The maximum lesion diameter change (ΔDmax) was measured 14 days after IRE by using axial T2-weighted imaging. ΔSUVmax and ΔDmax were compared. The apoptosis index was calculated by using caspase-3-stained slices of apoptotic tumor cells. Pearson correlation coefficients were calculated to assess the relationship between ΔSUVmax at 3 days and ΔDmax (or apoptosis index) at 14 days after IRE treatment. Results: ΔSUVmax, ΔDmax, and apoptosis index significantly differed between treated and untreated tumors (P < .001 for all). In treated tumors, there was a strong correlation between ΔSUVmax 3 days after IRE and ΔDmax 14 days after IRE (R = 0.66, P = .01) and between ΔSUVmax 3 days after IRE and apoptosis index 14 days after IRE (R = 0.57, P = .04). Conclusion: 18F-FDG PET imaging biomarkers can be used for the early detection of therapeutic response to IRE treatment of liver tumors in a rodent model.",
author = "Xifu Wang and Zhanliang Su and Tianchu Lyu and Matteo Figini and Daniele Procissi and Junjie Shangguan and Chong Sun and Bin Wang and Na Shang and Shanzhi Gu and Quanhong Ma and Gordon, {Andrew C.} and Kai Lin and Jian Wang and Lewandowski, {Robert J} and Riad Salem and Vahid Yaghmai and Larson, {Andrew Christian} and Zhuoli Zhang",
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18F-FDG PET biomarkers help detect early metabolic response to irreversible electroporation and predict therapeutic outcomes in a rat liver tumor model. / Wang, Xifu; Su, Zhanliang; Lyu, Tianchu; Figini, Matteo; Procissi, Daniele; Shangguan, Junjie; Sun, Chong; Wang, Bin; Shang, Na; Gu, Shanzhi; Ma, Quanhong; Gordon, Andrew C.; Lin, Kai; Wang, Jian; Lewandowski, Robert J; Salem, Riad; Yaghmai, Vahid; Larson, Andrew Christian; Zhang, Zhuoli.

In: Radiology, Vol. 287, No. 1, 01.04.2018, p. 137-145.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 18F-FDG PET biomarkers help detect early metabolic response to irreversible electroporation and predict therapeutic outcomes in a rat liver tumor model

AU - Wang, Xifu

AU - Su, Zhanliang

AU - Lyu, Tianchu

AU - Figini, Matteo

AU - Procissi, Daniele

AU - Shangguan, Junjie

AU - Sun, Chong

AU - Wang, Bin

AU - Shang, Na

AU - Gu, Shanzhi

AU - Ma, Quanhong

AU - Gordon, Andrew C.

AU - Lin, Kai

AU - Wang, Jian

AU - Lewandowski, Robert J

AU - Salem, Riad

AU - Yaghmai, Vahid

AU - Larson, Andrew Christian

AU - Zhang, Zhuoli

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Purpose: To test the hypothesis that biomarkers of fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used for the early detection of therapeutic response to irreversible electroporation (IRE) of liver tumor in a rodent liver tumor model. Materials and Methods: The institutional animal care and use committee approved this study. Rats were inoculated with McA-RH7777 liver tumor cells in the left median and left lateral lobes. Tumors were allowed to grow for 7 days to reach a size typically at least 5 mm in longest diameter, as verified with magnetic resonance (MR) imaging. IRE electrodes were inserted, and eight 100-μsec, 2000-V pulses were applied to ablate the tumor tissue in the left median lobe. Tumor in the left lateral lobe served as a control in each animal. PET/computed tomography (CT) and MR imaging measurements were performed at baseline and 3 days after IRE for each animal. Additional MR imaging measurements were obtained 14 days after IRE. After 14-day follow-up MR imaging, rats were euthanized and tumors harvested for hematoxylin-eosin, CD34, and caspase-3 staining. Change in the maximum standardized uptake value (ΔSUVmax) was calculated 3 days after IRE. The maximum lesion diameter change (ΔDmax) was measured 14 days after IRE by using axial T2-weighted imaging. ΔSUVmax and ΔDmax were compared. The apoptosis index was calculated by using caspase-3-stained slices of apoptotic tumor cells. Pearson correlation coefficients were calculated to assess the relationship between ΔSUVmax at 3 days and ΔDmax (or apoptosis index) at 14 days after IRE treatment. Results: ΔSUVmax, ΔDmax, and apoptosis index significantly differed between treated and untreated tumors (P < .001 for all). In treated tumors, there was a strong correlation between ΔSUVmax 3 days after IRE and ΔDmax 14 days after IRE (R = 0.66, P = .01) and between ΔSUVmax 3 days after IRE and apoptosis index 14 days after IRE (R = 0.57, P = .04). Conclusion: 18F-FDG PET imaging biomarkers can be used for the early detection of therapeutic response to IRE treatment of liver tumors in a rodent model.

AB - Purpose: To test the hypothesis that biomarkers of fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used for the early detection of therapeutic response to irreversible electroporation (IRE) of liver tumor in a rodent liver tumor model. Materials and Methods: The institutional animal care and use committee approved this study. Rats were inoculated with McA-RH7777 liver tumor cells in the left median and left lateral lobes. Tumors were allowed to grow for 7 days to reach a size typically at least 5 mm in longest diameter, as verified with magnetic resonance (MR) imaging. IRE electrodes were inserted, and eight 100-μsec, 2000-V pulses were applied to ablate the tumor tissue in the left median lobe. Tumor in the left lateral lobe served as a control in each animal. PET/computed tomography (CT) and MR imaging measurements were performed at baseline and 3 days after IRE for each animal. Additional MR imaging measurements were obtained 14 days after IRE. After 14-day follow-up MR imaging, rats were euthanized and tumors harvested for hematoxylin-eosin, CD34, and caspase-3 staining. Change in the maximum standardized uptake value (ΔSUVmax) was calculated 3 days after IRE. The maximum lesion diameter change (ΔDmax) was measured 14 days after IRE by using axial T2-weighted imaging. ΔSUVmax and ΔDmax were compared. The apoptosis index was calculated by using caspase-3-stained slices of apoptotic tumor cells. Pearson correlation coefficients were calculated to assess the relationship between ΔSUVmax at 3 days and ΔDmax (or apoptosis index) at 14 days after IRE treatment. Results: ΔSUVmax, ΔDmax, and apoptosis index significantly differed between treated and untreated tumors (P < .001 for all). In treated tumors, there was a strong correlation between ΔSUVmax 3 days after IRE and ΔDmax 14 days after IRE (R = 0.66, P = .01) and between ΔSUVmax 3 days after IRE and apoptosis index 14 days after IRE (R = 0.57, P = .04). Conclusion: 18F-FDG PET imaging biomarkers can be used for the early detection of therapeutic response to IRE treatment of liver tumors in a rodent model.

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