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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 8/2019

24.05.2019 | Original Article

Diffusion-weighted MRI and 18F-FDG PET correlation with immunity in early radiotherapy response in BNL hepatocellular carcinoma mouse model: timeline validation

verfasst von: Yi-Hsiu Chung, Ching-Fang Yu, Shao-Chieh Chiu, Han Chiu, Shin-Ting Hsu, Ching-Rong Wu, Chung-Lin Yang, Ji-Hong Hong, Tzu-Chen Yen, Fang-Hsin Chen

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 8/2019

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Abstract

Purpose

Imaging probes/biomarkers that are correlated with molecular or microenvironmental alterations in tumors have been used not only in diagnosing cancer but also in assessing the efficacy of cancer treatment. We evaluated the early response of hepatocellular carcinoma (HCC) to radiation treatment using T2-weighted magnetic resonance imaging (MRI), diffusion-weighted (DW) MRI, and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET).

Methods

Orthotopic HCC tumors were established in the right liver lobe of Balb/c mice. Mice were longitudinally scanned using T2-weighted/DW MRI and 18F-FDG PET 1 day before and on days 1, 3, 6, 9 and 13 after irradiation with 15 Gy to the right liver lobe to determine tumor size, apparent diffusion coefficient (ADC) value, and maximum standardized uptake value. Immunohistochemical (IHC) staining was performed to validate the tumor microenvironment.

Results

Irradiation markedly retarded tumor growth in the orthotopic HCC model and led to increaes in ADC values as early as on day 1 after irradiation. Irradiation also resulted in increases in 18F-FDG uptake on day 1 that were sustained until the end of the observation period. IHC staining revealed a decrease in the number of proliferative cells and a continuous macrophage influx into irradiated tumors, which dramatically altered the tumor microenvironment. Lastly, in vitro coculture of HCC cells and macrophages led to interaction between the cells and enhanced the cellular uptake of 18F-FDG.

Conclusion

ADC values and 18F-FDG uptake measured using DW MRI and 18F-FDG PET serve as potential biomarkers for early assessment of HCC tumor responses to radiation therapy.
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Literatur
1.
Zurück zum Zitat Ippolito D, Fior D, Trattenero C, Ponti ED, Drago S, Guerra L, et al. Combined value of apparent diffusion coefficient-standardized uptake value max in evaluation of post-treated locally advanced rectal cancer. World J Radiol. 2015;7:509–20. CrossRefPubMedPubMedCentral Ippolito D, Fior D, Trattenero C, Ponti ED, Drago S, Guerra L, et al. Combined value of apparent diffusion coefficient-standardized uptake value max in evaluation of post-treated locally advanced rectal cancer. World J Radiol. 2015;7:509–20. CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Reed GB Jr, Cox AJ Jr. The human liver after radiation injury. A form of veno-occlusive disease. Am J Pathol. 1966;48:597–611. PubMedPubMedCentral Reed GB Jr, Cox AJ Jr. The human liver after radiation injury. A form of veno-occlusive disease. Am J Pathol. 1966;48:597–611. PubMedPubMedCentral
4.
Zurück zum Zitat Kalogeridi MA, Zygogianni A, Kyrgias G, Kouvaris J, Chatziioannou S, Kelekis N, et al. Role of radiotherapy in the management of hepatocellular carcinoma: a systematic review. World J Hepatol. 2015;7:101–12. CrossRefPubMedPubMedCentral Kalogeridi MA, Zygogianni A, Kyrgias G, Kouvaris J, Chatziioannou S, Kelekis N, et al. Role of radiotherapy in the management of hepatocellular carcinoma: a systematic review. World J Hepatol. 2015;7:101–12. CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16. CrossRefPubMed Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16. CrossRefPubMed
6.
Zurück zum Zitat Oya N, Nagata Y, Tamaki N, Takagi T, Murata R, Magata Y, et al. FDG-PET evaluation of therapeutic effects on VX2 liver tumor. J Nucl Med. 1996;37:296–302. PubMed Oya N, Nagata Y, Tamaki N, Takagi T, Murata R, Magata Y, et al. FDG-PET evaluation of therapeutic effects on VX2 liver tumor. J Nucl Med. 1996;37:296–302. PubMed
7.
Zurück zum Zitat Santos P, Peck KK, Arevalo-Perez J, Karimi S, Lis E, Yamada Y, et al. T1-weighted dynamic contrast-enhanced MR perfusion imaging characterizes tumor response to radiation therapy in chordoma. AJNR Am J Neuroradiol. 2017;38:2210–6. CrossRefPubMedPubMedCentral Santos P, Peck KK, Arevalo-Perez J, Karimi S, Lis E, Yamada Y, et al. T1-weighted dynamic contrast-enhanced MR perfusion imaging characterizes tumor response to radiation therapy in chordoma. AJNR Am J Neuroradiol. 2017;38:2210–6. CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Magne N, Toillon RA, Bottero V, Didelot C, Houtte PV, Gerard JP, et al. NF-kappaB modulation and ionizing radiation: mechanisms and future directions for cancer treatment. Cancer Lett. 2006;231:158–68. CrossRefPubMed Magne N, Toillon RA, Bottero V, Didelot C, Houtte PV, Gerard JP, et al. NF-kappaB modulation and ionizing radiation: mechanisms and future directions for cancer treatment. Cancer Lett. 2006;231:158–68. CrossRefPubMed
9.
Zurück zum Zitat Nair VS, Gevaert O, Davidzon G, Plevritis SK, West R. NF-kappaB protein expression associates with (18)F-FDG PET tumor uptake in non-small cell lung cancer: a radiogenomics validation study to understand tumor metabolism. Lung Cancer. 2014;83:189–96. CrossRefPubMed Nair VS, Gevaert O, Davidzon G, Plevritis SK, West R. NF-kappaB protein expression associates with (18)F-FDG PET tumor uptake in non-small cell lung cancer: a radiogenomics validation study to understand tumor metabolism. Lung Cancer. 2014;83:189–96. CrossRefPubMed
10.
Zurück zum Zitat Purandare NC, Puranik AD, Shah S, Agrawal A, Rangarajan V. Post-treatment appearances, pitfalls, and patterns of failure in head and neck cancer on FDG PET/CT imaging. Indian J Nucl Med. 2014;29:151–7. CrossRefPubMedPubMedCentral Purandare NC, Puranik AD, Shah S, Agrawal A, Rangarajan V. Post-treatment appearances, pitfalls, and patterns of failure in head and neck cancer on FDG PET/CT imaging. Indian J Nucl Med. 2014;29:151–7. CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Sanuki N, Takeda A, Oku Y, Eriguchi T, Nishimura S, Aoki Y, et al. Threshold doses for focal liver reaction after stereotactic ablative body radiation therapy for small hepatocellular carcinoma depend on liver function: evaluation on magnetic resonance imaging with Gd-EOB-DTPA. Int J Radiat Oncol Biol Phys. 2014;88:306–11. CrossRefPubMed Sanuki N, Takeda A, Oku Y, Eriguchi T, Nishimura S, Aoki Y, et al. Threshold doses for focal liver reaction after stereotactic ablative body radiation therapy for small hepatocellular carcinoma depend on liver function: evaluation on magnetic resonance imaging with Gd-EOB-DTPA. Int J Radiat Oncol Biol Phys. 2014;88:306–11. CrossRefPubMed
12.
Zurück zum Zitat Liu HL, Hsu PH, Lin CY, Huang CW, Chai WY, Chu PC, et al. Focused ultrasound enhances central nervous system delivery of bevacizumab for malignant glioma treatment. Radiology. 2016;281:99–108. CrossRefPubMed Liu HL, Hsu PH, Lin CY, Huang CW, Chai WY, Chu PC, et al. Focused ultrasound enhances central nervous system delivery of bevacizumab for malignant glioma treatment. Radiology. 2016;281:99–108. CrossRefPubMed
13.
Zurück zum Zitat Chen L, Liu M, Bao J, Xia Y, Zhang J, Zhang L, et al. The correlation between apparent diffusion coefficient and tumor cellularity in patients: a meta-analysis. PLoS One. 2013;8:e79008. CrossRefPubMedPubMedCentral Chen L, Liu M, Bao J, Xia Y, Zhang J, Zhang L, et al. The correlation between apparent diffusion coefficient and tumor cellularity in patients: a meta-analysis. PLoS One. 2013;8:e79008. CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Shih YH, Peng CL, Chiang PF, Lin WJ, Luo TY, Shieh MJ. Therapeutic and scintigraphic applications of polymeric micelles: combination of chemotherapy and radiotherapy in hepatocellular carcinoma. Int J Nanomedicine. 2015;10:7443–54. CrossRefPubMedPubMedCentral Shih YH, Peng CL, Chiang PF, Lin WJ, Luo TY, Shieh MJ. Therapeutic and scintigraphic applications of polymeric micelles: combination of chemotherapy and radiotherapy in hepatocellular carcinoma. Int J Nanomedicine. 2015;10:7443–54. CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Chen FH, Wang CC, Liu HL, Fu SY, Yu CF, Chang C, et al. Decline of tumor vascular function as assessed by dynamic contrast-enhanced magnetic resonance imaging is associated with poor responses to radiation therapy and chemotherapy. Int J Radiat Oncol Biol Phys. 2016;95:1495–503. CrossRefPubMed Chen FH, Wang CC, Liu HL, Fu SY, Yu CF, Chang C, et al. Decline of tumor vascular function as assessed by dynamic contrast-enhanced magnetic resonance imaging is associated with poor responses to radiation therapy and chemotherapy. Int J Radiat Oncol Biol Phys. 2016;95:1495–503. CrossRefPubMed
16.
Zurück zum Zitat Galons JP, Lope-Piedrafita S, Divijak JL, Corum C, Gillies RJ, Trouard TP. Uncovering of intracellular water in cultured cells. Magn Reson Med. 2005;54:79–86. CrossRefPubMed Galons JP, Lope-Piedrafita S, Divijak JL, Corum C, Gillies RJ, Trouard TP. Uncovering of intracellular water in cultured cells. Magn Reson Med. 2005;54:79–86. CrossRefPubMed
17.
Zurück zum Zitat Harkins KD, Galons JP, Secomb TW, Trouard TP. Assessment of the effects of cellular tissue properties on ADC measurements by numerical simulation of water diffusion. Magn Reson Med. 2009;62:1414–22. CrossRefPubMedPubMedCentral Harkins KD, Galons JP, Secomb TW, Trouard TP. Assessment of the effects of cellular tissue properties on ADC measurements by numerical simulation of water diffusion. Magn Reson Med. 2009;62:1414–22. CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Surov A, Meyer HJ, Wienke A. Correlation between apparent diffusion coefficient (ADC) and cellularity is different in several tumors: a meta-analysis. Oncotarget. 2017;8:59492–9. PubMedPubMedCentral Surov A, Meyer HJ, Wienke A. Correlation between apparent diffusion coefficient (ADC) and cellularity is different in several tumors: a meta-analysis. Oncotarget. 2017;8:59492–9. PubMedPubMedCentral
19.
Zurück zum Zitat Yoshikawa MI, Ohsumi S, Sugata S, Kataoka M, Takashima S, Mochizuki T, et al. Relation between cancer cellularity and apparent diffusion coefficient values using diffusion-weighted magnetic resonance imaging in breast cancer. Radiat Med. 2008;26:222–6. CrossRefPubMed Yoshikawa MI, Ohsumi S, Sugata S, Kataoka M, Takashima S, Mochizuki T, et al. Relation between cancer cellularity and apparent diffusion coefficient values using diffusion-weighted magnetic resonance imaging in breast cancer. Radiat Med. 2008;26:222–6. CrossRefPubMed
20.
Zurück zum Zitat Zhao YL, Guo QQ, Yang GR, Wang QD. Early changes in apparent diffusion coefficient as an indicator of response to sorafenib in hepatocellular carcinoma. J Zhejiang Univ Sci B. 2014;15:713–9. CrossRefPubMedPubMedCentral Zhao YL, Guo QQ, Yang GR, Wang QD. Early changes in apparent diffusion coefficient as an indicator of response to sorafenib in hepatocellular carcinoma. J Zhejiang Univ Sci B. 2014;15:713–9. CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Gluskin JS, Chegai F, Monti S, Squillaci E, Mannelli L. Hepatocellular carcinoma and diffusion-weighted MRI: detection and evaluation of treatment response. J Cancer. 2016;7:1565–70. CrossRefPubMedPubMedCentral Gluskin JS, Chegai F, Monti S, Squillaci E, Mannelli L. Hepatocellular carcinoma and diffusion-weighted MRI: detection and evaluation of treatment response. J Cancer. 2016;7:1565–70. CrossRefPubMedPubMedCentral
22.
23.
Zurück zum Zitat Zhang XY, Sun YS, Tang L, Xue WC, Zhang XP. Correlation of diffusion-weighted imaging data with apoptotic and proliferation indexes in CT26 colorectal tumor homografts in balb/c mouse. J Magn Reson Imaging. 2011;33:1171–6. CrossRefPubMed Zhang XY, Sun YS, Tang L, Xue WC, Zhang XP. Correlation of diffusion-weighted imaging data with apoptotic and proliferation indexes in CT26 colorectal tumor homografts in balb/c mouse. J Magn Reson Imaging. 2011;33:1171–6. CrossRefPubMed
24.
Zurück zum Zitat Tsai CS, Chen FH, Wang CC, Huang HL, Jung SM, Wu CJ, et al. Macrophages from irradiated tumors express higher levels of iNOS, arginase-I and COX-2, and promote tumor growth. Int J Radiat Oncol Biol Phys. 2007;68:499–507. CrossRef Tsai CS, Chen FH, Wang CC, Huang HL, Jung SM, Wu CJ, et al. Macrophages from irradiated tumors express higher levels of iNOS, arginase-I and COX-2, and promote tumor growth. Int J Radiat Oncol Biol Phys. 2007;68:499–507. CrossRef
25.
Zurück zum Zitat Rades D, Stalpers LJ, Veninga T, Hoskin PJ. Spinal reirradiation after short-course RT for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys. 2005;63:872–5. CrossRefPubMed Rades D, Stalpers LJ, Veninga T, Hoskin PJ. Spinal reirradiation after short-course RT for metastatic spinal cord compression. Int J Radiat Oncol Biol Phys. 2005;63:872–5. CrossRefPubMed
26.
Zurück zum Zitat Chiang CS, Fu SY, Wang SC, Yu CF, Chen FH, Lin CM, et al. Irradiation promotes an m2 macrophage phenotype in tumor hypoxia. Front Oncol. 2012;2:89. CrossRefPubMedPubMedCentral Chiang CS, Fu SY, Wang SC, Yu CF, Chen FH, Lin CM, et al. Irradiation promotes an m2 macrophage phenotype in tumor hypoxia. Front Oncol. 2012;2:89. CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Di Maggio FM, Minafra L, Forte GI, Cammarata FP, Lio D, Messa C, et al. Portrait of inflammatory response to ionizing radiation treatment. J Inflamm (Lond). 2015;12:14. CrossRef Di Maggio FM, Minafra L, Forte GI, Cammarata FP, Lio D, Messa C, et al. Portrait of inflammatory response to ionizing radiation treatment. J Inflamm (Lond). 2015;12:14. CrossRef
28.
29.
Zurück zum Zitat Schaue D, Jahns J, Hildebrandt G, Trott KR. Radiation treatment of acute inflammation in mice. Int J Radiat Biol. 2005;81:657–67. CrossRef Schaue D, Jahns J, Hildebrandt G, Trott KR. Radiation treatment of acute inflammation in mice. Int J Radiat Biol. 2005;81:657–67. CrossRef
30.
Zurück zum Zitat Kern P, Keilholz L, Forster C, Seegenschmiedt MH, Sauer R, Herrmann M. In vitro apoptosis in peripheral blood mononuclear cells induced by low-dose radiotherapy displays a discontinuous dose-dependence. Int J Radiat Biol. 1999;75:995–1003. CrossRef Kern P, Keilholz L, Forster C, Seegenschmiedt MH, Sauer R, Herrmann M. In vitro apoptosis in peripheral blood mononuclear cells induced by low-dose radiotherapy displays a discontinuous dose-dependence. Int J Radiat Biol. 1999;75:995–1003. CrossRef
32.
Zurück zum Zitat Rincon M. Interleukin-6: from an inflammatory marker to a target for inflammatory diseases. Trends Immunol. 2012;33:571–7. CrossRefPubMed Rincon M. Interleukin-6: from an inflammatory marker to a target for inflammatory diseases. Trends Immunol. 2012;33:571–7. CrossRefPubMed
33.
34.
Zurück zum Zitat Higashi K, Clavo AC, Wahl RL. In vitro assessment of 2-fluoro-2-deoxy-D-glucose, L-methionine and thymidine as agents to monitor the early response of a human adenocarcinoma cell line to radiotherapy. J Nucl Med. 1993;34:773–9. PubMed Higashi K, Clavo AC, Wahl RL. In vitro assessment of 2-fluoro-2-deoxy-D-glucose, L-methionine and thymidine as agents to monitor the early response of a human adenocarcinoma cell line to radiotherapy. J Nucl Med. 1993;34:773–9. PubMed
35.
Zurück zum Zitat Hu P, Cheng D, Huang T, Banizs AB, Xiao J, Liu G, et al. Evaluation of novel (64)Cu-labeled theranostic gadolinium-based Nanoprobes in HepG2 tumor-bearing nude mice. Nanoscale Res Lett. 2017;12:523. CrossRefPubMedPubMedCentral Hu P, Cheng D, Huang T, Banizs AB, Xiao J, Liu G, et al. Evaluation of novel (64)Cu-labeled theranostic gadolinium-based Nanoprobes in HepG2 tumor-bearing nude mice. Nanoscale Res Lett. 2017;12:523. CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Parashar B, Wernicke AG, Rice S, Osborne J, Singh P, Nori D, et al. Early assessment of radiation response using a novel functional imaging modality -- [18F]fluorocholine PET (FCH-PET): a pilot study. Discov Med. 2012;14:13–20. PubMedPubMedCentral Parashar B, Wernicke AG, Rice S, Osborne J, Singh P, Nori D, et al. Early assessment of radiation response using a novel functional imaging modality -- [18F]fluorocholine PET (FCH-PET): a pilot study. Discov Med. 2012;14:13–20. PubMedPubMedCentral
37.
Zurück zum Zitat Cho LP, Kim CK, Viswanathan AN. Pilot study assessing (18)F-fluorothymidine PET/CT in cervical and vaginal cancers before and after external beam radiation. Gynecol Oncol Rep. 2015;14:34–7. CrossRefPubMedPubMedCentral Cho LP, Kim CK, Viswanathan AN. Pilot study assessing (18)F-fluorothymidine PET/CT in cervical and vaginal cancers before and after external beam radiation. Gynecol Oncol Rep. 2015;14:34–7. CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Park JA, Lee YJ, Lee JW, Yoo RJ, Shin UC, Lee KC, et al. Evaluation of [(89)Zr]-oxalate as a PET tracer in inflammation, tumor, and rheumatoid arthritis models. Mol Pharm. 2016;13:2571–7. CrossRefPubMed Park JA, Lee YJ, Lee JW, Yoo RJ, Shin UC, Lee KC, et al. Evaluation of [(89)Zr]-oxalate as a PET tracer in inflammation, tumor, and rheumatoid arthritis models. Mol Pharm. 2016;13:2571–7. CrossRefPubMed
Metadaten
Titel
Diffusion-weighted MRI and 18F-FDG PET correlation with immunity in early radiotherapy response in BNL hepatocellular carcinoma mouse model: timeline validation
verfasst von
Yi-Hsiu Chung
Ching-Fang Yu
Shao-Chieh Chiu
Han Chiu
Shin-Ting Hsu
Ching-Rong Wu
Chung-Lin Yang
Ji-Hong Hong
Tzu-Chen Yen
Fang-Hsin Chen
Publikationsdatum
24.05.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 8/2019
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-019-04318-3

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