Orthotopic hepatocellular carcinoma: molecular imaging-monitored intratumoral hyperthermia-enhanced direct oncolytic virotherapy
Objective: To validate the feasibility of molecular imaging-monitored intratumoral radiofrequency hyperthermia (RFH) enhanced direct oncolytic virotherapy for hepatocellular carcinoma (HCC). Methods: This study included in vitro experiments using luciferase-labeled rat HCC cells and in vivo validati...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Taylor & Francis Group
2019-01-01
|
Series: | International Journal of Hyperthermia |
Subjects: | |
Online Access: | http://dx.doi.org/10.1080/02656736.2019.1569731 |
id |
doaj-4b0f3dbedf3a4bf99b3822a58d5c1f2c |
---|---|
record_format |
Article |
spelling |
doaj-4b0f3dbedf3a4bf99b3822a58d5c1f2c2020-11-25T02:39:35ZengTaylor & Francis GroupInternational Journal of Hyperthermia0265-67361464-51572019-01-0136134334910.1080/02656736.2019.15697311569731Orthotopic hepatocellular carcinoma: molecular imaging-monitored intratumoral hyperthermia-enhanced direct oncolytic virotherapyJingjing Song0Feng Zhang1Jiansong Ji2Minjiang Chen3Qiang Li4Qiaoyou Weng5Shannon Gu6Matthew J. Kogut7Xiaoming Yang8University of Washington School of MedicineUniversity of Washington School of MedicineKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Affiliated Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central HospitalKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Affiliated Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central HospitalYinzhou People’s Hospital NingboKey Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Affiliated Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Central HospitalUniversity of Washington School of MedicineUniversity of Washington School of MedicineUniversity of Washington School of MedicineObjective: To validate the feasibility of molecular imaging-monitored intratumoral radiofrequency hyperthermia (RFH) enhanced direct oncolytic virotherapy for hepatocellular carcinoma (HCC). Methods: This study included in vitro experiments using luciferase-labeled rat HCC cells and in vivo validation experiments on rat models with orthotopic HCCs. Both cells and HCCs in four groups (n = 6/group) were treated by: (1) combination therapy of oncolytic virotherapy (T-VEC) plus RFH at 42 °C for 30 min; (2) oncolytic virotherapy alone; (3) RFH alone; and (4) saline. For in vitro confirmation, confocal microscopy and bioluminescence optical imaging were used to evaluate the cell viabilities. For in vivo validation, oncolytic viruses were directly infused into rat HCCs through a multi-functional perfusion-thermal RF electrode, followed by RFH. Ultrasound and optical imaging were used to follow up size and bioluminescence signal changes of tumors overtime, which were correlated with subsequent laboratory examinations. Results: For in vitro experiments, confocal microscopy showed the lowest number of viable cells, as well as a significant decrease of bioluminescence signal intensity of cells with combination therapy group, compared to other three groups (p < .001). For in vivo experiments, ultrasound and optical imaging showed the smallest tumor volume, and significantly decreased bioluminescence signal intensity in combination therapy group compared to other three groups (p < .05), which were well correlated with pathologic analysis. Conclusion: It is feasible of using molecular imaging to guide RFH-enhanced intratumoral oncolytic virotherapy of HCC, which may open new avenues to prevent residual or recurrent disease of thermally ablated intermediate-to-large HCCs.http://dx.doi.org/10.1080/02656736.2019.1569731molecular imagingradiofrequency hyperthermiaoncolytic virushepatocellular carcinoma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jingjing Song Feng Zhang Jiansong Ji Minjiang Chen Qiang Li Qiaoyou Weng Shannon Gu Matthew J. Kogut Xiaoming Yang |
spellingShingle |
Jingjing Song Feng Zhang Jiansong Ji Minjiang Chen Qiang Li Qiaoyou Weng Shannon Gu Matthew J. Kogut Xiaoming Yang Orthotopic hepatocellular carcinoma: molecular imaging-monitored intratumoral hyperthermia-enhanced direct oncolytic virotherapy International Journal of Hyperthermia molecular imaging radiofrequency hyperthermia oncolytic virus hepatocellular carcinoma |
author_facet |
Jingjing Song Feng Zhang Jiansong Ji Minjiang Chen Qiang Li Qiaoyou Weng Shannon Gu Matthew J. Kogut Xiaoming Yang |
author_sort |
Jingjing Song |
title |
Orthotopic hepatocellular carcinoma: molecular imaging-monitored intratumoral hyperthermia-enhanced direct oncolytic virotherapy |
title_short |
Orthotopic hepatocellular carcinoma: molecular imaging-monitored intratumoral hyperthermia-enhanced direct oncolytic virotherapy |
title_full |
Orthotopic hepatocellular carcinoma: molecular imaging-monitored intratumoral hyperthermia-enhanced direct oncolytic virotherapy |
title_fullStr |
Orthotopic hepatocellular carcinoma: molecular imaging-monitored intratumoral hyperthermia-enhanced direct oncolytic virotherapy |
title_full_unstemmed |
Orthotopic hepatocellular carcinoma: molecular imaging-monitored intratumoral hyperthermia-enhanced direct oncolytic virotherapy |
title_sort |
orthotopic hepatocellular carcinoma: molecular imaging-monitored intratumoral hyperthermia-enhanced direct oncolytic virotherapy |
publisher |
Taylor & Francis Group |
series |
International Journal of Hyperthermia |
issn |
0265-6736 1464-5157 |
publishDate |
2019-01-01 |
description |
Objective: To validate the feasibility of molecular imaging-monitored intratumoral radiofrequency hyperthermia (RFH) enhanced direct oncolytic virotherapy for hepatocellular carcinoma (HCC). Methods: This study included in vitro experiments using luciferase-labeled rat HCC cells and in vivo validation experiments on rat models with orthotopic HCCs. Both cells and HCCs in four groups (n = 6/group) were treated by: (1) combination therapy of oncolytic virotherapy (T-VEC) plus RFH at 42 °C for 30 min; (2) oncolytic virotherapy alone; (3) RFH alone; and (4) saline. For in vitro confirmation, confocal microscopy and bioluminescence optical imaging were used to evaluate the cell viabilities. For in vivo validation, oncolytic viruses were directly infused into rat HCCs through a multi-functional perfusion-thermal RF electrode, followed by RFH. Ultrasound and optical imaging were used to follow up size and bioluminescence signal changes of tumors overtime, which were correlated with subsequent laboratory examinations. Results: For in vitro experiments, confocal microscopy showed the lowest number of viable cells, as well as a significant decrease of bioluminescence signal intensity of cells with combination therapy group, compared to other three groups (p < .001). For in vivo experiments, ultrasound and optical imaging showed the smallest tumor volume, and significantly decreased bioluminescence signal intensity in combination therapy group compared to other three groups (p < .05), which were well correlated with pathologic analysis. Conclusion: It is feasible of using molecular imaging to guide RFH-enhanced intratumoral oncolytic virotherapy of HCC, which may open new avenues to prevent residual or recurrent disease of thermally ablated intermediate-to-large HCCs. |
topic |
molecular imaging radiofrequency hyperthermia oncolytic virus hepatocellular carcinoma |
url |
http://dx.doi.org/10.1080/02656736.2019.1569731 |
work_keys_str_mv |
AT jingjingsong orthotopichepatocellularcarcinomamolecularimagingmonitoredintratumoralhyperthermiaenhanceddirectoncolyticvirotherapy AT fengzhang orthotopichepatocellularcarcinomamolecularimagingmonitoredintratumoralhyperthermiaenhanceddirectoncolyticvirotherapy AT jiansongji orthotopichepatocellularcarcinomamolecularimagingmonitoredintratumoralhyperthermiaenhanceddirectoncolyticvirotherapy AT minjiangchen orthotopichepatocellularcarcinomamolecularimagingmonitoredintratumoralhyperthermiaenhanceddirectoncolyticvirotherapy AT qiangli orthotopichepatocellularcarcinomamolecularimagingmonitoredintratumoralhyperthermiaenhanceddirectoncolyticvirotherapy AT qiaoyouweng orthotopichepatocellularcarcinomamolecularimagingmonitoredintratumoralhyperthermiaenhanceddirectoncolyticvirotherapy AT shannongu orthotopichepatocellularcarcinomamolecularimagingmonitoredintratumoralhyperthermiaenhanceddirectoncolyticvirotherapy AT matthewjkogut orthotopichepatocellularcarcinomamolecularimagingmonitoredintratumoralhyperthermiaenhanceddirectoncolyticvirotherapy AT xiaomingyang orthotopichepatocellularcarcinomamolecularimagingmonitoredintratumoralhyperthermiaenhanceddirectoncolyticvirotherapy |
_version_ |
1724785051308130304 |