In Vivo Evaluation of the Combined Anticancer Effects of Cisplatin and SAHA in Nonsmall Cell Lung Carcinoma Using [18F]FAHA and [18F]FDG PET/CT Imaging
Combining standard drugs with low doses of histone deacetylase inhibitors (HDACIs) is a promising strategy to increase the efficacy of chemotherapy. The ability of well-tolerated doses of HDACIs that act as chemosensitizers for platinum-based chemotherapeutics has recently been proven in many types...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2021-01-01
|
| Series: | Molecular Imaging |
| Online Access: | http://dx.doi.org/10.1155/2021/6660358 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832544487631486976 |
|---|---|
| author | Skye Hsin-Hsien Yeh Ming Hsien Lin I. I. Leo Garcia Flores Uday Mukhopadhyay Danial Young Kazuma Ogawa Jeong-Hwan Jeong William Tong Juri G. Gelovani Nobuyoshi Fukumitsu |
| author_facet | Skye Hsin-Hsien Yeh Ming Hsien Lin I. I. Leo Garcia Flores Uday Mukhopadhyay Danial Young Kazuma Ogawa Jeong-Hwan Jeong William Tong Juri G. Gelovani Nobuyoshi Fukumitsu |
| author_sort | Skye Hsin-Hsien Yeh |
| collection | DOAJ |
| description | Combining standard drugs with low doses of histone deacetylase inhibitors (HDACIs) is a promising strategy to increase the efficacy of chemotherapy. The ability of well-tolerated doses of HDACIs that act as chemosensitizers for platinum-based chemotherapeutics has recently been proven in many types and stages of cancer in vitro and in vivo. Detection of changes in HDAC activity/expression may provide important prognostic and predictive information and influence treatment decision-making. Use of [18F] FAHA, a HDAC IIa-specific radionuclide, for molecular imaging may enable longitudinal, noninvasive assessment of HDAC activity/expression in metastatic cancer. We evaluated the synergistic anticancer effects of cisplatin and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in xenograft models of nonsmall cell lung cancer (NSCLC) using [18F] FAHA and [18F] FDG PET/CT imaging. Cisplatin alone significantly increased [18F] FAHA accumulation and reduced [18F] FDG accumulation in H441 and PC14 xenografts; coadministration of cisplatin and SAHA resulted in the opposite effects. Immunochemical staining for acetyl-histone H3 confirmed the PET/CT imaging findings. Moreover, SAHA had a more significant effect on the acetylome in PC14 (EGFR exon 19 deletion mutation) xenografts than H441 (wild-type EGFR and KRAS codon 12 mutant) xenografts. In conclusion, [18F] FAHA enables quantitative visualization of HDAC activity/expression in vivo, thus, may represent a clinically useful, noninvasive tool for the management of patients who may benefit from synergistic anticancer therapy. |
| format | Article |
| id | doaj-art-717de13e351940bda6cf81ed80224c83 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-717de13e351940bda6cf81ed80224c832025-02-03T10:12:43ZengSAGE PublishingMolecular Imaging1536-01212021-01-01202110.1155/2021/66603586660358In Vivo Evaluation of the Combined Anticancer Effects of Cisplatin and SAHA in Nonsmall Cell Lung Carcinoma Using [18F]FAHA and [18F]FDG PET/CT ImagingSkye Hsin-Hsien Yeh0Ming Hsien Lin1I. I. Leo Garcia Flores2Uday Mukhopadhyay3Danial Young4Kazuma Ogawa5Jeong-Hwan Jeong6William Tong7Juri G. Gelovani8Nobuyoshi Fukumitsu9Brain Research Center, National Yang Ming Chaio Tung University, Taipei, TaiwanDepartment of Nuclear Medicine, Camillian Saint Mary’s Hospital Luodong, Yilan, TaiwanRadiomedix, Inc., Houston, USACyclotron Research Facility, Center for Advanced Biomedical Imaging, U.T.M.D. Anderson Cancer Center, Houston, USACyclotron Research Facility, Center for Advanced Biomedical Imaging, U.T.M.D. Anderson Cancer Center, Houston, USAInstitute for Frontier Science Initiative, Kanazawa University, Kanazawa, JapanDepartment of Nuclear Medicine, Chonbuk National University Medical School & Hospital, Republic of KoreaCyclotron Research Facility, Center for Advanced Biomedical Imaging, U.T.M.D. Anderson Cancer Center, Houston, USAOncology, Neurosurgery, OBGYN, Biomedical Engineering, Wayne State University, Detroit, USADepartment of Radiation Oncology, Kobe Proton Center, Kobe, JapanCombining standard drugs with low doses of histone deacetylase inhibitors (HDACIs) is a promising strategy to increase the efficacy of chemotherapy. The ability of well-tolerated doses of HDACIs that act as chemosensitizers for platinum-based chemotherapeutics has recently been proven in many types and stages of cancer in vitro and in vivo. Detection of changes in HDAC activity/expression may provide important prognostic and predictive information and influence treatment decision-making. Use of [18F] FAHA, a HDAC IIa-specific radionuclide, for molecular imaging may enable longitudinal, noninvasive assessment of HDAC activity/expression in metastatic cancer. We evaluated the synergistic anticancer effects of cisplatin and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in xenograft models of nonsmall cell lung cancer (NSCLC) using [18F] FAHA and [18F] FDG PET/CT imaging. Cisplatin alone significantly increased [18F] FAHA accumulation and reduced [18F] FDG accumulation in H441 and PC14 xenografts; coadministration of cisplatin and SAHA resulted in the opposite effects. Immunochemical staining for acetyl-histone H3 confirmed the PET/CT imaging findings. Moreover, SAHA had a more significant effect on the acetylome in PC14 (EGFR exon 19 deletion mutation) xenografts than H441 (wild-type EGFR and KRAS codon 12 mutant) xenografts. In conclusion, [18F] FAHA enables quantitative visualization of HDAC activity/expression in vivo, thus, may represent a clinically useful, noninvasive tool for the management of patients who may benefit from synergistic anticancer therapy.http://dx.doi.org/10.1155/2021/6660358 |
| spellingShingle | Skye Hsin-Hsien Yeh Ming Hsien Lin I. I. Leo Garcia Flores Uday Mukhopadhyay Danial Young Kazuma Ogawa Jeong-Hwan Jeong William Tong Juri G. Gelovani Nobuyoshi Fukumitsu In Vivo Evaluation of the Combined Anticancer Effects of Cisplatin and SAHA in Nonsmall Cell Lung Carcinoma Using [18F]FAHA and [18F]FDG PET/CT Imaging Molecular Imaging |
| title | In Vivo Evaluation of the Combined Anticancer Effects of Cisplatin and SAHA in Nonsmall Cell Lung Carcinoma Using [18F]FAHA and [18F]FDG PET/CT Imaging |
| title_full | In Vivo Evaluation of the Combined Anticancer Effects of Cisplatin and SAHA in Nonsmall Cell Lung Carcinoma Using [18F]FAHA and [18F]FDG PET/CT Imaging |
| title_fullStr | In Vivo Evaluation of the Combined Anticancer Effects of Cisplatin and SAHA in Nonsmall Cell Lung Carcinoma Using [18F]FAHA and [18F]FDG PET/CT Imaging |
| title_full_unstemmed | In Vivo Evaluation of the Combined Anticancer Effects of Cisplatin and SAHA in Nonsmall Cell Lung Carcinoma Using [18F]FAHA and [18F]FDG PET/CT Imaging |
| title_short | In Vivo Evaluation of the Combined Anticancer Effects of Cisplatin and SAHA in Nonsmall Cell Lung Carcinoma Using [18F]FAHA and [18F]FDG PET/CT Imaging |
| title_sort | in vivo evaluation of the combined anticancer effects of cisplatin and saha in nonsmall cell lung carcinoma using 18f faha and 18f fdg pet ct imaging |
| url | http://dx.doi.org/10.1155/2021/6660358 |
| work_keys_str_mv | AT skyehsinhsienyeh invivoevaluationofthecombinedanticancereffectsofcisplatinandsahainnonsmallcelllungcarcinomausing18ffahaand18ffdgpetctimaging AT minghsienlin invivoevaluationofthecombinedanticancereffectsofcisplatinandsahainnonsmallcelllungcarcinomausing18ffahaand18ffdgpetctimaging AT iileogarciaflores invivoevaluationofthecombinedanticancereffectsofcisplatinandsahainnonsmallcelllungcarcinomausing18ffahaand18ffdgpetctimaging AT udaymukhopadhyay invivoevaluationofthecombinedanticancereffectsofcisplatinandsahainnonsmallcelllungcarcinomausing18ffahaand18ffdgpetctimaging AT danialyoung invivoevaluationofthecombinedanticancereffectsofcisplatinandsahainnonsmallcelllungcarcinomausing18ffahaand18ffdgpetctimaging AT kazumaogawa invivoevaluationofthecombinedanticancereffectsofcisplatinandsahainnonsmallcelllungcarcinomausing18ffahaand18ffdgpetctimaging AT jeonghwanjeong invivoevaluationofthecombinedanticancereffectsofcisplatinandsahainnonsmallcelllungcarcinomausing18ffahaand18ffdgpetctimaging AT williamtong invivoevaluationofthecombinedanticancereffectsofcisplatinandsahainnonsmallcelllungcarcinomausing18ffahaand18ffdgpetctimaging AT juriggelovani invivoevaluationofthecombinedanticancereffectsofcisplatinandsahainnonsmallcelllungcarcinomausing18ffahaand18ffdgpetctimaging AT nobuyoshifukumitsu invivoevaluationofthecombinedanticancereffectsofcisplatinandsahainnonsmallcelllungcarcinomausing18ffahaand18ffdgpetctimaging |