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...

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Bibliographic Details
Published in:Molecular imaging 2021, Vol.2021, p.6660358-6660358
Main Authors: Yeh, Skye Hsin-Hsien, Lin, Ming Hsien, Leo Garcia Flores, I. I., Mukhopadhyay, Uday, Young, Danial, Ogawa, Kazuma, Jeong, Jeong-Hwan, Tong, William, Gelovani, Juri G., Fukumitsu, Nobuyoshi
Format: Article
Language:English
Subjects:
Accumulation
Acetylation
Anticancer properties
Cancer therapies
Cell culture
Chemotherapy
Cisplatin
Computed tomography
Decision making
Epidermal growth factor receptors
Fluorine isotopes
Gene deletion
Histone deacetylase
Histone H3
Histones
Hydroxamic acid
Lung cancer
Lung carcinoma
Medical imaging
Metastases
Non-small cell lung carcinoma
Positron emission
Positron emission tomography
Radioisotopes
Xenografts
Xenotransplantation
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Summary: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.
ISSN:1536-0121
1535-3508
1536-0121
DOI:10.1155/2021/6660358