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Proceedings Paper

Evaluation of 6-([18F] fluoroacetamido)-1-hexanoic-anilide (18F-FAHA) as imaging probe in tumor xenograft mice model
Author(s): Fiona Li; Sung Ju Cho; Lihai Yu; Robert H. E. Hudson; Leonard G. Luyt; Christopher L. Pin; Michael S. Kovacs; James Koropatnick; Ting-Yim Lee
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Paper Abstract

Alteration in genetic expression is as important as gene mutation in cancer development and proliferation. Epigenetic changes affect gene expression without altering the DNA sequence. Histone deacetylase (HDAC), an enzyme facilitating histone remodelling, can lead to silencing of tumor suppressor genes making HDAC inhibitors viable anticancer drugs against tumors with increased activity of the enzyme. In this study we evaluated 18F-fluroacetamido-1-hexanoicanilide (18F-FAHA), an artificial HDAC substrate, as imaging probe of HDAC activity of human tumor xenografts in immunocompromised host mice. Human breast and melanoma cell lines, MDA-MB-468 and MDA-MB-435 respectively, known to overexpress HDAC activity were xenografted into immunocompromised mice and HDAC activity was imaged using 18F-FAHA. The melanoma group was treated with saline, SAHA (suberoylanilide hydroxamic acid, an approved anticancer HDAC inhibitor) in DMSO, or DMSO as positive control. Tracer kinetic modelling and SUV were used to estimate HDAC activity from dynamic PET data. Both breast tumor and melanoma group showed great variability in binding rate constant (BRC) of 18F-FAHA suggesting highly variable inter- and intra-tumoral HDAC activity. For the SAHA treated melanoma group, HDAC activity, as monitored by BRC of 18F-FAHA, decreased more than the two (positive and negative) control groups but not tumor growth. Our preliminary study showed that noninvasive PET imaging with 18F-FAHA has the potential to identify patients for whom treatment with HDAC inhibitors are appropriate, to assess the effectiveness of that treatment as an early marker of target reduction, and also eliminate the need for invasive tissue biopsy to individualize treatment.

Paper Details

Date Published: 29 March 2016
PDF: 8 pages
Proc. SPIE 9788, Medical Imaging 2016: Biomedical Applications in Molecular, Structural, and Functional Imaging, 978814 (29 March 2016); doi: 10.1117/12.2216905
Show Author Affiliations
Fiona Li, Western Univ. (Canada)
Robarts Research Institute (Canada)
Lawson Health Research Institute (Canada)
Sung Ju Cho, Western Univ. (Canada)
Lawson Health Research Institute (Canada)
Lihai Yu, Lawson Health Research Institute (Canada)
Robert H. E. Hudson, Western Univ. (Canada)
Leonard G. Luyt, Western Univ. (Canada)
Lawson Health Research Institute (Canada)
Christopher L. Pin, Western Univ. (Canada)
Michael S. Kovacs, Western Univ. (Canada)
Lawson Health Research Institute (Canada)
James Koropatnick, Western Univ. (Canada)
Lawson Health Research Instittue (Canada)
Ting-Yim Lee, Western Univ. (Canada)
Robarts Research Institute (Canada)
Lawson Health Research Institute (Canada)


Published in SPIE Proceedings Vol. 9788:
Medical Imaging 2016: Biomedical Applications in Molecular, Structural, and Functional Imaging
Barjor Gimi; Andrzej Krol, Editor(s)

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