Ms. Fiona Li Profile

Fiona Li

at Western Univ

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Proceedings Article | 29 March 2016 Paper

Evaluation of 6-([18F] fluoroacetamido)-1-hexanoic-anilide (18F-FAHA) as imaging probe in tumor xenograft mice model

Fiona Li, Sung Ju Cho, Lihai Yu, Robert H. Hudson, Leonard Luyt, Christopher Pin, Michael Kovacs, James Koropatnick, Ting-Yim Lee

Proceedings Volume 9788, 978814 (2016) https://doi.org/10.1117/12.2216905

KEYWORDS: Positron emission tomography, Image analysis, Modeling, Cancer, Melanoma, Mouse models, Oncology, Breast, Tumors, Medical research, Data modeling, Tissues

Read 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.

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