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. E. Hudson; Leonard G. Luyt; Christopher L. Pin; Michael S. Kovacs; James Koropatnick; Ting-Yim Lee

doi:10.1117/12.2216905

29 March 2016 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. E. Hudson, Leonard G. Luyt, Christopher L. Pin, Michael S. Kovacs, James Koropatnick, Ting-Yim Lee

Author Affiliations +

Proceedings Volume 9788, Medical Imaging 2016: Biomedical Applications in Molecular, Structural, and Functional Imaging; 978814 (2016) https://doi.org/10.1117/12.2216905
Event: SPIE Medical Imaging, 2016, San Diego, California, United States

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.

Citation Download Citation

Fiona Li, Sung Ju Cho, Lihai Yu, Robert H. E. Hudson, Leonard G. Luyt, Christopher L. Pin, Michael S. Kovacs, James Koropatnick, and Ting-Yim Lee "Evaluation of 6-([¹⁸F] fluoroacetamido)-1-hexanoic-anilide (¹⁸F-FAHA) as imaging probe in tumor xenograft mice model", Proc. SPIE 9788, Medical Imaging 2016: Biomedical Applications in Molecular, Structural, and Functional Imaging, 978814 (29 March 2016); https://doi.org/10.1117/12.2216905

ACCESS THE FULL ARTICLE

INSTITUTIONAL
Select your institution to access the SPIE Digital Library.

SELECT YOUR INSTITUTION

PERSONAL
Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.

PERSONAL SIGN IN

No SPIE Account? Create one

PURCHASE THIS CONTENT

SUBSCRIBE TO DIGITAL LIBRARY

50 downloads per 1-year subscription

Members: $195

Non-members: $335 ADD TO CART

25 downloads per 1 - year subscription

Members: $145

Non-members: $250 ADD TO CART

PURCHASE SINGLE ARTICLE

Includes PDF, HTML & Video, when available

Members: $17.00

Non-members: $21.00 ADD TO CART

PROCEEDINGS
8 PAGES

DOWNLOAD PAPER SAVE TO MY LIBRARY

GET CITATION

RIGHTS & PERMISSIONS

Get copyright permission Get copyright permission on Copyright Marketplace

KEYWORDS

Tumors

Positron emission tomography

Melanoma

Cancer

Breast

Data modeling

Medical research

Show All Keywords

Keywords/Phrases

Search In:

Publication Years