PURPOSE: This study employed 3'-deoxy-3'-[(18)F]-fluorothymidine ([(18)F]FLT) microPET scanning to assess the treatment response of histone deacetylase inhibitors (HDACi), e.g., N1-hydroxy-N8-phenyloctanediamide (SAHA) and its iodinated derivative ISAHA, in a hepatoma mouse model. PROCEDURES: The in vitro cytotoxicity of HDACi in various hepatoma cell lines was determined by MTT assay and flow cytometry. ISAHA and SAHA were used to treat HepG2 hepatoma xenograft-bearing mice. The treatment responses were characterized in terms of tumor burden, microPET imaging, and immunohistochemical staining of tumor sections. RESULTS: ISAHA effectively inhibited HepG2 hepatoma cell survival and tumor growth. A significantly reduced tumor uptake during HDACi treatment was noticed in [(18)F]FLT microPET imaging, which was consistent with the findings in immunohistochemical staining. CONCLUSIONS: ISAHA can suppress tumor cell proliferation both in vitro and in vivo. [(18)F]FLT PET is a promising modality for evaluating the in vivo therapeutic efficacy of HDACi at the early stage of treatment.
PURPOSE: This study employed 3'-deoxy-3'-[(18)F]-fluorothymidine ([(18)F]FLT) microPET scanning to assess the treatment response of histone deacetylase inhibitors (HDACi), e.g., N1-hydroxy-N8-phenyloctanediamide (SAHA) and its iodinated derivative ISAHA, in a hepatomamouse model. PROCEDURES: The in vitro cytotoxicity of HDACi in various hepatoma cell lines was determined by MTT assay and flow cytometry. ISAHA and SAHA were used to treat HepG2 hepatoma xenograft-bearing mice. The treatment responses were characterized in terms of tumor burden, microPET imaging, and immunohistochemical staining of tumor sections. RESULTS:ISAHA effectively inhibited HepG2 hepatoma cell survival and tumor growth. A significantly reduced tumor uptake during HDACi treatment was noticed in [(18)F]FLT microPET imaging, which was consistent with the findings in immunohistochemical staining. CONCLUSIONS:ISAHA can suppress tumor cell proliferation both in vitro and in vivo. [(18)F]FLT PET is a promising modality for evaluating the in vivo therapeutic efficacy of HDACi at the early stage of treatment.
Authors: M Margarida Bernardo; Yonghong Meng; Jaron Lockett; Gregory Dyson; Alan Dombkowski; Alexander Kaplun; Xiaohua Li; Shuping Yin; Sijana Dzinic; Mary Olive; Ivory Dean; David Krass; Kamiar Moin; R Daniel Bonfil; Michael Cher; Wael Sakr; Shijie Sheng Journal: Genes Cancer Date: 2011-11
Authors: Eric H Rubin; Nancy G B Agrawal; Evan J Friedman; Pamela Scott; Kathryn E Mazina; Linda Sun; Lihong Du; Justin L Ricker; Stanley R Frankel; Keith M Gottesdiener; John A Wagner; Marian Iwamoto Journal: Clin Cancer Res Date: 2006-12-01 Impact factor: 12.531
Authors: William Kevin Kelly; Owen A O'Connor; Lee M Krug; Judy H Chiao; Mark Heaney; Tracy Curley; Barbara MacGregore-Cortelli; William Tong; J Paul Secrist; Lawrence Schwartz; Stacy Richardson; Elaina Chu; Semra Olgac; Paul A Marks; Howard Scher; Victoria M Richon Journal: J Clin Oncol Date: 2005-05-16 Impact factor: 44.544
Authors: Wm Kevin Kelly; Victoria M Richon; Owen O'Connor; Tracy Curley; Barbara MacGregor-Curtelli; William Tong; Mark Klang; Lawrence Schwartz; Stacie Richardson; Eddie Rosa; Marija Drobnjak; Carlos Cordon-Cordo; Judy H Chiao; Richard Rifkind; Paul A Marks; Howard Scher Journal: Clin Cancer Res Date: 2003-09-01 Impact factor: 12.531