Assessment of DNA Double-Strand Breaks in Blood Lymphocytes after Whole-Body Radiation Exposure in Patients with Neuroendocrine Tumors Undergoing 177Lu-Octreotate Therapy Abstract #616
Introduction: Peptide receptor radionuclide therapy using somatostatin receptor-binding peptides, such as 177Lu-Octreotate (LuTate), has been clinically proven to be effective in treating patients with inoperable neuroendocrine tumors. Despite the rather high radiation exposure, only few side effects have been reported. However, blood cells are very sensitive to radiation. Therefore, it is important to determine how much radiation they received. Recently, the detection by immunofluorescence of the phosphorylation of the histone variant H2AX (γ‐H2AX) has been established as a reliable and sensitive technique to monitor DNA double-strand breaks (DSBs) in blood lymphocytes.
Aim(s): To investigate the kinetics of DSBs in blood lymphocytes in patients with neuroendocrine tumors undergoing up to four LuTate treatments.
Materials and methods: Ten patients received between 6‐11 GBq of LuTate with an administered activity adapted to the burden of a somatostatin receptor-expressing tumor and renal function. We measured γ‐H2AX foci up to 72 hrs post‐treatment, and correlated these numbers with 177Lu radioactivity clearance data in serum.
Conference: 10th Annual ENETS Conference (2013)
Category: Basic Science - Genetics, epigenetics, miRNAs
Presenting Author: Dr Delphine Denoyer
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Keywords: DNA methylation, CpG dinucleotides, genome-wide, differentially methylated region (DMR) References: Duerr EM et al Defining molecular classifications and targets in gastroenteropancreatic neuroendocrine tumors through DNA microarray analysis. Endocr Relat Cancer. 2008 Mar;15(1):243-56 Kulke MH et al O6 –methylguanine DNA methyltransferase deficiency and response to temozolomide-based therapy in patients with neuroendocrine tumours. Clin Cancer Res 2009; 15(1): 338-345 Mikkelsen TS et al Dissecting direct reprogramming through integrative genomic analysis. Nature. 2008 454(7200):49-55. Shen L et al Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer. Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18654-9.