title: [18F]FLT-PET to predict pharmacodynamic and clinical response to cetuximab therapy in Ménétrier's disease.
abstract: Molecular imaging biomarkers of proliferation hold great promise for quantifying response to personalized medicine. One such approach utilizes the positron emission tomography (PET) tracer 3'-deoxy-3'[18F]-fluorothymidine ([18F]FLT), an investigational agent whose uptake reflects thymidine salvage-dependent DNA synthesis. The goal of this study was to evaluate [18F]FLT-PET in the setting of Ménétrier's disease (MD), a rare, premalignant hyperproliferative disorder of the stomach treatable with cetuximab therapy. Over 15 months, a patient with confirmed MD underwent cetuximab therapy and was followed with sequential [18F]FLT-PET. For comparison to MD, an [18F]FLT-PET study was conducted in another patient to quantify uptake in a normal stomach. Prior to cetuximab therapy, stomach tissue in MD was easily visualized with [18F]FLT-PET, with pre-treatment uptake levels exceeding normal stomach uptake by approximately fourfold. Diminished [18F]FLT-PET in MD was observed following the initial and subsequent doses of cetuximab and correlated with clinical resolution of the disease. To our knowledge, this study reports the first clinical use of [18F]FLT-PET to assess proliferation in a premalignant disorder. We illustrate that the extent of MD involvement throughout the stomach could be easily visualized using [18F]FLT-PET, and that response to cetuximab could be followed quantitatively and non-invasively in sequential [18F]FLT-PET studies. Thus, [18F]FLT-PET appears to have potential to monitor response to treatment in this and potentially other hyperproliferative disorders.
authors: Vanderbilt University Institute of Imaging Science, Vanderbilt University, 1161 21st Ave. S., AA1105 MCN, Nashville, TN 37232-2310, USA.
authors: Eliot T
authors: ET
authors: McKinley
authors: R Adam
authors: RA
authors: Smith
authors: Jarred P
authors: JP
authors: Tanksley
authors: Mary Kay
authors: MK
authors: Washington
authors: Ronald
authors: R
authors: Walker
authors: Robert J
authors: RJ
authors: Coffey
authors: H Charles
authors: HC
authors: Manning
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D000068818:Cetuximab; D015224:Dideoxynucleosides; D005260:Female; D005758:Gastritis, Hypertrophic / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015224:Dideoxynucleosides; C002854:alovudine; D000068818:Cetuximab