title: 11C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma.
abstract: Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers 11C-Methionine (paraprotein-biosynthesis) and 18F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138+ plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM.1S tumors underwent MET- and FDG-μPET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30-79% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET- but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future.
authors.affiliation: University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Lückerath
authors.affiliation: University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: Lapa
authors.affiliation: University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Albert
authors.affiliation: University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg, Germany.
authors.forename: Ken
authors.initials: K
authors.lastname: Herrmann
authors.affiliation: University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Jörg
authors.affiliation: University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg, Germany.
authors.forename: Samuel
authors.initials: S
authors.lastname: Samnick
authors.affiliation: University Hospital Wuerzburg, Department of Internal Medicine II, Division of Hematology and Oncology, Wuerzburg, Germany.
authors.forename: Herrmann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: University Hospital Wuerzburg, Department of Internal Medicine II, Division of Hematology and Oncology, Wuerzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Knop
authors.affiliation: University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg, Germany.
authors.forename: Andreas K
authors.initials: AK
authors.lastname: Buck
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D008715:Methionine / Q000032:analysis*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000032:analysis*; D016019:Survival Analysis
chemical_list: D019275:Radiopharmaceuticals; C086242:carbon-11 methionine; D008715:Methionine
keywords: 11C-Methionine-PET; molecular imaging; multiple myeloma; treatment response