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Targeting Paraprotein Biosynthesis for Non-Invasive Characterization of Myeloma Biology

Please always quote using this URN: urn:nbn:de:bvb:20-opus-111319
  • Purpose Multiple myeloma is a hematologic malignancy originating from clonal plasma cells. Despite effective therapies, outcomes are highly variable suggesting marked disease heterogeneity. The role of functional imaging for therapeutic management of myeloma, such as positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG-PET), remains to be determined. Although some studies already suggested a prognostic value of 18F-FDG-PET, more specific tracers addressing hallmarks of myeloma biology, e.g. paraprotein biosynthesis, arePurpose Multiple myeloma is a hematologic malignancy originating from clonal plasma cells. Despite effective therapies, outcomes are highly variable suggesting marked disease heterogeneity. The role of functional imaging for therapeutic management of myeloma, such as positron emission tomography with 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG-PET), remains to be determined. Although some studies already suggested a prognostic value of 18F-FDG-PET, more specific tracers addressing hallmarks of myeloma biology, e.g. paraprotein biosynthesis, are needed. This study evaluated the amino acid tracers L-methyl-[11C]-methionine (11C-MET) and [18F]-fluoroethyl-L-tyrosine (18F-Fet) for their potential to image myeloma and to characterize tumor heterogeneity. Experimental Design To study the utility of 11C-MET, 18F-Fet and 18F-FDG for myeloma imaging, time activity curves were compared in various human myeloma cell lines (INA-6, MM1.S, OPM-2) and correlated to cell-biological characteristics, such as marker gene expression and immunoglobulin levels. Likewise, patient-derived CD138+ plasma cells were characterized regarding uptake and biomedical features. Results Using myeloma cell lines and patient-derived CD138+ plasma cells, we found that the relative uptake of 11C-MET exceeds that of 18F-FDG 1.5- to 5-fold and that of 18F-Fet 7- to 20-fold. Importantly, 11C-MET uptake significantly differed between cell types associated with worse prognosis (e.g. t(4;14) in OPM-2 cells) and indolent ones and correlated with intracellular immunoglobulin light chain and cell surface CD138 and CXCR4 levels. Direct comparison of radiotracer uptake in primary samples further validated the superiority of 11C-MET. Conclusion These data suggest that 11C-MET might be a versatile biomarker for myeloma superior to routine functional imaging with 18F-FDG regarding diagnosis, risk stratification, prognosis and discrimination of tumor subtypes.show moreshow less

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Metadaten
Author: Katharina Lückerath, Constantin Lapa, Annika Spahmann, Gerhard Jörg, Samuel Samnick, Andreas Rosenwald, Herrmann Einsele, Stefan Knop, Andreas Buck
URN:urn:nbn:de:bvb:20-opus-111319
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Nuklearmedizin
Medizinische Fakultät / Pathologisches Institut
Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Year of Completion:2013
Source:PLoS ONE 8(12): e84840. doi:10.1371/journal.pone.0084840
DOI:https://doi.org/10.1371/journal.pone.0084840
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Antibodies; Myeloma cells; Myelomas; Positron emission tomography; biosynthesis; bone marrow cells; cell staining; lesions
Release Date:2015/03/30
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2014
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung