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11C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma.

Lückerath K, Lapa C, Albert C, Herrmann K, Jörg G, Samnick S, Einsele H, Knop S, Buck AK - Oncotarget (2015)

Bottom Line: Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression.No significant differences were detected thus early with FDG.Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy.

View Article: PubMed Central - PubMed

Affiliation: University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg, Germany.

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.

No MeSH data available.


Related in: MedlinePlus

Monitoring response to proteasome inhibitors in MM cell lines using MET or FDGCells were treated for 48 h with either proteasome inhibitor or left untreated before intracellular radioactivity after incubation with MET (top) or FDG (bottom) was quantified using a gamma-counter. Relative uptake of background- and decay-corrected triplicate-samples was expressed as cpm per 1000 cells (mean ± sem; n = 4).
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Figure 1: Monitoring response to proteasome inhibitors in MM cell lines using MET or FDGCells were treated for 48 h with either proteasome inhibitor or left untreated before intracellular radioactivity after incubation with MET (top) or FDG (bottom) was quantified using a gamma-counter. Relative uptake of background- and decay-corrected triplicate-samples was expressed as cpm per 1000 cells (mean ± sem; n = 4).

Mentions: To evaluate the suitability of MET and FDG for monitoring response to anti-MM therapy, MM cell lines were treated with either of three proteasome inhibitors, bortezomib (Bz; Velcade®), ixazomib (Iz; MLN9708) or carfilzomib (Cz; Kyprolis®). 48 h after drug addition, the capacity to store MET or FDG, respectively, was assessed in uptake experiments. In agreement with our previously published data (14), MET uptake in untreated control cells was higher than that of FDG. Comparing untreated with treated cells, a significant reduction in tracer-retention could be observed for all treatments at any time points analyzed with remaining MET-uptake slightly higher than that of FDG (Figure 1).


11C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma.

Lückerath K, Lapa C, Albert C, Herrmann K, Jörg G, Samnick S, Einsele H, Knop S, Buck AK - Oncotarget (2015)

Monitoring response to proteasome inhibitors in MM cell lines using MET or FDGCells were treated for 48 h with either proteasome inhibitor or left untreated before intracellular radioactivity after incubation with MET (top) or FDG (bottom) was quantified using a gamma-counter. Relative uptake of background- and decay-corrected triplicate-samples was expressed as cpm per 1000 cells (mean ± sem; n = 4).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480763&req=5

Figure 1: Monitoring response to proteasome inhibitors in MM cell lines using MET or FDGCells were treated for 48 h with either proteasome inhibitor or left untreated before intracellular radioactivity after incubation with MET (top) or FDG (bottom) was quantified using a gamma-counter. Relative uptake of background- and decay-corrected triplicate-samples was expressed as cpm per 1000 cells (mean ± sem; n = 4).
Mentions: To evaluate the suitability of MET and FDG for monitoring response to anti-MM therapy, MM cell lines were treated with either of three proteasome inhibitors, bortezomib (Bz; Velcade®), ixazomib (Iz; MLN9708) or carfilzomib (Cz; Kyprolis®). 48 h after drug addition, the capacity to store MET or FDG, respectively, was assessed in uptake experiments. In agreement with our previously published data (14), MET uptake in untreated control cells was higher than that of FDG. Comparing untreated with treated cells, a significant reduction in tracer-retention could be observed for all treatments at any time points analyzed with remaining MET-uptake slightly higher than that of FDG (Figure 1).

Bottom Line: Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression.No significant differences were detected thus early with FDG.Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy.

View Article: PubMed Central - PubMed

Affiliation: University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg, Germany.

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.

No MeSH data available.


Related in: MedlinePlus