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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

Early reduction in MET uptake correlates with improved survival(A) Kaplan-Meier-curve of animals treated with bortezomib (d1-4-8-11; n = 7; green) and control group (n = 8; blue). (B) Tumor-to-background ratios of MET (top) and FDG (bottom) uptake in treatment (dashed lines)- and control (solid lines) group at baseline, 24 h, 8d and 15d after treatment initiation. Correlation of changes in MET (C) and FDG (D) uptake 24 h post treatment initiation with survival (green, responders; blue, non-responders).
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Figure 6: Early reduction in MET uptake correlates with improved survival(A) Kaplan-Meier-curve of animals treated with bortezomib (d1-4-8-11; n = 7; green) and control group (n = 8; blue). (B) Tumor-to-background ratios of MET (top) and FDG (bottom) uptake in treatment (dashed lines)- and control (solid lines) group at baseline, 24 h, 8d and 15d after treatment initiation. Correlation of changes in MET (C) and FDG (D) uptake 24 h post treatment initiation with survival (green, responders; blue, non-responders).

Mentions: In a second line of experiments, xenografted mice received MET as well as FDG scans at baseline, 24 h, at d8 (before third Bz administration) and at d15 (4 days after completion of one Bz therapy cycle) post-treatment initiation. All mice were followed up until death or a human end point was reached. Treatment with Bz significantly reduced tumor burden (Supplementary Figure 3A, 3B) and improved survival of mice (median 34 days, range 30–39 days; compared to a median of 15 days, range 7–30 days, in the control-group; p = 0.001) (Figure 6A).


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)

Early reduction in MET uptake correlates with improved survival(A) Kaplan-Meier-curve of animals treated with bortezomib (d1-4-8-11; n = 7; green) and control group (n = 8; blue). (B) Tumor-to-background ratios of MET (top) and FDG (bottom) uptake in treatment (dashed lines)- and control (solid lines) group at baseline, 24 h, 8d and 15d after treatment initiation. Correlation of changes in MET (C) and FDG (D) uptake 24 h post treatment initiation with survival (green, responders; blue, non-responders).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Early reduction in MET uptake correlates with improved survival(A) Kaplan-Meier-curve of animals treated with bortezomib (d1-4-8-11; n = 7; green) and control group (n = 8; blue). (B) Tumor-to-background ratios of MET (top) and FDG (bottom) uptake in treatment (dashed lines)- and control (solid lines) group at baseline, 24 h, 8d and 15d after treatment initiation. Correlation of changes in MET (C) and FDG (D) uptake 24 h post treatment initiation with survival (green, responders; blue, non-responders).
Mentions: In a second line of experiments, xenografted mice received MET as well as FDG scans at baseline, 24 h, at d8 (before third Bz administration) and at d15 (4 days after completion of one Bz therapy cycle) post-treatment initiation. All mice were followed up until death or a human end point was reached. Treatment with Bz significantly reduced tumor burden (Supplementary Figure 3A, 3B) and improved survival of mice (median 34 days, range 30–39 days; compared to a median of 15 days, range 7–30 days, in the control-group; p = 0.001) (Figure 6A).

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