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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

Assessing early response to Bz in CD138+-plasma cells using MET or FDG(A) CD138+-plasma cells from individual patients were or were not treated with Bz for 24 h, subsequently incubated with either FDG or MET for 60 min and intracellular radioactivity was quantified using a gamma-counter. Relative uptake of background- and decay-corrected samples was expressed as mean cpm per 1000 cells. Horizontal lines indicate the median in each group. The table gives the uptake values (cpm/1000 cells) for each patient. (B) Cell surface expression of CD138 and intracellular levels of Ig light chains in control and treated primary MM cells are shown as GeoMean (n = 4).
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Figure 4: Assessing early response to Bz in CD138+-plasma cells using MET or FDG(A) CD138+-plasma cells from individual patients were or were not treated with Bz for 24 h, subsequently incubated with either FDG or MET for 60 min and intracellular radioactivity was quantified using a gamma-counter. Relative uptake of background- and decay-corrected samples was expressed as mean cpm per 1000 cells. Horizontal lines indicate the median in each group. The table gives the uptake values (cpm/1000 cells) for each patient. (B) Cell surface expression of CD138 and intracellular levels of Ig light chains in control and treated primary MM cells are shown as GeoMean (n = 4).

Mentions: To validate our findings in a more physiological setting, we isolated primary CD138+-plasma cells from MM patients (see Supplementary Table 1 for patients' characteristics), split the samples into four groups and analyzed radiotracer uptake: (i) untreated/MET, (ii) untreated/FDG, (iii) 24 h Bz/FDG, (iv) 24 h Bz/MET. In agreement with the results obtained in MM cell lines, addition of Bz decreased MET retention markedly in 6/7 cases (remaining sample: higher uptake in presence of Bz); in contrast, FDG uptake increased in 4/6 samples and decreased in only 2/6 (Figure 4A). In the 4 samples that contained enough cells for further FACS analyses, neither levels of intracellular immunoglobulin light chains nor expression of CD138 were impacted at this early time point (24 h drug exposure) (Figure 4B).


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)

Assessing early response to Bz in CD138+-plasma cells using MET or FDG(A) CD138+-plasma cells from individual patients were or were not treated with Bz for 24 h, subsequently incubated with either FDG or MET for 60 min and intracellular radioactivity was quantified using a gamma-counter. Relative uptake of background- and decay-corrected samples was expressed as mean cpm per 1000 cells. Horizontal lines indicate the median in each group. The table gives the uptake values (cpm/1000 cells) for each patient. (B) Cell surface expression of CD138 and intracellular levels of Ig light chains in control and treated primary MM cells are shown as GeoMean (n = 4).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Assessing early response to Bz in CD138+-plasma cells using MET or FDG(A) CD138+-plasma cells from individual patients were or were not treated with Bz for 24 h, subsequently incubated with either FDG or MET for 60 min and intracellular radioactivity was quantified using a gamma-counter. Relative uptake of background- and decay-corrected samples was expressed as mean cpm per 1000 cells. Horizontal lines indicate the median in each group. The table gives the uptake values (cpm/1000 cells) for each patient. (B) Cell surface expression of CD138 and intracellular levels of Ig light chains in control and treated primary MM cells are shown as GeoMean (n = 4).
Mentions: To validate our findings in a more physiological setting, we isolated primary CD138+-plasma cells from MM patients (see Supplementary Table 1 for patients' characteristics), split the samples into four groups and analyzed radiotracer uptake: (i) untreated/MET, (ii) untreated/FDG, (iii) 24 h Bz/FDG, (iv) 24 h Bz/MET. In agreement with the results obtained in MM cell lines, addition of Bz decreased MET retention markedly in 6/7 cases (remaining sample: higher uptake in presence of Bz); in contrast, FDG uptake increased in 4/6 samples and decreased in only 2/6 (Figure 4A). In the 4 samples that contained enough cells for further FACS analyses, neither levels of intracellular immunoglobulin light chains nor expression of CD138 were impacted at this early time point (24 h drug exposure) (Figure 4B).

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