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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

Treatment-induced alterations of further hallmarks of MM biology do not parallel changes in tracer-uptake(A) Relative proliferation rate as assessed by CFSE dilution (GeoMean; n = 5). (B) Intracellular levels of either λ- (MM.1S, OPM-2) or κ- (INA-6) immunoglobulin light chains were determined by FACS analysis (GeoMean) using anti-Ig λ-FITC- and anti-Ig κ-APC antibodies (n = 5). Background-corrected means ± standard deviation related to that of untreated controls are shown. Asterisk indicate statistically significant differences (p < 0.02).
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Figure 3: Treatment-induced alterations of further hallmarks of MM biology do not parallel changes in tracer-uptake(A) Relative proliferation rate as assessed by CFSE dilution (GeoMean; n = 5). (B) Intracellular levels of either λ- (MM.1S, OPM-2) or κ- (INA-6) immunoglobulin light chains were determined by FACS analysis (GeoMean) using anti-Ig λ-FITC- and anti-Ig κ-APC antibodies (n = 5). Background-corrected means ± standard deviation related to that of untreated controls are shown. Asterisk indicate statistically significant differences (p < 0.02).

Mentions: All three proteasome inhibitors uniformly reduced the proliferative activity of MM cell lines by 50–60% compared to untreated controls (p < 0.02) (Figure 3A). However, the extent of this reduction did not parallel the change in uptake of either MET or FDG (Supplementary Figure 1B).


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)

Treatment-induced alterations of further hallmarks of MM biology do not parallel changes in tracer-uptake(A) Relative proliferation rate as assessed by CFSE dilution (GeoMean; n = 5). (B) Intracellular levels of either λ- (MM.1S, OPM-2) or κ- (INA-6) immunoglobulin light chains were determined by FACS analysis (GeoMean) using anti-Ig λ-FITC- and anti-Ig κ-APC antibodies (n = 5). Background-corrected means ± standard deviation related to that of untreated controls are shown. Asterisk indicate statistically significant differences (p < 0.02).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Treatment-induced alterations of further hallmarks of MM biology do not parallel changes in tracer-uptake(A) Relative proliferation rate as assessed by CFSE dilution (GeoMean; n = 5). (B) Intracellular levels of either λ- (MM.1S, OPM-2) or κ- (INA-6) immunoglobulin light chains were determined by FACS analysis (GeoMean) using anti-Ig λ-FITC- and anti-Ig κ-APC antibodies (n = 5). Background-corrected means ± standard deviation related to that of untreated controls are shown. Asterisk indicate statistically significant differences (p < 0.02).
Mentions: All three proteasome inhibitors uniformly reduced the proliferative activity of MM cell lines by 50–60% compared to untreated controls (p < 0.02) (Figure 3A). However, the extent of this reduction did not parallel the change in uptake of either MET or FDG (Supplementary Figure 1B).

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