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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

MET-PET reveals very early treatment response in vivoMM.1S tumors in Nod.Scid mice were imaged at baseline and 24 h after administration of Bz using MET- and FDG-PET, respectively. (A) Coronal views of an exemplary mouse. (B) Mean TBRs of FDG and MET at baseline (bl), in the control (ctrl) and treatment (Bz) group. (C) Relative change in tracer-uptake by tumors (mean TBR) in individual mice 24 h post treatment initiation compared to baseline. (D) FACS analyses evaluating dead cells (top left), CD138 (top right) and intracellular Ig light chain (bottom right) expression. Proliferation (bottom left) was assessed histologically by Ki-67 staining on paraffin embedded sections. Horizontal lines indicate the median in each group. Asterisk indicate statistical significance (p < 0.02). Differences in (D) are not statistically significant.
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Figure 5: MET-PET reveals very early treatment response in vivoMM.1S tumors in Nod.Scid mice were imaged at baseline and 24 h after administration of Bz using MET- and FDG-PET, respectively. (A) Coronal views of an exemplary mouse. (B) Mean TBRs of FDG and MET at baseline (bl), in the control (ctrl) and treatment (Bz) group. (C) Relative change in tracer-uptake by tumors (mean TBR) in individual mice 24 h post treatment initiation compared to baseline. (D) FACS analyses evaluating dead cells (top left), CD138 (top right) and intracellular Ig light chain (bottom right) expression. Proliferation (bottom left) was assessed histologically by Ki-67 staining on paraffin embedded sections. Horizontal lines indicate the median in each group. Asterisk indicate statistical significance (p < 0.02). Differences in (D) are not statistically significant.

Mentions: Using FDG-PET, no differences between TBRs of control (mean increase in TBR to 144 ± 79%; median of mean TBR 2.22, range 1.3–6.1, n = 17) or treatment group (mean increase in TBR to 141 ± 66%; median absolute TBR 2.53, range 1.0–5.9, p = 0.897; n = 15) could be detected (Figure 5A, 5B, 5C). Interestingly, molecular analyses of tumors resected after the last PET-scan did not show clear differences but only a slight tendency in the treatment-group to less living cells, proliferative activity, intracellular immunoglobulin light chain levels or CD138 expression (Figure 5D).


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)

MET-PET reveals very early treatment response in vivoMM.1S tumors in Nod.Scid mice were imaged at baseline and 24 h after administration of Bz using MET- and FDG-PET, respectively. (A) Coronal views of an exemplary mouse. (B) Mean TBRs of FDG and MET at baseline (bl), in the control (ctrl) and treatment (Bz) group. (C) Relative change in tracer-uptake by tumors (mean TBR) in individual mice 24 h post treatment initiation compared to baseline. (D) FACS analyses evaluating dead cells (top left), CD138 (top right) and intracellular Ig light chain (bottom right) expression. Proliferation (bottom left) was assessed histologically by Ki-67 staining on paraffin embedded sections. Horizontal lines indicate the median in each group. Asterisk indicate statistical significance (p < 0.02). Differences in (D) are not statistically significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: MET-PET reveals very early treatment response in vivoMM.1S tumors in Nod.Scid mice were imaged at baseline and 24 h after administration of Bz using MET- and FDG-PET, respectively. (A) Coronal views of an exemplary mouse. (B) Mean TBRs of FDG and MET at baseline (bl), in the control (ctrl) and treatment (Bz) group. (C) Relative change in tracer-uptake by tumors (mean TBR) in individual mice 24 h post treatment initiation compared to baseline. (D) FACS analyses evaluating dead cells (top left), CD138 (top right) and intracellular Ig light chain (bottom right) expression. Proliferation (bottom left) was assessed histologically by Ki-67 staining on paraffin embedded sections. Horizontal lines indicate the median in each group. Asterisk indicate statistical significance (p < 0.02). Differences in (D) are not statistically significant.
Mentions: Using FDG-PET, no differences between TBRs of control (mean increase in TBR to 144 ± 79%; median of mean TBR 2.22, range 1.3–6.1, n = 17) or treatment group (mean increase in TBR to 141 ± 66%; median absolute TBR 2.53, range 1.0–5.9, p = 0.897; n = 15) could be detected (Figure 5A, 5B, 5C). Interestingly, molecular analyses of tumors resected after the last PET-scan did not show clear differences but only a slight tendency in the treatment-group to less living cells, proliferative activity, intracellular immunoglobulin light chain levels or CD138 expression (Figure 5D).

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