¹¹C-acetate PET/CT has a significantly higher correlation with FISH test than ¹⁸F-FDG PET/CT in risk stratification of multiple myeloma

Objectives: FISH (fluorescence in situ hybridization test) is the most common genetics test for multiple myeloma (MM), capable of risk stratification, prediction of disease progression, and management decision for patients with smoldering MM (SMM) and MM. We previously reported that ¹¹C-acetate PET/CT is a continuum surrogate imaging marker for the detection of active MM lesions and measurement of MM tumor burden. In this prospective study, we aim to extend our investigation on ¹¹C-acetate PET/CT for risk stratification of newly diagnosed MM patients by correlation study with MM FISH results.

Methods: From Oct 2013 to July 2018, 104 newly identified MM patients (M: 57, F: 47; age range: 33-89 y, mean: 63.7±11.5 y) were referred to dual-tracer (¹¹C-acetate & ¹⁸F-FDG) PET/CT for treatment planning. The diagnosis was confirmed by bone marrow biopsy with evidence of abnormal plasma cell >=10%. Interphase TARGET FISH test was performed for detection of 4 chromosome aberrations: 17p13.1 (p53) deletion, t(4;14) translocation, t(14;16) translocation and chromosome lq21 (CKS1B) amplification of the plasma cells on marrow blood samples. Detection positive for any of the 4 chromosome aberrations was considered “high-risk MM”, otherwise “low-risk MM”. PET/CT was analyzed on focal bone lesions (FBL) and marrow activity (semi-quantified by SUV_max of L3 for plasma cell burden). Kaplan-Meier univariate analysis was used to evaluate the predictive significance in MM risk stratification of 4 PET/CT parameters: 1. number of FBL by ¹¹C-acetate, 2. number of FBL by ¹⁸F-FDG, 3. marrow activity of ¹¹C-acetate, 4. marrow activity of ¹⁸F-FDG. ROC analysis was performed on the significant risk predictors to define the cut-off values for high-risk MM.

Results: The reported plasma cell infiltration by bone marrow examination ranged from 11 to 95% (mean=(43±24)%). Marrow activity (SUV_max_L3) of ¹¹C-acetate, as imaging indicator for MM tumor burden, showed a strong correlation with plasma cell infiltration (r=0.723, P<0.05), whereas ¹⁸F-FDG marrow activity showed a weak correlation (r=0.539, P<0.05). TARGET FISH analysis identified 56/104 high-risk and 48/104 low-risk MM. Univariate analysis of the above mentioned 4 PET/CT parameters identified 2 predictors statistically significant for high-risk MM: 1. SUV_max_L3 of ¹¹C-acetate, which was significantly higher in high-risk versus low-risk MM (SUV_max_L3=5.53±2.20 vs 3.79±1.31, P=0.0001); 2 SUV_max_L3 of ¹⁸F-FDG, also significantly different between high-risk and low-risk MM (SUV_max_L3=3.27±1.53 vs 2.48±0.90, P=0.01). For prediction of high-risk MM, ROC-defined thresholds of SUV_max_L3 were 4.45 and 3.15 on ¹¹C-acetate and ¹⁸F-FDG PET, respectively. Nevertheless, ¹¹C-acetate PET was significantly more sensitive than ¹⁸F-FDG (76.8% vs 46.4%, P<0.05). In the 30/56 high-risk MM patients negative on ¹⁸F-FDG PET, 17/30 (56.7%) were identified by ¹¹C-acetate and the incremental value was significant (P<0.05). The specificity and AUC for identifying high-risk MM were 83.3% (40/48) vs 81.3% (39/48), and 0.818 vs 0.673 by ¹¹C-acetate and ¹⁸F-FDG PET.

Conclusions: Our data suggested that metabolic characterization with ¹¹C-acetate PET on the assessment of Acetyl CoA synthase activity in MM plasma cells was able to assess MM tumor burden as well as to identify high-risk MM patients significantly more accurate than with ¹⁸F-FDG. The ¹¹C-acetate marrow activity threshold (>=4.45) may serve as an imaging biomarker for risk stratification in treatment-naïve MM patients, and hopefully may facilitate treatment planning.