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 SUVmax 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 (SUVmax_L3) of 11C-acetate, as imaging indicator for MM tumor burden, showed a strong correlation with plasma cell infiltration (r=0.723, P