Abstract
OBJECTIVES: (68)Ga-Pentixafor positron emission tomography (PET) imaging targets CXCR4 expression which is overexpressed in multiple myeloma (MM). In this study, we evaluated the diagnostic utility of (68)Ga-Pentixafor PET/CT for imaging CXCR4 expression in MM and compared results with (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT. METHODS: 34 (21M; 13F; median age = 57.5 years) treatment naive multiple myeloma patients were recruited. All the patients underwent (18)F-FDG PET/CT and (68)Ga-Pentixafor PET/CT imaging. Freshly prepared (68)Ga-Pentixafor (148-185 MBq) was injected intravenously and whole-body PET/CT (low-dose CT) was acquired at 1 h post-injection. The pattern of uptake (diffuse, focal or mixed) and the mean SUV(max) value of all the lesions (when lesions were ≤5) or of the five most tracer avid lesions (when lesions was >5) were evaluated. Tumor to background ratio (TBR(max)) was calculated for both the tracers. Durie Salmon plus staging (DSPS) was used for disease staging on PET and the results were compared with International staging system (ISS). RESULTS: (68)Ga-Pentixafor PET/CT showed higher disease extent than seen on (18)F-FDG PET/CT in 23/34 patients (68.0%), lesser disease extent in 2/34 (6%) and similar disease extent in 9/34 (26%) patients. Significantly (p < 0.001) higher TBR(max) values (5.7; IQR 8.8) were observed on (68)Ga-Pentixafor PET/CT as compared to (18)F-FDG PET/CT values (2.9; IQR = 4.0). Both the techniques detected extramedullary lesions in six patients. On the other hand, (68)Ga-Pentixafor detected medullary lesions in five, whereas, (18)F-FDG PET in three patients. Further, only (68)Ga-Pentixafor TBR(max) correlated significantly (ρ = 0.421; 0.013) with bone marrow plasma cell percentage. (68)Ga-Pentixafor PET upstaged more number (9/29) of patients as compared to (4/29) (18)F-FDG PET imaging. On the other hand, (18)F-FDG PET down-staged 9/29, whereas (68)Ga-Pentixafor PET downstaged only 3/29 patients. CONCLUSION: (68)Ga-Pentixafor PET/CT evaluated the whole-body disease burden of CXCR4 receptors non-invasively which is not possible by tissue sampling methods. This novel PET tracer has also implication for disease staging. Dual (68)Ga-Pentixafor/(18)F-FDG PET/CT imaging may help in determining the tumor heterogeneity in MM. ADVANCES IN KNOWLEDGE: This CXCR4 targeting PET tracer has a promising role in the development of CXCR4 targeting theranostics and also for response assessment to these therapies including the conventional treatment.