Imaging CXCR4 receptors expression for staging multiple myeloma by using ⁶⁸Ga-Pentixafor PET/CT: comparison with...

⁶⁸Ga-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 ⁶⁸Ga-Pentixafor PET/CT for imaging CXCR4 expression in MM and compared results with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT.

34 (21M; 13F; median age = 57.5 years) treatment naive multiple myeloma patients were recruited. All the patients underwent ¹⁸F-FDG PET/CT and ⁶⁸Ga-Pentixafor PET/CT imaging. Freshly prepared ⁶⁸Ga-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).

⁶⁸Ga-Pentixafor PET/CT showed higher disease extent than seen on ¹⁸F-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 ⁶⁸Ga-Pentixafor PET/CT as compared to ¹⁸F-FDG PET/CT values (2.9; IQR = 4.0). Both the techniques detected extramedullary lesions in six patients. On the other hand, ⁶⁸Ga-Pentixafor detected medullary lesions in five, whereas, ¹⁸F-FDG PET in three patients. Further, only ⁶⁸Ga-Pentixafor TBR_max correlated significantly (ρ = 0.421; 0.013) with bone marrow plasma cell percentage. ⁶⁸Ga-Pentixafor PET upstaged more number (9/29) of patients as compared to (4/29) ¹⁸F-FDG PET imaging. On the other hand, ¹⁸F-FDG PET down-staged 9/29, whereas ⁶⁸Ga-Pentixafor PET downstaged only 3/29 patients.

⁶⁸Ga-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 ⁶⁸Ga-Pentixafor/¹⁸F-FDG PET/CT imaging may help in determining the tumor heterogeneity in MM.

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.