Abstract
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Objectives: 68Ga-Pentixafor PET imaging targets CXCR4 expression which is over-expressed in multiple myeloma. In the present study, we evaluated the diagnostic utility of 68Ga-Pentixafor PET/CT for in vivo assessment of the disease extent and staging in multiple myeloma patients and compared it with 18F-FDG PET/CT.
Methods: Thirty-four (21M; 13F; median age= 57.5 years) treatment naive multiple myeloma patients were recruited. All patients underwent 18F-FDG-PET/CT and 68Ga-Pentixafor PET/CT imaging within one week interval. 68 Ga-Pentixafor was synthesized in-house using an automated GMP chemistry module (Scintomics, Germany) and 148-185 MBq of 68Ga-Pentixafor was injected intravenously followed by whole-body (Head to Toe) PET (10-12 frames) and low dose CT (CT) imaging acquired 1-h after the administration of radiotracer. To evaluate the extent of involvement, body was divided into 13 regions and number of tracer avid lesions (medullary/extramedullary) were counted in each region. The pattern of uptake (diffuse, focal or mixed) and the mean SUVmax value of all lesions (when the numer of lesions were ≤ 5) or SUVmax value of the 5 most tracer avid lesions (if number of lesions was more than 5) were evaluated. Tumor to background ratio (TBRmax) was calculated by lesion SUV/Mediastinum blood pool SUV). Durie Salmon system was used for staging on PET and results were compared with International staging system (ISS) for myeloma.
Results: The laboratory parameters are given in table-1. 68Ga-Pentixafor PET-CT showed higher disease extent than seen on 18F-FDG PET in 23/34 patients (68.0%), lesser disease extent in 2/34 (6%) and similar disease extent in 9/34 (26%) patients respectively (Figure-1). Significantly higher TBRmax values (5.7, IQR 9.1 vs 2.9, IQR =4.0, p<0.001) were obseved on 68Ga-Pentixafor PET as compared to 18F-FDG PET imaging. Both techniques detected extramedullary lesions in 6 patients. Out of these 6 patients, medullary lesions were detected by 68Ga-Pentixafor in 5 and by 18F-FDG PET in 3 patients, respectively. Significant correlation was noted between TBRmax on 68Ga-Pentixafor with the bone marrow plasma cell percentage (rho 0.421, p value 0.013) but was not significant for 18F-FDG PET (rho 0.253, p value 0.149). Nearly half of the patients had the equivalent disease stage using both both tracers compared to ISS staging. When compared to ISS, 68Ga-Pentixafor PET upstaged more number of patients (9/29) as compared to 18F-FDG PET imaging (4/29). On the other hand, 18F-FDG-PET imaging down-staged more number (9/29) of patients than that shown by 68Ga-Pentixafor PET imaging (3/29).
Conclusions: 68Ga-Pentixafor PET imaging detected more number of involved sites than 18F-FDG PET using Durie Salmon staging system in Multiple myeloma. The technique may be useful for response evaluation to CXCR4 targeting pharmacologic or endoradiotherapeutic therapies in CXCR4+ and FDG- disease variant of multiple myeloma.