In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma.
Bottom Line: We evaluated the novel CXCR4 probe [(68)Ga]Pentixafor for in vivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [(68)Ga]Pentixafor PET provided images with excellent specificity and contrast.In 10 of 14 patients with advanced MM [(68)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [(18)F]fluorodeoxyglucose PET/CT scans were rated visually positive.Assessment of blood counts and standard CD34(+) flow cytometry did not reveal significant blood count changes associated with tracer application.
Affiliation: III. Medical Department of Hematology and Medical Oncology, Technische Universität München, Munich, Germany.Show MeSH
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Mentions: To evaluate the suitability of [68Ga]Pentixafor for in vivo imaging of MM in patients and for its usefulness to select patients for future CXCR4-directed treatments, we visually analyzed 14 patients with histologically proven, advanced MM. The patient characteristics are shown in Table1. All patients gave written informed consent for receiving the [68Ga]Pentixafor PET as well as undergoing a standard [18F]FDG PET. Representative images of one [68Ga]Pentixafor PET-positive patient are shown in Fig3A–D. Representative images of one [68Ga]Pentixafor PET-negative patient are shown in Supplementary Fig S4. In summary, 9 of 14 (64%) [18F]FDG scans were rated visually positive, whereas 10 of 14 (71%) [68Ga]Pentixafor scans revealed disease manifestations (Fig4A). Visual comparison of [18F]FDG and [68Ga]Pentixafor scans resulted in comparable findings in 3 (21%) patients. In 7 patients (50%), the [68Ga]Pentixafor signal was superior to [18F]FDG identifying more tumor lesions, whereas in 2 patients (14%), [18F]FDG provided additional information compared to [68Ga]Pentixafor. In the remaining 2 patients (14%), [68Ga]Pentixafor and [18F]FDG provided complementary information regarding the detection of myeloma manifestations (Fig4B). More than three lesions were reported in 8 of 14 FDG scans and 8 of 14 [68Ga]Pentixafor PET scans. Extramedullary disease (EMD) was detected in 3 [68Ga]Pentixafor scans and in 2 [18F]FDG PET scans. In one patient, [68Ga]Pentixafor but not [18F]FDG identified EMD. In comparison with the PET scans, only 1 of 14 CT scans did not show MM manifestations resulting in 13 of 14 (93%) positive scans. More than three lesions were described in 10 of 14 patients, whereas EMD was only reported in 1 patient. An exemplary patient where [68Ga]Pentixafor imaging provided superior information is shown in Supplementary Fig S5.
Affiliation: III. Medical Department of Hematology and Medical Oncology, Technische Universität München, Munich, Germany.