Imaging of C-X-C Motif Chemokine Receptor 4 Expression in 690 Patients with Solid or Hematologic Neoplasms Using 68Ga-Pentixafor PET

Abstract

In recent years, molecular imaging addressing the C-X-C motif chemokine receptor 4 (CXCR4) has increasingly been used in various clinical settings. Here, we aimed to assess radiopharmaceutical uptake and image contrast to determine the most relevant clinical applications for CXCR4-directed imaging. We also investigated the impact of specific activity on scan contrast. Methods: Patients (n 5 690) with a variety of neoplasms underwent a total of 777 PET/CT scans with 68Ga-Pentixa-for, serving as the CXCR4-specific radioligand. A semiquantitative target lesion analysis was conducted (providing SUVmax and target-to-blood pool ratio [TBR], defined as SUVmax [from target lesion] divided by SUVmean [from blood pool]). The applied specific activity (in MBq/mg) was compared with semiquantitative assessments. Results: Of the 777 scans, 242 did not show discernible uptake in disease sites, leaving 535 PET scans (68.9%) for further analysis. Very high tracer uptake (SUVmax. 12) was found in multiple myeloma (n 5 113), followed by adrenocortical carcinoma (n 5 30), mantle cell lymphoma (n 5 20), adrenocortical adenoma (n 5 6), and small cell lung cancer (n 5 12). Providing information on image contrast, comparable results for TBR were recorded, with TBR (.8) in multiple myeloma, mantle cell lymphoma, and acute lymphoblastoid leukemia (n 5 6). When comparing specific activity with semiquantitative parameters, no significant correlation was found for SUVmax or TBR (P $ 0.612). Conclusion: In this large cohort, 68Ga-Pentixafor demonstrated high image contrast in a variety of neoplasms, particularly for hematologic malignancies, small cell lung cancer, and adrenocortical neoplasms. The present analysis may provide a roadmap for detecting patients who may benefit from CXCR4-targeted therapies.