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. <b>Methods:</b> Patients (<i>n</i> = 690) with a variety of neoplasms underwent a total of 777 PET/CT scans with ⁶⁸Ga-Pentixafor, serving as the CXCR4-specific radioligand. A semiquantitative target lesion analysis was conducted (providing SUV_max and target-to-blood pool ratio [TBR], defined as SUV_max [from target lesion] divided by SUV_mean [from blood pool]). The applied specific activity (in MBq/μg) was compared with semiquantitative assessments. <b>Results:</b> 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 (SUV_max > 12) was found in multiple myeloma (<i>n</i> = 113), followed by adrenocortical carcinoma (<i>n</i> = 30), mantle cell lymphoma (<i>n</i> = 20), adrenocortical adenoma (<i>n</i> = 6), and small cell lung cancer (<i>n</i> = 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 (<i>n</i> = 6). When comparing specific activity with semiquantitative parameters, no significant correlation was found for SUV_max or TBR (<i>P</i> ≥ 0.612). <b>Conclusion:</b> 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.