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 = 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. 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 (SUV_max > 12) was found in multiple myeloma (n = 113), followed by adrenocortical carcinoma (n = 30), mantle cell lymphoma (n = 20), adrenocortical adenoma (n = 6), and small cell lung cancer (n = 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 = 6). When comparing specific activity with semiquantitative parameters, no significant correlation was found for SUV_max 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.

Keywords: 68Ga-Pentixafor; C-X-C motif chemokine receptor 4; CXCR4; PET.