Imaging of C-X-C Motif Chemokine Receptor 4 Expression in 690 Patients with Solid or Hematologic Neoplasms using <sup>68</sup>Ga-PentixaFor PET
Andreas K. Buck, Alexander Haug, Niklas Dreher, Alessandro Lambertini, Takahiro Higuchi, Constantin Lapa, Alexander Weich, Martin G. Pomper, Hans‐Jürgen Wester, Anja Zehnder, Andreas Schirbel, Samuel Samnick, Marcus Hacker, Verena Pichler, Stefanie Hahner, Martin Faßnacht, Hermann Einsele, Sebastian E. Serfling, Rudolf A. Werner
Abstract
<b>Background:</b> In recent years, molecular imaging adressing the C-X-C motif chemokine receptor 4 (CXCR4) has increasingly been utilized 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> 690 patients with a variety of neoplasms underwent a total of 777 PET/CT scans with <sup>68</sup>Ga-PentixaFor, serving as CXCR4-specific radioligand. A semiquantitative target lesion (TL) analysis was conducted [providing maximum standardized uptake values (SUV<sub>max</sub>) and target-to-blood pool ratio (TBR), defined as SUV<sub>max</sub> (from TL) divided by mean SUV (from blood pool)]. The applied specific activity (in MBq/µg) was compared to semi-quantitative 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<sub>max</sub> > 12) was found in multiple myeloma (MM; <i>n</i> = 113), followed by adrenocortical carcinoma (<i>n</i> = 30), mantle cell lymphoma (MCL; <i>n</i> = 20), adrenocortical adenoma (<i>n</i> = 6) and small cell lung cancer (SCLC; <i>n</i> = 12). Providing information on image contrast, comparable results for TBR were recorded, with TBR (>8) in MM, MCL and acute lymphoblastoid leukemia (<i>n</i> = 6). When comparing specific activity with semiquantitative parameters, no significant correlation was found for SUV<sub>max</sub> or TBR (P ≥ 0.612). <b>Conclusion:</b> In this large cohort, <sup>68</sup>Ga-PentixaFor demonstrated high image contrast in a variety of neoplasms, particularly for hematologic malignancies, SCLC and adrenocortical neoplasms. The present analysis may provide a roadmap to detect patients who may benefit from CXCR4-targeted therapies.