Detecting CXCR4 Expression in Meningioma on ⁶⁸Ga-Pentixafor PET/MRI

The C-X-C chemokine receptor 4 (CXCR4) is crucial for tumor proliferation, migration, and angiogenesis in many different cancers. Recently, ⁶⁸Ga-pentixafor, a radiotracer comprising a synthetic, cyclic pentapeptide analog of stromal cell–derived factor 1, a ligand for CXCR4, has been successfully introduced for assessment of hematologic malignancies, including lymphomas of the body and central nervous system, myeloma, and leukemia (1,2). Furthermore, ⁶⁸Ga-pentixafor uptake has been described in various solid tumors but not yet in meningioma.

We report the case of a 67-y-old woman with newly diagnosed primary central nervous system lymphoma who was referred for ⁶⁸Ga-pentixafor PET/MRI (NCT05093335) 2 d after MRI was performed with intravenously injected gadopentetate dimeglumine (Magnevist; Bayer Healthcare Pharmaceuticals). PET imaging was acquired for 15 min starting 15 min after intravenous injection of 150 MBq of ⁶⁸Ga-pentixafor on a hybrid device (Signa PET/MR; GE Healthcare). PET demonstrated a homogeneously enhancing lesion in the right temporal lobe with an SUV_max of 5.3 (Fig. 1). Incidentally, slightly lower uptake, with an SUV_max of 4.8, was observed in a dura-based extraaxial homogeneously enhancing mass in the left middle cranial fossa, a known meningioma.

• Download figure
• Open in new tab
• Download powerpoint

FIGURE 1.

Contrast-enhanced T1-weighted MR images showing enhancing lesions with focal ⁶⁸Ga-pentixafor uptake on axial PET/MRI (A) and on maximum-intensity-projection PET (B), corresponding to biopsy-proven lymphoma (orange arrows) and known meningioma (blue arrows).

Here, we show that ⁶⁸Ga-pentixafor can detect not only central nervous system lymphoma but also meningioma with a high tumor-to-background activity ratio on PET, given the minimal uptake of this radiotracer in brain parenchyma. A recent analysis in 55 meningioma specimens showed that CXCR4 messenger RNA was expressed in 43 (78%) of the tumor specimens, and CXCR4 stimulation led to extracellular signal-regulated protein kinase 1 and 2 phosphorylation/activation and cell proliferation (3). CXCR4 and stromal cell–derived factor 1 were often detected in the same tumor tissues, suggesting an autocrine–paracrine feedback loop potentially promoting the phenotypic behavior of the tumor, such as the ability to grow autonomously.

Our findings suggest that ⁶⁸Ga-pentixafor PET may be useful for delineation of meningioma and for elucidating biologic characteristics and that, especially in treatment-refractory meningiomas, ⁶⁸Ga-pentixafor PET may guide CXCR4-based theranostic approaches with pentixather that were previously evaluated in blood cancers (4).

• © 2023 by the Society of Nuclear Medicine and Molecular Imaging.

• Received for publication November 1, 2022.
• Revision received November 7, 2022.