CXCR4-Directed PET/CT with [68Ga]Pentixafor in Central Nervous System Lymphoma: A Comparison with [18F]FDG PET/CT

Mol Imaging Biol. 2022 Jun;24(3):416-424. doi: 10.1007/s11307-021-01664-3. Epub 2021 Oct 14.

Abstract

Purpose: This study aimed to evaluate the value of [68 Ga]Pentixafor PET/CT for the detection of lesions in central nervous system lymphoma (CNSL) patients before chemotherapy, during treatment and suspected CSNL recurrence, compared with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT).

Procedures: Twenty-six patients with newly or previously diagnosed CNSL who underwent [68 Ga]Pentixafor PET/CT were included retrospectively. Histopathological results, magnetic resonance imaging (MRI), and follow-up were used as the standard reference. The accuracy of lesion detection, maximum standardized uptake value (SUVmax) of tumors, and ratio of tumor-to-normal brain (T/N) with [68 Ga]Pentixafor PET/CT were calculated and compared to those obtained with [18F]FDG PET/CT. CXCR4 expression was analyzed through immunohistochemistry.

Results: Of 26 patients, 18 were newly diagnosed with a total of 23 lesions, 4 had recurrent with 4 lesions, and 4 underwent a mid-term treatment assessment after 4 cycles of chemotherapy (3 achieved complete response (CR), 1 experienced progressive disease (PD) with a total of 8 lesions). Thirty-five lesions were all clearly detected with favorable contrast by [68 Ga]Pentixafor PET/CT (accuracy, 100%), consistent with the results of contrast-enhanced magnetic resonance imaging (CE-MRI). The SUVmax of positive lesions in [68 Ga]Pentixafor PET/CT was correlated with tumor size (r = 0.555, P = 0.001). In 21 patients, compared with [18F]FDG PET/CT, [68 Ga]Pentixafor PET/CT showed a remarkably higher T/N ratio (21.93 ± 10.77 vs 4.29 ± 2.16, P = 0.000) and detected 5 more lesions in the mid-term treatment assessment of patients (P = 0.026). The CXCR4 expression of CNSL lesions was correlated with SUVmax of [68 Ga]Pentixafor PET/CT (r = 0.772, P = 0.000).

Conclusions: CXCR4-directed PET/CT using [68 Ga]Pentixafor, with excellent tumor-to-background contrast, might be a more promising agent for the detection of lesions in CNSL patients than [18F]FDG PET/CT.

Trial registration: ClinicalTrials.gov NCT04504526.

Keywords: C-X-C-motif chemokine receptor 4 (CXCR4); Central nervous system lymphoma (CNSL); MRI; [18F]FDG; [68 Ga]Pentixafor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Central Nervous System
  • Coordination Complexes
  • Fluorodeoxyglucose F18* / metabolism
  • Gallium Radioisotopes
  • Humans
  • Lymphoma* / diagnostic imaging
  • Lymphoma* / drug therapy
  • Peptides, Cyclic
  • Positron Emission Tomography Computed Tomography / methods
  • Receptors, CXCR4
  • Retrospective Studies

Substances

  • 68Ga-pentixafor
  • CXCR4 protein, human
  • Coordination Complexes
  • Gallium Radioisotopes
  • Peptides, Cyclic
  • Receptors, CXCR4
  • Fluorodeoxyglucose F18

Associated data

  • ClinicalTrials.gov/NCT04504526