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

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).

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 (SUV_max) 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.

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 SUV_max 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 SUV_max of [⁶⁸ Ga]Pentixafor PET/CT (r = 0.772, P = 0.000).

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.