Chemokine receptor-targeted PET/CT provides superior diagnostic performance in newly diagnosed marginal zone lymphoma patients: a head-to-head comparison with [18F]FDG

Abstract

Background: In patients with marginal zone lymphoma (MZL), [¹⁸F]FDG PET/CT provided inconsistent diagnostic accuracy. C-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in MZL and thus, may emerge as novel theranostic target. We aimed to evaluate the diagnostic performance of CXCR4-targeting [⁶⁸Ga]Ga-PentixaFor when compared to [¹⁸F]FDG PET/CT in MZL.

Methods: Thirty-two untreated MZL patients (nodal, n = 17; extranodal, n = 13; splenic, n = 2) received [⁶⁸Ga]Ga-PentixaFor and [¹⁸F]FDG PET/CT within median 2 days. We performed a visual and quantitative analysis of the total lymphoma volume by measuring maximum/peak standardized uptake values (SUV_max/peak), and calculating target-to-background ratios (TBR, defined as lesion-based SUV_peak divided by SUV_mean from blood pool). Visual comparisons for both radiotracers were carried out for all target lesions (TL), and quantitative analysis of concordant TL evident on both scans. Last, MZL subtype analyses were also conducted.

Results: On a patient-based level, [⁶⁸Ga]Ga-PentixaFor identified MZL manifestations in 32 (100%) subjects (vs. [¹⁸F]FDG, 25/32 [78.1%]). Of the 256 identified TL, 127/256 (49.6%) manifestations were evident only on CXCR4-directed imaging, while only 7/256 (2.7%) were identified on [¹⁸F]FDG but missed by [⁶⁸Ga]Ga-PentixaFor. In the remaining 122/256 (47.7%) concordant TL, [⁶⁸Ga]Ga-PentixaFor consistently provided increased metrics when compared to [¹⁸F]FDG: SUV_max, 10.3 (range, 2.53-37.2) vs. 5.72 (2.32-37.0); SUV_peak, 6.23 (1.58-25.7) vs. 3.87 (1.54-27.7); P < 0.01, respectively. Concordant TL TBR on [⁶⁸Ga]Ga-PentixaFor (median, 3.85; range, 1.05-16.0) was also approximately 1.8-fold higher relative to [¹⁸F]FDG (median, 2.08; range, 0.81-28.8; P < 0.01). Those findings on image contrast, however, were driven by nodal MZL (P < 0.01), and just missed significance for extranodal MZL (P = 0.06).

Conclusions: In newly diagnosed MZL patients, [⁶⁸Ga]Ga-PentixaFor identified more sites of disease when compared to [¹⁸F]FDG, irrespective of MZL subtype. Quantitative PET parameters including TBR were also higher on [⁶⁸Ga]Ga-PentixaFor PET/CT, suggesting improved diagnostic read-out using chemokine receptor-targeted imaging.

Keywords: C-X-C motif chemokine receptor; CXCR4; Marginal zone lymphoma; PET; [18F]FDG; [68Ga]Ga-PentixaFor.