The Clinical Role of CXCR4-Targeted PET on Lymphoproliferative Disorders: A Systematic Review

Background/Objectives: We conducted a comprehensive investigation to explore the pathological expression of the CXCR4 receptor in lymphoproliferative disorders (LPDs) using [⁶⁸Ga]Ga-Pentixafor PET/CT or PET/MRI technology. The PICO question was as follows: What is the diagnostic role (outcome) of [⁶⁸Ga]Ga-Pentixafor PET (intervention) in patients with LPDs (problem/population)? Methods: The study was written based on the reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines, and it was registered on the prospective register of systematic reviews (PROSPERO) website (CRD42024506866). A comprehensive computer literature search of Scopus, MEDLINE, Scholar, and Embase databases was conducted, including articles indexed up to February 2024. To the methodological evaluation of the studies used the quality assessment of diagnosis accuracy studies-2 (QUADAS-2) tool. Results: Of the 8380 records discovered, 23 were suitable for systematic review. Fifteen studies (on 571 LPD patients) focused on diagnosis and staging, and eight trials (194 LPD patients) assessed treatment response. Conclusions: The main conclusions that can be inferred from the published studies are as follows: (a) [⁶⁸Ga]Ga-Pentixafor PET may have excellent diagnostic performance in the study of several LPDs; (b) [⁶⁸Ga]Ga-Pentixafor PET may be superior to [¹⁸F]FDG or complementary in some LPDs variants and settings; (c) multiple myeloma seems to have a high uptake of [⁶⁸Ga]Ga-Pentixafor. Overall, this technique is probably suitable for imaging, staging, and follow-up on patients with LPD. Due to limited data, further studies are warranted to confirm the promising role of [⁶⁸Ga]Ga-Pantixafor in this context.