Head-to-Head Comparison of 68Ga-PentixaFor PET/CT and FDG PET/CT for Detecting Hematologic and Solid Cancers: A Systematic Review and Meta-Analysis

Background: Numerous studies have shown superiority of PET/CT using the chemokine-targeted tracer 68Ga-PentixaFor over FDG PECT/CT in oncologic evaluation, although outcomes have varied across tumor types. Objective: This study aimed to conduct a head-to-head comparison of 68Ga-PentixaFor PET/CT and FDG PET/CT for detecting hematologic malignancies and solid tumors. Evidence Acquisition: PubMed and Embase databases were searched through March 4, 2024 for studies reporting a head-to-head comparison of the detection performance of 68Ga-PentixaFor PET/CT and FDG PET/CT in patients with cancer. Data were extracted from studies on a patient basis for each test in terms of detection rate, SUVmax, and target-to-background ratio (TBR). The two tests were compared separately for hematologic malignancies and solid tumors. Evidence Synthesis: The meta-analysis included 28 studies (15 of hematologic malignancies, 13 of solid cancers), with a total of 493 patients who underwent both tests. For hematologic malignancies, 68Ga-PentixaFor PET/CT, compared with FDG PET/CT, showed significantly higher detection rate overall (relative risk [RR]=1.19, p<.001) and for bone marrow involvement (RR=1.69, p<.001) but no significant difference for extramedullary involvement (RR=1.10, p=.88); 68Ga-PentixaFor PET/CT, compared with FDG PET/CT, showed significantly higher SUVmax overall (mean difference [MD]=2.26, p<.001) for bone marrow involvement (MD=4.75, p<.001), and for extramedullary involvement (MD=5.88, p<.001), as well as significantly higher TBR (MD=1.28, p=.03). For solid tumors, 68Ga-PentixaFor PET/CT, compared with FDG PET/CT, showed significantly lower detection rate overall (RR=0.73, p=.005), but no significant difference for primary lesions (RR=0.83, p=.11), lymph node metastases (RR=0.86, p=.035), or distant metastases (RR=0.64, p=.13); 68Ga-PentixaFor PET/CT, compared with FDG PET/CT, showed significantly lower SUVmax (MD=-8.79, p<.001) and TBR (MD=-3.35, p<.001). Conclusion: In head-to-head comparison, 68Ga-PentixaFor PET/CT outperformed FDG PET/CT in hematologic malignancies, whereas FDG PET/CT outperformed 68Ga-PentixaFor PET/CT in solid tumors. Clinical Impact: The findings can help guide the selection of optimal imaging strategies in patients with cancer.