Head-to-Head Comparison Between [18F]FDG and [68Ga]Ga-Pentixafor PET/CT in Multiple Myeloma: A Systematic Review and Meta-Analysis

Background/objective: Multiple myeloma (MM) is a hematological malignancy characterized by the proliferation of clonal plasma cells. While [18F]FDG PET/CT is widely established for assessing disease extent, bone involvement, and treatment response in MM, novel molecular imaging targets like CXCR4 (e.g., using [68Ga]Ga-Pentixafor) have emerged to offer potentially superior sensitivity and theranostic applications. The aim of this manuscript is to systematically review and compare the diagnostic performance, expressed as detection rates, of CXCR4-targeted PET/CT versus [18F]FDG PET/CT in patients with MM. Methods: A systematic literature search was conducted across major databases (PubMed/MEDLINE, Embase, and the Cochrane Library) for head-to-head comparative studies evaluating both [18F]FDG and [68Ga]Ga-Pentixafor PET/CT in MM patients. Risk of bias and study quality were assessed using the QUADAS-2 tool. Results: Eleven studies were collected, amounting to a total of 347 patients. A patient-based analysis showed that [68Ga]Ga-Pentixafor had a higher detection rate than [18F]FDG PET/CT (86.3%, 95% CI: 80.3–92.3% vs 60.9%, 95% CI: 42.5–79.4%). In a descriptive analysis, mean lesion SUVmax values reported across individual studies were generally higher with [68Ga]Ga-Pentixafor PET/CT than with [18F]FDG PET/CT. Conclusions: [68Ga]Ga-Pentixafor PET/CT may serve as a robust alternative or complementary imaging modality to [18F]FDG PET/CT in MM. It could also be helpful for selection in CXCR4-directed theranostic pathways, but more high-quality studies are warranted.