Evaluating the diagnostic utility of [⁶⁸Ga]Ga-Pentixafor in solid tumors: a systematic review

The C-X-C motif chemokine receptor 4 (CXCR4) has emerged as a critical molecular imaging target in various malignancies due to its central role in tumor progression, metastasis, and resistance to therapy. Among the imaging modalities developed to exploit this target, [68Ga]Ga-Pentixafor—a positron emission tomography (PET) radiopharmaceutical—has shown potential in diagnostic imaging. However, its diagnostic utility in solid tumors remains relatively underexplored, particularly in comparison to the widely utilized [18F]fluorodeoxyglucose ([18F]FDG) PET/CT. Comprehensive literature search was performed across PubMed, Scopus, Web of Science and Embase, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies included those reporting CXCR4-targeted PET imaging in solid tumors, with data on lesion detection, semiquantitative uptake values including maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR). Data extraction focused on study design, patient demographics, tumor types, imaging protocols, and key findings. The quality of included studies was assessed using standardized risk-of-bias tools using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. This systematic review analyzed data from 26 studies, encompassing 831 patients with various solid malignancies to assess the diagnostic utility of [68Ga]Ga-Pentixafor PET/CT. Tracer uptake varied significantly among tumor types, with higher SUVmax values observed in adrenocortical carcinoma, small cell lung cancer, and desmoplastic small round cell tumors, while lower uptake was noted in breast cancer, glioblastoma, and melanoma. Certain malignancies, such as prostate cancer, pleural mesothelioma, and colorectal carcinoma, exhibited minimal or absent CXCR4 expression on PET imaging. A correlation between in vivo PET uptake and histopathologic CXCR4 expression was evident in specific tumor types, though heterogeneity in receptor expression was reported. When compared to [18F]FDG PET/CT, [68Ga]Ga-Pentixafor PET/CT demonstrated lower lesion detectability, highlighting its potential as a theranostic tool for CXCR4-targeted therapies rather than a primary diagnostic modality. [68Ga]Ga-Pentixafor PET/CT represents a promising, yet evolving, tool in oncology. While its diagnostic performance may not rival that of [18F]FDG PET/CT across all tumor types, its theranostic potential underscores its value in the precision medicine landscape.