Abstract
Glomerular filtration rate (GFR) is a key indicator of renal function. Traditional methods for GFR measurement have limitations including invasiveness, low spatial resolution, and lengthy protocols. Positron emission tomography (PET) radiotracers have emerged as promising tools for non-invasive, accurate, and dynamic renal function assessment. Objectives: This systematic literature review evaluates the clinical utility, and current evidence surrounding PET radiotracers used for GFR measurement in humans, emphasizing advances over conventional renal imaging modalities. Methods: A systematic literature search was conducted in PubMed, Web of Science, and Scopus, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, from database inception to November 2024. The search identified studies evaluating PET-based measurement of glomerular filtration rate (GFR) and renal perfusion. Inclusion criteria encompassed human studies using PET radiotracers (e.g., (68)Ga, (18)F) with comparisons to reference standards (estimated GFR or serum creatinine). Two authors independently screened titles/abstracts, extracted data, and assessed bias using Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). Exclusions included animal studies, reviews, and non-English articles. Results: Eleven studies met inclusion criteria, with (68)Ga-EDTA showing the highest validation against reference standards such as (51)Cr-EDTA plasma clearance, demonstrating strong correlation. PET imaging offered superior spatial-temporal resolution, enabling accurate split renal function assessment and quantitative analysis of both filtration and perfusion. (68)Ga-somatostatin analogues exhibited moderate correlations between renal SUV and estimated GFR, with post-PRRT uptake changes indicating early nephrotoxicity. Among novel tracers, (68)Ga-FAPI showed a strong inverse SUV-GFR relationship, reflecting renal fibrosis and suggesting potential as a chronic kidney disease (CKD) biomarker but requires further clinical validation. Limitations across studies include small sample sizes, retrospective designs, and variability in reference standards. Conclusions: PET radiotracers, particularly (68)Ga-EDTA, represent a significant advancement for non-invasive, quantitative GFR measurement with improved precision and renal anatomical detail compared to traditional methods. Future prospective, large-scale human studies with standardized protocols are needed to establish these PET tracers as routine clinical tools in nephrology. Integration of hybrid PET/MRI and novel tracer development may further enhance renal diagnostic capabilities.