Preclinical Evaluation and Preliminary Clinical Study of Al18F-NOTA for PET/CT Imaging of Renal Function

Abstract

Accurate renal function assessment is crucial for kidney disease diagnosis and management, yet current methods lack real-time, quantitative in vivo evaluation. Capitalizing on the superior sensitivity and quantitative capabilities of fluorine-18 PET, we developed ¹⁸F-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid (Al¹⁸F-NOTA) for the assessment of renal function. It was successfully radiosynthesized with high radiolabeling and low plasma protein binding. In healthy mice, Al¹⁸F-NOTA showed rapid renal clearance. In three distinct preclinical AKI models, PET imaging revealed significantly increased tracer accumulation in the injured kidneys and reduced GFR, which was validated by clinical laboratory techniques. A preliminary clinical study demonstrated rapid renal uptake and urinary excretion in healthy volunteers, whereas patients with renal dysfunction showed delayed clearance and increased renal retention. PET-derived renograms and GFR values were also consistent with clinical assessments, with no adverse effects observed. These findings establish Al¹⁸F-NOTA PET imaging as a highly promising, noninvasive diagnostic tool for assessing renal function.