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Purpose: The production of 51 Cr-labelled ethylenediaminetetraacetic acid ( 51 Cr-EDTA), a validated and widely used radio-isotopic tracer for glomerular filtration rate (GFR) measurement in Europe, was recently halted by the manufacturer. Technetium-99m-diethylenetriaminepentaacetic acid ( 99m Tc-DTPA) clearance has so far mostly been restricted to assessment of separate renal function by scintigraphy, but scarcely used and validated for GFR measurement. We compared the performances of 51 Cr-EDTA and 99m Tc-DTPA for GFR and extracellular fluid measurement., Methods: In a multi-centre prospective study, 51 Cr-EDTA and 99m Tc-DTPA were simultaneously injected into 88 patients, and their urinary and plasma clearances, as well as their volumes of distribution, were measured during seven 30-min periods after a 90-min equilibrium time., Results: Mean age was 52.2 ± 14.5 years, 59% were men. Urinary clearances of 51 Cr-EDTA and 99m Tc-DTPA were 64.1 ± 27.6 and 66.1 ± 28.0 mL/min, respectively, with a mean bias of 2.00 ± 2.25 mL/min, an accuracy within 10% of 95% [95% CI 91-99], and a coefficient of determination (R 2 ) of 0.994. Plasma clearances of 51 Cr-EDTA and 99m Tc-DTPA were 66.1 ± 25.8 and 68.1 ± 26.6 mL/min, respectively, with a mean bias of 1.96 ± 3.32 mL/min, an accuracy within 10% of 91% [95% CI 85-97] and a R 2 of 0.985. Distribution volumes were 17.3 ± 4.6 L for 51 Cr-EDTA and 16.6 ± 4.6 L for 99m Tc-DTPA (R 2 0.930)., Conclusion: The accuracy and precision of 99m Tc-DTPA clearance, compared to 51 Cr-EDTA clearance, was excellent for both urinary and plasma clearance methods, despite an approximate 2 mL/min overestimation, showing that the tracer is a reliable alternative to 51 Cr-EDTA for GFR measurement.