⁶⁸Ga-EDTA PET/CT Imaging and Plasma Clearance for Glomerular Filtration Rate Quantification: Comparison to Conventional ⁵¹Cr-EDTA

Abstract

Glomerular filtration rate (GFR) can accurately be determined using 51 Cr-ethylenediaminetetraacetic acid (EDTA) plasma clearance counting but is time-consuming and requires technical skills and equipment not always available in imaging departments. 68 Ga-EDTA can be readily available using an onsite generator, and PET/CT enables both imaging of renal function and accurate camera-based quantitation of clearance of activity from blood and its appearance in the urine. This study aimed to assess agreement between 68 Ga-EDTA GFR ( 68 Ga-GFR) and 51 Cr-EDTA GFR ( 51 Cr-GFR), using serial plasma sampling and PET imaging. Methods: 68 Ga-EDTA and 51 Cr-EDTA were injected concurrently in 31 patients. Dynamic PET/CT encompassing the kidneys was acquired for 10 min followed by 3 sequential 3-min multibed step acquisitions from kidneys to bladder. PET quantification was performed using renal activity at 1-2 min (PET initial ), renal excretion at 2-10 min (PET early ), and, subsequently, urinary excretion into the collecting system and bladder (PET late ). Plasma sampling at 2, 3, and 4 h was performed, with 68 Ga followed by 51 Cr counting after positron decay. The level of agreement for GFR determination was calculated using a Bland-Altman plot and Pearson correlation coefficient (PCC). Results: 51 Cr-GFR ranged from 10 to 220 mL/min (mean, 85 mL/min). There was good agreement between 68 Ga-GFR and 51 Cr-GFR using serial plasma sampling, with a BlandAltman bias of −14 ± 20 mL/min and a PCC of 0.94 (95% confidence interval, 0.88-0.97). Of the 3 methods used for camera-based quantification, the strongest correlation was for plasma sampling-derived GFR with PET late (PCC of 0.90; 95% confidence interval,. Conclusion: 68 Ga-GFR agreed well with 51 Cr-GFR for estimation of GFR using serial plasma counting. PET dynamic imaging provides a method to estimate GFR without plasma sampling, with the additional advantage of enabling renal imaging in a single study. Additional validation in a larger cohort is warranted to further assess utility.

A PET Tracer for Renal Organic Cation Transporters, 11C-Metformin: Radiosynthesis and Preclinical Proof-of-Concept Studies

“…Thirty minutes after reincubation of LLC-PK 1 proximal tubule cells previously exposed to 11 C-metformin, 40% of the accumulated dose was lost, showing that 11 C-metformin is not trapped in the cells. This finding is consistent with previous observations from studies examining the kinetics of cold metformin, which demonstrated that more than 90% of the absorbed dose is eliminated by the kidneys (8,9). Moreover, the autoradiography studies provided evidence that there is a high cortical uptake with rapid concomitant elimination and accumulation of 11 Cmetformin in the medullary parts, supporting the view that there is a high renal extraction of 11 C-metformin.…”

“…Recently in The Journal of Nuclear Medicine, PET/CT was used in conjunction with 68 Ga-ethylenediaminetetraacetic acid (EDTA) to measure the glomerular filtration rate (8), suggesting that PET/CT is a suitable methodology to also study the renal and hepatic handling of cationic drugs, but so far no specific cation tracer has emerged for renal PET studies. The ideal tracer has high affinity and is specific for the OCT2 transporter, has negligible metabolism and plasma protein binding with a high first-pass renal extraction, and is excreted in high concentrations in the urine.…”

Initial Preclinical Evaluation of 18F-Fluorodeoxysorbitol PET as a Novel Functional Renal Imaging Agent

“…One of the most promising tracers is 68 Ga-EDTA, which was recently introduced for renal PET imaging (19,20). In a clinical study comprising 31 patients, Hofman et al (20) confirmed good agreement of GFR estimation with 68 Ga-EDTA PET and 51 Cr-EDTA plasma clearance. A disadvantage of 68 Ga-labeled tracers is the requirement of costly on-site generators, although the availability of 68 Ga is currently improving because of the increased use for somatostatin receptor PET imaging.…”

“…Therefore, several PET tracers have been developed as potential candidates for quantitative renal imaging including 68 Ga-and 18 F-labeled compounds (16)(17)(18). One of the most promising tracers is 68 Ga-EDTA, which was recently introduced for renal PET imaging (19,20). In a clinical study comprising 31 patients, Hofman et al (20) confirmed good agreement of GFR estimation with 68 Ga-EDTA PET and 51 Cr-EDTA plasma clearance.…”

Back to the Future: Nuclear Medicine Rediscovers Its Therapeutic Roots

“…However, there is a range of other agents that could rapidly enter into routine nuclear medicine practice. These include agents for renal scanning [22] and ventilationperfusion imaging [23]. Table 21.2 provides a list of Ga-68-labelled agents that are used clinically in my department.…”