Functional Renal Imaging with 2-Deoxy-2-¹⁸F-Fluorosorbitol PET in Rat Models of Renal Disorders

Abstract

Precise regional quantitative assessment of renal function is limited with conventional Tc-labeled renal radiotracers. A recent study reported that the PET radiotracer 2-deoxy-2-F-fluorosorbitol (F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, F-FDS is available via simple reduction from routinely usedF-FDG. We aimed to further investigate the potential of F-FDS PET as a functional renal imaging agent using rat models of kidney disease. Two different rat models of renal impairment were investigated: induction of acute renal failure by intramuscular administration of glycerol in the hind legs, and induction of unilateral ureteral obstruction by ligation of the left ureter. At 24 h after these procedures, dynamic 30-min F-FDS PET data were acquired using a dedicated small-animal PET system. UrineF-FDS radioactivity 30 min after radiotracer injection was measured together with coinjected Tc-diethylenetriaminepentaacetic acid urine activity. Dynamic PET imaging demonstrated rapid F-FDS accumulation in the renal cortex and rapid radiotracer excretion via the kidneys in healthy control rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in acute renal failure rats and unilateral ureteral obstruction kidneys. Measured urine radiotracer concentrations ofF-FDS and Tc-diethylenetriaminepentaacetic acid correlated well with each other ( = 0.84, < 0.05). F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases.F-FDS PET imaging, with its advantages of high spatiotemporal resolution and simple tracer production, could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging.

Role of 18F-fluorodeoxyglucose (FDG) and 18F-2-fluorodeoxy sorbitol (FDS) in autoimmune hypophysitis: a case report

“…FDS can be synthesized through a three-step automated reaction from 18 F ions or reduced from FDG with NaBH 4 [9,11] and shares a similar structure with FDG. FDS can be rapidly eliminated from organs and blood through the renal-urinary system [9], and due to its favorable renal kinetics, it is also considered a potential tracer for renal functional imaging [21]. Previously, FDS was reported to be absorbed by Enterobacteriaceae, leading to its use as a promising tracer for bacterial infection [9][10][11].…”

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“…by obstruction) prior to PRRT 69. Therefore, [ 68 Ga]-EDTA or the recently introduced renal PET agent 2-deoxy-2- 18 F-fluorosorbitol ([ 18 F]-FDS), which can be produced by a simple one-step reduction from [ 18 F]-FDG, may overcome the hurdles of conventional renal scintigraphy 69-71 and be useful tools in the management of PRRT patients 70.…”

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“… 18 F has a relatively long physical half-life of 110 min, which allows for the use of delivery systems [ 22 ] and such an approach has already been proven to be cost-effective for 2-deoxy-2- 18 F-fluoro- d -glucose ( 18 F-FDG) [ 23 ]; 18 F has the shortest positron range in tissue compared to other established MPI PET radionuclides [ 19 ], and, thus, it may have the highest spatial resolution [ 17 ]; the lower positron energy with higher positron yield allows for injection of a considerably lower amount of radioactivity [ 13 ]; its long half-life opens the door for delayed imaging protocols (e.g. for assessment of blood flow alterations at late scan time-points) [ 24 ]; due to the short half-life of currently used PET MPI agents, stress imaging is only feasible while placing the patient under pharmacological stress.…”

“…the lower positron energy with higher positron yield allows for injection of a considerably lower amount of radioactivity [ 13 ];…”

“…In this light, several studies have already reported on the superior imaging characteristics and higher accuracy of PET MPI compared to conventional SPECT MPI [ 11 , 12 ]. Moreover, PET includes attenuation correction on a routine basis, as hybrid systems equipped with computed tomography (CT) are routinely installed, which also allows for anatomic co-registration [ 13 ]. Apart from that, with traditional PET agents, both rest and stress images can be acquired during one single study, mainly due to the shorter half-life of PET agents [ 14 ] and PET has also opened the door for reliable quantification of absolute myocardial blood flow (MBF) [ 15 , 16 ].…”