Novel functional renal PET imaging with ¹⁸F-FDS in human subjects

Abstract

The novel PET probe 2-deoxy-2-¹⁸F-fluoro-D-sorbitol (¹⁸F-FDS) has demonstrated favorable renal kinetics in animals. We aimed to elucidate its imaging properties in two human volunteers. ¹⁸F-FDS was produced by a simple one-step reduction from ¹⁸F-FDG. On dynamic renal PET, the cortex was delineated and activity gradually transited in the parenchyma, followed by radiotracer excretion. No adverse effects were reported. Given the higher spatiotemporal resolution of PET relative to conventional scintigraphy, ¹⁸F-FDS PET offers a more thorough evaluation of human renal kinetics. Due to its simple production from ¹⁸F-FDG, ¹⁸F-FDS is virtually available at any PET facility with radiochemistry infrastructure.

FIGURE.

Due to its underlying sorbitol structure that shares kinetic properties to the gold standard inulin (sorbitol-to-inulin clearance ratio = 1.01) ¹, the novel renal PET imaging agent 2-deoxy-2-¹⁸F-fluoro-D-sorbitol (¹⁸F-FDS) demonstrated promising properties for renal imaging in preclinical experiments ^{2, 3}. Furthermore, ¹⁸F-FDS can be easily produced by a simple one-step reduction of 2-deoxy-2-¹⁸F-fluoro-D-glucose (¹⁸F-FDG) ^{4, 5}. We aimed to elucidate its imaging properties in human. ¹⁸F-FDS was produced by a simple one-step reduction from ¹⁸F-FDG (A). Two volunteers underwent dynamic ¹⁸F-FDS PET/CT and standard and blood urine tests were normal at the time of the scan (serum creatinine: <1.2 mg/dl, estimated GFR: >60 mL/min/1.73m²). Volumes of interest (VOIs, outer layer covering the renal cortex and middle/inner layer covering the renal medulla) were placed on the left and right kidneys. B-D displays the right kidney of a 48-year old female volunteer. After rapid clearance of the circulation system, the radiotracer was excreted through the urinary system and finally transited into the collecting systems: In a dynamic PET acquisition centered on the kidneys, only the renal cortex was delineated 60 seconds after injection of the radiotracer, reflecting blood flow (B). Thereafter, activity gradually accumulated in the renal parenchyma and reached the pelvicalyceal system after 210 seconds (C), followed by radiotracer excretion. Finally, retention in the kidneys diminished completely. Three-dimensional VOIs placed on the outer (cortical) and middle/inner (medullary) layers of the kidneys confirmed ¹⁸F-FDS transit from the renal cortex through the medulla towards the pelvis (D). For the second volunteer, similar results on renal PET imaging were recorded. Given the higher spatiotemporal resolution of PET technologies relative to conventional 2D scintigraphy, ¹⁸F-FDS PET may offer a more thorough evaluation of human renal kinetics. Notably, ¹⁸F-FDS can be easily produced from the most commonly used PET radiotracer ¹⁸F-FDG, providing access for virtually any PET facility with radiochemistry infrastructure. Moreover, due to the long half-life (109.4 min), delivery from central cyclotron facilities to smaller hospitals can be envisaged ⁶, which has been proven to be cost-effective for oncology imaging with ¹⁸F-FDG ⁷. ¹⁸F-FDS PET has the major advantage of lower positron energy along with higher positron yield, and therefore, the increased count rates offer the opportunity to inject a considerably lower amount of activity. Hence, ¹⁸F-FDS PET could significantly lower radiation exposure to children without sacrificing imaging quality ⁸. Thus, ¹⁸F-FDS could also be applied to pediatric indications, e.g. to identify structural abnormalities with significant functional obstruction ⁹.