Initial preclinical evaluation of 18F-fluorodeoxysorbitol PET as a novel functional renal imaging agent

Hiroshi Wakabayashi, Rudolf A. Werner, Nobuyuki Hayakawa, Mehrbod S. Javadi, Chen Xinyu, Ken Herrmann, Steven P. Rowe, Constantin Lapa, Takahiro Higuchi

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Accurate assessment of kidney function plays an essential role for optimal clinical decision making in a variety of diseases. The major intrinsic advantages of PET are superior spatial and temporal resolutions for quantitative tomographic renal imaging. 2-deoxy-2-18F-fluorodeoxysorbitol (18F-FDS) is an analog of sorbitol that is reported to be freely filtered at the renal glomerulus without reabsorption at the tubule. Furthermore, it can be synthesized via simple reduction of widely available 18F-FDG. We tested the feasibility of 18F-FDS renal PET imaging in rats. Methods: The systemic and renal distribution of 18F-FDS were determined by dynamic 35-min PET imaging (15 frames x 8 s, 26 frames x 30 s, 20 frames x 60 s) with a dedicated small-animal PET system and postmortem tissue counting in healthy rats. Distribution of coinjected 99mTc-diethylenetriaminepentaacetic acid (DTPA) was also estimated as a reference. Plasma binding and in vivo stability of 18F-FDS were determined. Results: In vivo PET imaging visualized rapid excretion of the administrated 18F-FDS from both kidneys, with minimal tracer accumulation in other organs. Initial cortical tracer uptake followed by visualization of the collecting system could be observed with high contrast. Split-function renography curves were successfully obtained in healthy rats (the time of maximal concentration [Tmax] right [R] = 2.8 ± 1.2 min, Tmax left [L] = 2.9 ± 1.5 min, the time of half maximal concentration [T1/2max] R = 8.8 ± 3.7 min, T1/2max L = 11.1 ± 4.9 min). Postmortem tissue counting of 18F-FDS confirmed the high kidney extraction (kidney activities at 10, 30, and 60 min after tracer injection [percentage injected dose per gram]: 1.8 ± 0.7, 1.2 ± 0.1, and 0.5 ± 0.2, respectively) in a degree comparable to 99mTc-DTPA (2.5 ± 1.0, 1.5 ± 0.2, and 0.8 ± 0.3, respectively). Plasma protein binding of 18F-FDS was low (<0.1%), and metabolic transformation was not detected in serum and urine. Conclusion: In rat experiments, 18F-FDS demonstrated high kidney extraction and excretion, low plasma protein binding, and high metabolic stability as preferable properties for renal imaging. These preliminary results warrant further confirmatory studies in large animal models and clinical studies as a novel functional renal imaging agent, given the advantages of PET technology and broad tracer availability.

Original languageEnglish
Pages (from-to)1625-1628
Number of pages4
JournalJournal of Nuclear Medicine
Volume57
Issue number10
DOIs
Publication statusPublished - Oct 1 2016
Externally publishedYes

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Renal Agents
Kidney
Protein Binding
Blood Proteins
Radioisotope Renography
Acids
Sorbitol
Fluorodeoxyglucose F18

Keywords

  • F-FDS
  • Tc-DTPA
  • PET
  • Rat
  • Renography

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Initial preclinical evaluation of 18F-fluorodeoxysorbitol PET as a novel functional renal imaging agent. / Wakabayashi, Hiroshi; Werner, Rudolf A.; Hayakawa, Nobuyuki; Javadi, Mehrbod S.; Xinyu, Chen; Herrmann, Ken; Rowe, Steven P.; Lapa, Constantin; Higuchi, Takahiro.

In: Journal of Nuclear Medicine, Vol. 57, No. 10, 01.10.2016, p. 1625-1628.

Research output: Contribution to journalArticle

Wakabayashi, H, Werner, RA, Hayakawa, N, Javadi, MS, Xinyu, C, Herrmann, K, Rowe, SP, Lapa, C & Higuchi, T 2016, 'Initial preclinical evaluation of 18F-fluorodeoxysorbitol PET as a novel functional renal imaging agent', Journal of Nuclear Medicine, vol. 57, no. 10, pp. 1625-1628. https://doi.org/10.2967/jnumed.116.172718
Wakabayashi, Hiroshi ; Werner, Rudolf A. ; Hayakawa, Nobuyuki ; Javadi, Mehrbod S. ; Xinyu, Chen ; Herrmann, Ken ; Rowe, Steven P. ; Lapa, Constantin ; Higuchi, Takahiro. / Initial preclinical evaluation of 18F-fluorodeoxysorbitol PET as a novel functional renal imaging agent. In: Journal of Nuclear Medicine. 2016 ; Vol. 57, No. 10. pp. 1625-1628.
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title = "Initial preclinical evaluation of 18F-fluorodeoxysorbitol PET as a novel functional renal imaging agent",
abstract = "Accurate assessment of kidney function plays an essential role for optimal clinical decision making in a variety of diseases. The major intrinsic advantages of PET are superior spatial and temporal resolutions for quantitative tomographic renal imaging. 2-deoxy-2-18F-fluorodeoxysorbitol (18F-FDS) is an analog of sorbitol that is reported to be freely filtered at the renal glomerulus without reabsorption at the tubule. Furthermore, it can be synthesized via simple reduction of widely available 18F-FDG. We tested the feasibility of 18F-FDS renal PET imaging in rats. Methods: The systemic and renal distribution of 18F-FDS were determined by dynamic 35-min PET imaging (15 frames x 8 s, 26 frames x 30 s, 20 frames x 60 s) with a dedicated small-animal PET system and postmortem tissue counting in healthy rats. Distribution of coinjected 99mTc-diethylenetriaminepentaacetic acid (DTPA) was also estimated as a reference. Plasma binding and in vivo stability of 18F-FDS were determined. Results: In vivo PET imaging visualized rapid excretion of the administrated 18F-FDS from both kidneys, with minimal tracer accumulation in other organs. Initial cortical tracer uptake followed by visualization of the collecting system could be observed with high contrast. Split-function renography curves were successfully obtained in healthy rats (the time of maximal concentration [Tmax] right [R] = 2.8 ± 1.2 min, Tmax left [L] = 2.9 ± 1.5 min, the time of half maximal concentration [T1/2max] R = 8.8 ± 3.7 min, T1/2max L = 11.1 ± 4.9 min). Postmortem tissue counting of 18F-FDS confirmed the high kidney extraction (kidney activities at 10, 30, and 60 min after tracer injection [percentage injected dose per gram]: 1.8 ± 0.7, 1.2 ± 0.1, and 0.5 ± 0.2, respectively) in a degree comparable to 99mTc-DTPA (2.5 ± 1.0, 1.5 ± 0.2, and 0.8 ± 0.3, respectively). Plasma protein binding of 18F-FDS was low (<0.1{\%}), and metabolic transformation was not detected in serum and urine. Conclusion: In rat experiments, 18F-FDS demonstrated high kidney extraction and excretion, low plasma protein binding, and high metabolic stability as preferable properties for renal imaging. These preliminary results warrant further confirmatory studies in large animal models and clinical studies as a novel functional renal imaging agent, given the advantages of PET technology and broad tracer availability.",
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author = "Hiroshi Wakabayashi and Werner, {Rudolf A.} and Nobuyuki Hayakawa and Javadi, {Mehrbod S.} and Chen Xinyu and Ken Herrmann and Rowe, {Steven P.} and Constantin Lapa and Takahiro Higuchi",
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AU - Werner, Rudolf A.

AU - Hayakawa, Nobuyuki

AU - Javadi, Mehrbod S.

AU - Xinyu, Chen

AU - Herrmann, Ken

AU - Rowe, Steven P.

AU - Lapa, Constantin

AU - Higuchi, Takahiro

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N2 - Accurate assessment of kidney function plays an essential role for optimal clinical decision making in a variety of diseases. The major intrinsic advantages of PET are superior spatial and temporal resolutions for quantitative tomographic renal imaging. 2-deoxy-2-18F-fluorodeoxysorbitol (18F-FDS) is an analog of sorbitol that is reported to be freely filtered at the renal glomerulus without reabsorption at the tubule. Furthermore, it can be synthesized via simple reduction of widely available 18F-FDG. We tested the feasibility of 18F-FDS renal PET imaging in rats. Methods: The systemic and renal distribution of 18F-FDS were determined by dynamic 35-min PET imaging (15 frames x 8 s, 26 frames x 30 s, 20 frames x 60 s) with a dedicated small-animal PET system and postmortem tissue counting in healthy rats. Distribution of coinjected 99mTc-diethylenetriaminepentaacetic acid (DTPA) was also estimated as a reference. Plasma binding and in vivo stability of 18F-FDS were determined. Results: In vivo PET imaging visualized rapid excretion of the administrated 18F-FDS from both kidneys, with minimal tracer accumulation in other organs. Initial cortical tracer uptake followed by visualization of the collecting system could be observed with high contrast. Split-function renography curves were successfully obtained in healthy rats (the time of maximal concentration [Tmax] right [R] = 2.8 ± 1.2 min, Tmax left [L] = 2.9 ± 1.5 min, the time of half maximal concentration [T1/2max] R = 8.8 ± 3.7 min, T1/2max L = 11.1 ± 4.9 min). Postmortem tissue counting of 18F-FDS confirmed the high kidney extraction (kidney activities at 10, 30, and 60 min after tracer injection [percentage injected dose per gram]: 1.8 ± 0.7, 1.2 ± 0.1, and 0.5 ± 0.2, respectively) in a degree comparable to 99mTc-DTPA (2.5 ± 1.0, 1.5 ± 0.2, and 0.8 ± 0.3, respectively). Plasma protein binding of 18F-FDS was low (<0.1%), and metabolic transformation was not detected in serum and urine. Conclusion: In rat experiments, 18F-FDS demonstrated high kidney extraction and excretion, low plasma protein binding, and high metabolic stability as preferable properties for renal imaging. These preliminary results warrant further confirmatory studies in large animal models and clinical studies as a novel functional renal imaging agent, given the advantages of PET technology and broad tracer availability.

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KW - Tc-DTPA

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