Retention kinetics of the 18F-labeled sympathetic nerve PET tracer LMI1195: Comparison with 11C-hydroxyephedrine and 123I-MIBG

Rudolf A. Werner, Christoph Rischpler, David Onthank, Constantin Lapa, Simon Robinson, Samuel Samnick, Mehrbod Javadi, Markus Schwaiger, Stephan G. Nekolla, Takahiro Higuchi

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

18F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine (18F-LMI1195) is a new PET tracer designed for noninvasive assessment of sympathetic innervation of the heart. The 18F label facilitates the imaging advantages of PET over SPECT technology while allowing centralized manufacturing. Highly specific neural uptake of 18F-LMI1195 has previously been established, but the retention kinetics are not yet fully understood. Methods: Healthy New Zealand White rabbits were studied with 18F-LMI1195 using a small-animal PET system. Dynamic 40-min chest scans were started just before intravenous bolus injection of 18F-LMI1195. Imaging was performed under norepinephrine transport inhibition with desipramine pretreatment, a 1.5 mg/kg desipramine chase administered 10 min after tracer injection, and saline treatment of controls. As a reference, cardiac uptake of 11C-hydroxyephedrine and 123I-metaiodobenzylguanidine (123I-MIBG) was examined by PET and planar scintigraphy, respectively. Results: Cardiac uptake of all 3 tracers was inhibited by pretreatment with desipramine. Stable cardiac tracer retention was delineated by dynamic PET in control rabbits for 11C-hydroxyephedrine (washout rate, 0.42% ± 0.57%/min) and 18F-LMI1195 (washout rate, 0.058% ± 0.28%/min). A desipramine chase increased 11C-hydroxyephedrine washout from the heart (2.43% ± 0.15%/min, P < 0.001), whereas 18F-LMI1195 washout was not influenced (0.059% ± 0.11%/min, not statistically significant). Additionally, a desipramine chase did not change the cardiac 123I-MIBG uptake (delayed heart-to-mediastinum ratio, 1.99 ± 0.12 (desipramine chase) vs. 2.05 ± 0.16 (controls), not statistically significant). Conclusion: In vivo norepinephrine transporter (NET) blockade with desipramine confirmed specific neural uptake of 18F-LMI1195, 11C-hydroxyephedrine, and 123I-MIBG in rabbit hearts. 11C-hydroxyephedrine cardiac retention was sensitive to a NET inhibitor chase, indicating a cycle of continuous NET uptake and release at the nerve terminals. In contrast, 18F-LMI1195 and 123IMIBG demonstrated stable storage at the nerve terminal with resistance to a NET inhibitor chase, mimicking physiologic norepinephrine turnover.

Original languageEnglish
Pages (from-to)1429-1433
Number of pages5
JournalJournal of Nuclear Medicine
Volume56
Issue number9
DOIs
Publication statusPublished - Sep 1 2015
Externally publishedYes

Fingerprint

Desipramine
Norepinephrine Plasma Membrane Transport Proteins
Rabbits
Norepinephrine
N-(3-bromo-4-(3-(18F)fluoro-propoxy)benzyl)guanidine
Mediastinum
Single-Photon Emission-Computed Tomography
Intravenous Injections
Radionuclide Imaging
Thorax
Technology
Injections

Keywords

  • C-hydroxyephedrine
  • Imetaiodobenzylguanidine
  • F-LMI1195
  • Positron emission tomography
  • Sympathetic nerve

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Retention kinetics of the 18F-labeled sympathetic nerve PET tracer LMI1195 : Comparison with 11C-hydroxyephedrine and 123I-MIBG. / Werner, Rudolf A.; Rischpler, Christoph; Onthank, David; Lapa, Constantin; Robinson, Simon; Samnick, Samuel; Javadi, Mehrbod; Schwaiger, Markus; Nekolla, Stephan G.; Higuchi, Takahiro.

In: Journal of Nuclear Medicine, Vol. 56, No. 9, 01.09.2015, p. 1429-1433.

Research output: Contribution to journalArticle

Werner, RA, Rischpler, C, Onthank, D, Lapa, C, Robinson, S, Samnick, S, Javadi, M, Schwaiger, M, Nekolla, SG & Higuchi, T 2015, 'Retention kinetics of the 18F-labeled sympathetic nerve PET tracer LMI1195: Comparison with 11C-hydroxyephedrine and 123I-MIBG', Journal of Nuclear Medicine, vol. 56, no. 9, pp. 1429-1433. https://doi.org/10.2967/jnumed.115.158493
Werner, Rudolf A. ; Rischpler, Christoph ; Onthank, David ; Lapa, Constantin ; Robinson, Simon ; Samnick, Samuel ; Javadi, Mehrbod ; Schwaiger, Markus ; Nekolla, Stephan G. ; Higuchi, Takahiro. / Retention kinetics of the 18F-labeled sympathetic nerve PET tracer LMI1195 : Comparison with 11C-hydroxyephedrine and 123I-MIBG. In: Journal of Nuclear Medicine. 2015 ; Vol. 56, No. 9. pp. 1429-1433.
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title = "Retention kinetics of the 18F-labeled sympathetic nerve PET tracer LMI1195: Comparison with 11C-hydroxyephedrine and 123I-MIBG",
abstract = "18F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine (18F-LMI1195) is a new PET tracer designed for noninvasive assessment of sympathetic innervation of the heart. The 18F label facilitates the imaging advantages of PET over SPECT technology while allowing centralized manufacturing. Highly specific neural uptake of 18F-LMI1195 has previously been established, but the retention kinetics are not yet fully understood. Methods: Healthy New Zealand White rabbits were studied with 18F-LMI1195 using a small-animal PET system. Dynamic 40-min chest scans were started just before intravenous bolus injection of 18F-LMI1195. Imaging was performed under norepinephrine transport inhibition with desipramine pretreatment, a 1.5 mg/kg desipramine chase administered 10 min after tracer injection, and saline treatment of controls. As a reference, cardiac uptake of 11C-hydroxyephedrine and 123I-metaiodobenzylguanidine (123I-MIBG) was examined by PET and planar scintigraphy, respectively. Results: Cardiac uptake of all 3 tracers was inhibited by pretreatment with desipramine. Stable cardiac tracer retention was delineated by dynamic PET in control rabbits for 11C-hydroxyephedrine (washout rate, 0.42{\%} ± 0.57{\%}/min) and 18F-LMI1195 (washout rate, 0.058{\%} ± 0.28{\%}/min). A desipramine chase increased 11C-hydroxyephedrine washout from the heart (2.43{\%} ± 0.15{\%}/min, P < 0.001), whereas 18F-LMI1195 washout was not influenced (0.059{\%} ± 0.11{\%}/min, not statistically significant). Additionally, a desipramine chase did not change the cardiac 123I-MIBG uptake (delayed heart-to-mediastinum ratio, 1.99 ± 0.12 (desipramine chase) vs. 2.05 ± 0.16 (controls), not statistically significant). Conclusion: In vivo norepinephrine transporter (NET) blockade with desipramine confirmed specific neural uptake of 18F-LMI1195, 11C-hydroxyephedrine, and 123I-MIBG in rabbit hearts. 11C-hydroxyephedrine cardiac retention was sensitive to a NET inhibitor chase, indicating a cycle of continuous NET uptake and release at the nerve terminals. In contrast, 18F-LMI1195 and 123IMIBG demonstrated stable storage at the nerve terminal with resistance to a NET inhibitor chase, mimicking physiologic norepinephrine turnover.",
keywords = "C-hydroxyephedrine, Imetaiodobenzylguanidine, F-LMI1195, Positron emission tomography, Sympathetic nerve",
author = "Werner, {Rudolf A.} and Christoph Rischpler and David Onthank and Constantin Lapa and Simon Robinson and Samuel Samnick and Mehrbod Javadi and Markus Schwaiger and Nekolla, {Stephan G.} and Takahiro Higuchi",
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TY - JOUR

T1 - Retention kinetics of the 18F-labeled sympathetic nerve PET tracer LMI1195

T2 - Comparison with 11C-hydroxyephedrine and 123I-MIBG

AU - Werner, Rudolf A.

AU - Rischpler, Christoph

AU - Onthank, David

AU - Lapa, Constantin

AU - Robinson, Simon

AU - Samnick, Samuel

AU - Javadi, Mehrbod

AU - Schwaiger, Markus

AU - Nekolla, Stephan G.

AU - Higuchi, Takahiro

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 18F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine (18F-LMI1195) is a new PET tracer designed for noninvasive assessment of sympathetic innervation of the heart. The 18F label facilitates the imaging advantages of PET over SPECT technology while allowing centralized manufacturing. Highly specific neural uptake of 18F-LMI1195 has previously been established, but the retention kinetics are not yet fully understood. Methods: Healthy New Zealand White rabbits were studied with 18F-LMI1195 using a small-animal PET system. Dynamic 40-min chest scans were started just before intravenous bolus injection of 18F-LMI1195. Imaging was performed under norepinephrine transport inhibition with desipramine pretreatment, a 1.5 mg/kg desipramine chase administered 10 min after tracer injection, and saline treatment of controls. As a reference, cardiac uptake of 11C-hydroxyephedrine and 123I-metaiodobenzylguanidine (123I-MIBG) was examined by PET and planar scintigraphy, respectively. Results: Cardiac uptake of all 3 tracers was inhibited by pretreatment with desipramine. Stable cardiac tracer retention was delineated by dynamic PET in control rabbits for 11C-hydroxyephedrine (washout rate, 0.42% ± 0.57%/min) and 18F-LMI1195 (washout rate, 0.058% ± 0.28%/min). A desipramine chase increased 11C-hydroxyephedrine washout from the heart (2.43% ± 0.15%/min, P < 0.001), whereas 18F-LMI1195 washout was not influenced (0.059% ± 0.11%/min, not statistically significant). Additionally, a desipramine chase did not change the cardiac 123I-MIBG uptake (delayed heart-to-mediastinum ratio, 1.99 ± 0.12 (desipramine chase) vs. 2.05 ± 0.16 (controls), not statistically significant). Conclusion: In vivo norepinephrine transporter (NET) blockade with desipramine confirmed specific neural uptake of 18F-LMI1195, 11C-hydroxyephedrine, and 123I-MIBG in rabbit hearts. 11C-hydroxyephedrine cardiac retention was sensitive to a NET inhibitor chase, indicating a cycle of continuous NET uptake and release at the nerve terminals. In contrast, 18F-LMI1195 and 123IMIBG demonstrated stable storage at the nerve terminal with resistance to a NET inhibitor chase, mimicking physiologic norepinephrine turnover.

AB - 18F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine (18F-LMI1195) is a new PET tracer designed for noninvasive assessment of sympathetic innervation of the heart. The 18F label facilitates the imaging advantages of PET over SPECT technology while allowing centralized manufacturing. Highly specific neural uptake of 18F-LMI1195 has previously been established, but the retention kinetics are not yet fully understood. Methods: Healthy New Zealand White rabbits were studied with 18F-LMI1195 using a small-animal PET system. Dynamic 40-min chest scans were started just before intravenous bolus injection of 18F-LMI1195. Imaging was performed under norepinephrine transport inhibition with desipramine pretreatment, a 1.5 mg/kg desipramine chase administered 10 min after tracer injection, and saline treatment of controls. As a reference, cardiac uptake of 11C-hydroxyephedrine and 123I-metaiodobenzylguanidine (123I-MIBG) was examined by PET and planar scintigraphy, respectively. Results: Cardiac uptake of all 3 tracers was inhibited by pretreatment with desipramine. Stable cardiac tracer retention was delineated by dynamic PET in control rabbits for 11C-hydroxyephedrine (washout rate, 0.42% ± 0.57%/min) and 18F-LMI1195 (washout rate, 0.058% ± 0.28%/min). A desipramine chase increased 11C-hydroxyephedrine washout from the heart (2.43% ± 0.15%/min, P < 0.001), whereas 18F-LMI1195 washout was not influenced (0.059% ± 0.11%/min, not statistically significant). Additionally, a desipramine chase did not change the cardiac 123I-MIBG uptake (delayed heart-to-mediastinum ratio, 1.99 ± 0.12 (desipramine chase) vs. 2.05 ± 0.16 (controls), not statistically significant). Conclusion: In vivo norepinephrine transporter (NET) blockade with desipramine confirmed specific neural uptake of 18F-LMI1195, 11C-hydroxyephedrine, and 123I-MIBG in rabbit hearts. 11C-hydroxyephedrine cardiac retention was sensitive to a NET inhibitor chase, indicating a cycle of continuous NET uptake and release at the nerve terminals. In contrast, 18F-LMI1195 and 123IMIBG demonstrated stable storage at the nerve terminal with resistance to a NET inhibitor chase, mimicking physiologic norepinephrine turnover.

KW - C-hydroxyephedrine

KW - Imetaiodobenzylguanidine

KW - F-LMI1195

KW - Positron emission tomography

KW - Sympathetic nerve

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