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J Nucl Med. 2015 Sep;56(9):1429-33. doi: 10.2967/jnumed.115.158493. Epub 2015 Jul 16.

Retention Kinetics of the 18F-Labeled Sympathetic Nerve PET Tracer LMI1195: Comparison with 11C-Hydroxyephedrine and 123I-MIBG.

Author information

1
Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany Comprehensive Heart Failure Center (CHFC), University of Wuerzburg, Wuerzburg, Germany.
2
Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany.
3
Lantheus Medical Imaging, North Billerica, Massachusetts.
4
Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany.
5
Division of Nuclear Medicine, Russell H. Morgan Department of Radiology, Johns Hopkins University, Baltimore, Maryland; and.
6
Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
7
Department of Nuclear Medicine, University of Wuerzburg, Wuerzburg, Germany Comprehensive Heart Failure Center (CHFC), University of Wuerzburg, Wuerzburg, Germany thiguchi@me.com.

Abstract

(18)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine ((18)F-LMI1195) is a new PET tracer designed for noninvasive assessment of sympathetic innervation of the heart. The (18)F label facilitates the imaging advantages of PET over SPECT technology while allowing centralized manufacturing. Highly specific neural uptake of (18)F-LMI1195 has previously been established, but the retention kinetics are not yet fully understood.

METHODS:

Healthy New Zealand White rabbits were studied with (18)F-LMI1195 using a small-animal PET system. Dynamic 40-min chest scans were started just before intravenous bolus injection of (18)F-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 (11)C-hydroxyephedrine and (123)I-metaiodobenzylguanidine ((123)I-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 (11)C-hydroxyephedrine (washout rate, 0.42% ± 0.57%/min) and (18)F-LMI1195 (washout rate, 0.058% ± 0.28%/min). A desipramine chase increased (11)C-hydroxyephedrine washout from the heart (2.43% ± 0.15%/min, P < 0.001), whereas (18)F-LMI1195 washout was not influenced (0.059% ± 0.11%/min, not statistically significant). Additionally, a desipramine chase did not change the cardiac (123)I-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 (18)F-LMI1195, (11)C-hydroxyephedrine, and (123)I-MIBG in rabbit hearts. (11)C-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, (18)F-LMI1195 and (123)I-MIBG demonstrated stable storage at the nerve terminal with resistance to a NET inhibitor chase, mimicking physiologic norepinephrine turnover.

KEYWORDS:

11C-hydroxyephedrine; 123I-metaiodobenzylguanidine; 18F-LMI1195; positron emission tomography; sympathetic nerve

PMID:
26182969
DOI:
10.2967/jnumed.115.158493
[Indexed for MEDLINE]
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