RT Journal Article
SR Electronic
T1 Retention Kinetics of the <sup>18</sup>F-Labeled Sympathetic Nerve PET Tracer LMI1195: Comparison with <sup>11</sup>C-Hydroxyephedrine and <sup>123</sup>I-MIBG
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1429
OP 1433
DO 10.2967/jnumed.115.158493
VO 56
IS 9
A1 Rudolf A. Werner
A1 Christoph Rischpler
A1 David Onthank
A1 Constantin Lapa
A1 Simon Robinson
A1 Samuel Samnick
A1 Mehrbod Javadi
A1 Markus Schwaiger
A1 Stephan G. Nekolla
A1 Takahiro Higuchi
YR 2015
UL http://jnm.snmjournals.org/content/56/9/1429.abstract
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 &lt; 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 123I-MIBG demonstrated stable storage at the nerve terminal with resistance to a NET inhibitor chase, mimicking physiologic norepinephrine turnover.