[en] The autonomic nervous system plays a critical role in the regulation of cardiac function. Abnormalities of cardiac innervation have been implicated in the pathophysiology of many heart diseases, including sudden cardiac death and congestive heart failure. In an effort to provide clinicians with the ability to regionally map cardiac innervation, several radiotracers for imaging cardiac sympathetic neurons have been developed. This paper reviews the development of neuronal imaging agents and discusses their emerging role in the noninvasive assessment of cardiac sympathetic innervation

[en] The antidepressant desipramine (DMI) and its principal metabolite 2-hydroxydesipramine (HDMI) have been radiolabeled with ¹¹C for PET studies. The normethyl precursors of DMI and HDMI were synthesized from iminodibenzyl in 35% and 11% overall yield, respectively. Direct methylation of the normethyl precursor with [¹¹C]CH₃I, followed by HPLC purification, provided [¹¹C]DMI and [¹¹]HDMI in 18-30% and 15-23% decay-corrected radiochemical yields, respectively, in a 45 min synthesis time from end of bombardment. The specific activities of the two radiotracers were >1459 Ci/mmol at the end of synthesis. [¹¹C]DMI and [¹¹C]HDMI have potential utility as PET radiotracers for the norepinephrine transporter

[en] The in vivo behavior of (-)-[¹¹C]phenylephrine (PHEN) is compared with the structurally similar but monoamine oxidase (MAO)-resistant analog (-)-[¹¹C]-m-hydroxyephedrine (HED), which is an established heart neuronal marker. The chiral synthesis of PHEN has been achieved by direct methylation of (-)-m-octopamine with either ¹¹CH₃I or CF₃SO¹¹₃CH₃. These synthetic methods produced PHEN with a specific activity ranging from 500-1000 Ci/mmol, in a radiochemical yield of >50% (EOS) and with an enantiomeric purity of 94-96%. Biodistribution studies indicate the initial uptake of PHEN in rat heart is approximately half that of HED. Following PHEN injection, radioactivity egresses from the rat heart rapidly, with 50% washout occurring from 5 to 60 min. HED washout over this interval was less than 20%. The heart neuronal selectivity determined by desipramine blockade of the amine neuronal transporter was 75-77% compared to 92-95% for HED. Ring-labeled (-)-[³H]phenylephrine gave tissue-to-blood concentration ratios and heart clearance times very similar to PHEN. Rats pretreated with the MAO A inhibitor clorgyline showed higher levels of activity in the heart at 15 and 60 min. Tandem PET studies with PHEN and HED in the closed-chest dog provided excellent heart images with both tracers

[en] An iodinated analog of PK11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxamide, a specific antagonist of the peripheral-type benzodiazepine receptor (ω₃), has been synthesized in three steps with an overall chemical yield of 40%. Both [¹²³I]- and [¹²⁵I]-Iodo-PK11195 have been synthesized by solid-state isotopic exchange in >60% isolated radiochemical yield and specific activity of 233-348 mCi/mmol. Tissue distribution studies in rats indicate a high uptake of radioactivity in adrenal glands, heart, lung and kidneys, which was blocked 63-87% by preadministration of cold PK11195. Single photon emission computer tomography (SPECT) imaging of the canine heart has been accomplished with [¹²³I]PK11195. These results suggest that [¹²³I]PK11195 has potential as a SPECT radiotracer for studying the ω₃ receptor in humans