Optimization of the Automated Synthesis of [11C]mHED—Administered and Apparent Molar Activities

Abstract

The tracer [[11C]meta-Hydroxyephedrine ([[11C]mHED) is one of the most applied PET tracers for cardiac imaging, whose radiosynthesis was already reported in 1990. While not stated in the literature, separation difficulties and an adequate formulation of the product are well known challenges in its production. Furthermore, the precursor (metaraminol) is also a substrate for the norepinephrine transporter, and can therefore affect the image quality. This study aims at optimizing the synthetic process of [[11C]mHED and investigating the effect of the apparent molar activity (sum of mHED and metaraminol) in patients and animals. The main optimization was the improved separation through reverse phase-HPLC by a step gradient and subsequent retention of the product on a weakly-cationic ion exchange cartridge. The µPET/µCT was conducted in ten rats (ischemic model) and the apparent molar activity was correlated to the VOI- and SUV-ratio of the myocardium/intra-ventricular blood pool. Moreover, nine long-term heart transplanted and five Morbus Fabry patients underwent PET and MRI imaging for detection of changes in the sympathetic innervation. In summary, the fully-automated synthesis and optimized purification method of [[11C]mHED is easily applicable and reproducible. Moreover, it was shown that the administered apparent molar activities had a negligible effect on the imaging quality.

EANM guideline for harmonisation on molar activity or specific activity of radiopharmaceuticals: impact on safety and imaging quality

“…Both metaraminol as well as mHED itself can lead to increase of both systolic and diastolic blood pressure, therefore the sum of both compounds has to be evaluated after purification of the radiotracer and considered for safe administration of [ 11 C]mHED (apparent A m ) (Khavandi et al 2009). Doses of 0.25-1 mg of metaraminol (Vraka et al 2019) were safe to inject to patients. In most PET measurements, a pharmacological effect must be avoided and therefore a dose below a pharmacological or even toxic dose is a necessity (microdosing concept) (Critchley et al 1999).…”