Radiosynthesis of b-phenylethylamine derivatives for cardiac sympathetic nervous PET imaging

Objectives: maging presynaptic and postsynaptic functions of the cardiac autonomic nervous system are important for the evaluation of cardiac damage. We synthesized and compared four radiolabeled β-phenylethylamine derivatives for imaging purposes. [¹¹C]-N-methylphenylethylamine ([¹¹C]MPEA), [¹¹C]-N-methylhydroxyphenethylamine ([¹¹C]m-MTyr), [¹¹C]-N-methyltyramine ([¹¹C]p-MTyr) and [¹¹C]-N-methyldopamine ([¹¹C]MDA) were synthesized by aminomethylation. The biodistribution of the four radiolabeled compounds was initially evaluated in Kunming mice and validated in New Zealand white rabbits. The total synthesis time (including HPLC separation) of [¹¹C]MPEA, [¹¹C]m-MTyr, [¹¹C]p-MTyr and [¹¹C]MDA was about 30 min, 25 min, 25 min, and 30 min, respectively. The radiochemical yield of them was 25%, 13%, 33% and 18%, respectively and radiochemical purity was 99.11 ± 0.35%, 98.76 ± 0.45%, 99.06 ± 0.75% and 99.36 ± 0.41%, respectively. [¹¹C]MDA had good myocardial uptake (5.66±0.35), which was significantly higher than the lung uptake (2.78±0.03) at each time point. The heart-lung and heart-liver radioactivity uptake ratios were 2.07/1 and 1.75/1, respectively, at 10 min after injection. [¹¹C]MDA PET/CT imaging in the New Zealand white rabbits showed a clear left ventricular image and radioactivity uniformly distributed in ventricular wall, while a right ventricular image developed partially. In contrast, the biodistribution results showed radioactivity uptake of [¹¹C]-MPEA, [¹¹C]m-MTyr and [¹¹C]p-MTyr in the myocardium was lower than in the lung, liver, spleen, and kidney, but was similar to that in the muscle. These results suggest that [¹¹C]MDA has a good myocardial uptake and gets uniformly distributed in the left ventricular wall. It also has a higher target to non-target ratio, making it suitable for nuclide myocardium imaging.Keywords: β-phenylethylamine; carbon-11 labeling; cardiac sympathetic nervous; positron imaging agent

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