Production of [13N]ammonia from [13C]methanol on a 7.5 MeV cyclotron using 13C(p, n)13N reaction: Detection of myocardial infarction in a mouse model.

[¹³N]Ammonia is commonly produced using ¹⁶O(p, α)¹³N reaction but one of the limiting factor of this reaction is the relatively small nuclear cross-section at proton energies of <10 MeV. An alternative production method using ¹³C(p, n)¹³N reaction, which has a higher nuclear cross-section at low proton energies, is more suitable for a preclinical PET imaging facility equipped with a <10 MeV cyclotron. Here, we report a novel method to produce [¹³N]ammonia from [¹³C]methanol for preclinical use on a 7.5 MeV cyclotron. A tantalum solution target (80 μl) consisting of a havar window supplied by the cyclotron manufacturer for the production of [¹⁸F]fluoride was used without any modifications. The final bombardment parameters were optimized as follow: [¹³C]methanol concentration in target solution - 10%, bombardment time - 8 min, and beam current - 2.2 μA. These parameters provided doses of [¹³N]ammonia which were sufficient to conduct preclinical PET imaging studies in a mouse model of myocardial infarction. Under optimized conditions, the operational lifetime of the target was approximately 150 μAmin. Radionuclide identity of the product as ¹³N was confirmed by measuring the decay half-life and its radionuclide purity was confirmed by γ-ray spectroscopic analysis. Gas chromatography revealed that the final [¹³N]ammonia dose was not distinguishable from water, showing no traces of methanol. As expected, PET/CT imaging in healthy CD-1 mice indicated the accumulation of [¹³N]ammonia in myocardial tissue; mice with myocardial infarction created by left ascending coronary ligation showed clear perfusion deficit in affected tissue. This work demonstrates the proof-of-concept of using ¹³C(p, n)¹³N reaction to produce [¹³N]ammonia from [¹³C]methanol with a <10 MeV cyclotron, and its diagnostic application in imaging cardiac perfusion.