Production of Cu at a biomedical cyclotron via Zn(p,α)Cu reaction and its evaluation in a preclinical study using small animal SPECT/CT.

Clinical advancements in nuclear medicine theranostics has excited a research interest in exploring novel radionuclides for medical use. The duo of the β emitter Cu and the positron emitter Cu, has advantages over the well-established clinical pair Ga and Lu in terms of capability for high-precision therapy. Low availability has hindered the use of Cu whereas Cu has become established at a limited number of sites through production in low-to-medium energy biomedical cyclotrons. Via the reaction Zn(p,α)Cu, Cu can also be cyclotron produced, although data on the cross sections of this reaction are sparse. Our aim in this study was three-fold: 1) to establish cross sections for relevant beam energies (14-16 MeV) of the Zn(p,α)Cu reaction; 2) determine experimentally the thick target yield for 16.5 MeV proton beam; 3) establish a routine production of Cu for radiochemical and preclinical research. Additionally, our work aims to explore the feasibility of using biomedical cyclotrons for developing of novel therapeutic radionuclides. Thin layers of enriched Zn were electrodeposited onto silver foils to employ the stacked foils technique for assessing the cross section at six energies. The thick target yield was measured experimentally using a pressed [Zn]ZnO target. Methods were developed for solid phase extraction separation of Cu from the target material, as well as quality control of the product with regards to radionuclidic and radiochemical purity. Radiolabelling of PSMA-617 precursor was performed and the end product injected in a healthy mouse for a kinetic study. As a proof of concept for preclinical applications The animal was then SPECT imaged using the 185 keV gamma emission line. Summarizing, our data confirm that biomedical cyclotrons can contribute in developing novel radionuclides, even of low cross section, for preclinical research.