Production of 67Cu at a biomedical cyclotron via 70Zn(p,α)67Cu reaction and its evaluation in a preclinical study using small animal SPECT/CT

Abstract

Clinical advancements in nuclear medicine theranostics has excited a research interest in exploring novel radionuclides for medical use. The duo of the β⁻ emitter ⁶⁷Cu and the positron emitter ⁶⁴Cu, has advantages over the well-established clinical pair ⁶⁸Ga and ¹⁷⁷Lu in terms of capability for high-precision therapy. Low availability has hindered the use of ⁶⁷Cu whereas ⁶⁴Cu has become established at a limited number of sites through production in low-to-medium energy biomedical cyclotrons. Via the reaction ⁷⁰Zn(p,α)⁶⁷Cu, ⁶⁷Cu 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 ⁷⁰Zn(p,α)⁶⁷Cu reaction; 2) determine experimentally the thick target yield for 16.5 MeV proton beam; 3) establish a routine production of ⁶⁷Cu 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 ⁷⁰Zn 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 [⁷⁰Zn]ZnO target. Methods were developed for solid phase extraction separation of ⁶⁷Cu 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.