High purity production and potential applications of copper-60 and copper-61

Previously we described the high yield production of Cu-64 using a target s ystem designed specifically for low energy, biomedical cyclotrons. In this study, the use of this target system for the production of Cu-60 and Cu-61 is described and the utility of these isotopes in the labeling of biomolecu les for tumor and hypoxia imaging is demonstrated. Cu-60 and Cu-61 were pro duced by the Ni-60(p, n)Cu-60, Ni-61(p,n)Cu-61, and Ni-60(d,n)Cu-61 nuclear reactions. The nickel target (>99% enriched or natural nickel) was plated onto a gold disk as described previously (54-225 mu m thickness) and irradi ated (14.7 MeV proton beam and 8.1 MeV deuteron beam). The copper isotopes were separated from the nickel via ion exchange chromatography and the radi oisotopic purity was assessed by gamma spectroscopy. Yields of up to 865 mC i of Cu-60 have been achieved using enriched Ni-60. Cu-61 has been produced with a maximum yield of 144 mCi using enriched Ni-61 and 72 mCi using enri ched Ni-60. Specific activities (using enriched material) ranged from 80 to 300 mCi/mu g Cu for Cu-60 and from 20 to 81 mCi/mu g Cu for Cu-61. Bombard ments of natural Ni targets were performed using both protons and deuterons , Yields and radioisotopic impurities were determined and compared with tha t for enriched materials. Cu-60 was used to radiolabel diacetyl-bis(N-4-met hylthiosemicarbazone), ATSM. Cu-60-ATSM was injected into rats that had an occluded left anterior descending coronary artery. Uptake of Cu-60-ATSM in the hypoxic region of the heart was visualized clearly using autoradiograph y. In addition, Cu-60-ATSM was injected into dogs and excellent images of t he heart and heart walls were obtained using positron emission tomography ( PET), Cu-61 was labeled to 1,4,8,11-tetraazacyclotetradecane-N,N',N ",N'''- tetraacetic acid-octreotide (TETA-octreotide) and the PET images of tumor-b earing rats were obtained up to 2 h postinjection. After decay of the Cu-61 , the same rat was injected with Cu-64-TETA-octreotide and the images were compared. The tumor images obtained using Cu-61 were found to be superior t o those using Cu-64 as predicted based on the larger abundance of positrons emitted by Cu-61 VS. Cu-64, NUCL MED BIOL 26;4:351-358, 1999. (C) 1999 Els evier Science Inc. All rights reserved.