Unveiling the potential of copper-61 vs. gallium-68 for SSTR PET imaging

Abstract Purpose In recent years, copper-61 has attracted considerable attention from both physicists and radiochemists due to its favorable physical decay properties for PET imaging and its ease of production at any cyclotron center producing [ 18 F]FDG. The aim of this study was to evaluate the potential of 61 Cu-based radiopharmaceuticals for PET imaging of NETs, as an alternative to the commonly used gallium-68. Methods Copper-61 was produced by irradiation of natural zinc liquid targets, followed by post-processing. In vitro evaluation of 61 Cu- and 68 Ga-labeled SST analogues was performed in SSTR positive AR42J tumor cells. PET/MRI was carried out in mice bearing AR42J subcutaneous tumors. Results High molar activity [ 61 Cu]Cu-DOTA-TATE and [ 61 Cu]Cu-NOTA-TATE were successfully prepared with a radiochemical purity of over 95% and were shown to be stable for at least 6 h after the EOS. Both 61 Cu- and 68 Ga-labeled SST analogues exhibited high cellular uptake, with residual uptake when blocked with an excessive amount of peptide precursor. [ 61 Cu]Cu-NOTA-TATE showed the highest tumor uptake at 1 h p.i. (13.25 ± 1.86%ID/g) and the tumor-to-non-tumor ratio increased from 1 h to 4 h p.i. At the later time point, tumor visualization improved compared to 1 h p.i. Moreover, preclinical PET/MR images demonstrated that [ 61 Cu]Cu-NOTA-TATE has a more favorable biodistribution and imaging properties than [ 61 Cu]Cu-DOTA-TATE, with the extended PET imaging window providing a clear advantage of [ 61 Cu]Cu-NOTA-TATE over its gallium-68 analogues. Conclusion [ 61 Cu]Cu-NOTA-TATE showed similar biodistribution and pharmacokinetics to [ 68 Ga]Ga-DOTA-TATE at 1 h p.i., while demonstrating superior imaging characteristics for late PET imaging. These findings demonstrate that [ 61 Cu]Cu-NOTA-TATE holds promising characteristics for improving the detection of NETs with increased translational potential.