Background: With increasing clinical demand for gallium-68, commercial germanium-68/gallium-68 ([⁶⁸Ge]Ge/[⁶⁸Ga]Ga) generators are incapable of supplying sufficient amounts of the short-lived daughter isotope. In this study, we demonstrate a high-yield, automated method for producing multi-Curie levels of [⁶⁸Ga]GaCl₃ from solid zinc-68 targets and subsequent labelling to produce clinical-grade [⁶⁸Ga]Ga-PSMA-11 and [⁶⁸Ga]Ga-DOTATATE. Results: Enriched zinc-68 targets were irradiated at up to 80 µA with 13 MeV protons for 120 min; repeatedly producing up to 194 GBq (5.24 Ci) of purified gallium-68 in the form of [⁶⁸Ga]GaCl₃ at the end of purification (EOP) from an expected > 370 GBq (> 10 Ci) at end of bombardment. A fully automated dissolution/separation process was completed in 35 min. Isolated product was analysed according to the Ph. Eur. monograph for accelerator produced [⁶⁸Ga]GaCl₃ and found to comply with all specifications. In every instance, the radiochemical purity exceeded 99.9% and importantly, the radionuclidic purity was sufficient to allow for a shelf-life of up to 7 h based on this metric alone. Fully automated production of up to 72.2 GBq [⁶⁸Ga]Ga-PSMA-11 was performed, providing a product with high radiochemical purity (> 98.2%) and very high apparent molar activities of up to 722 MBq/nmol. Further, manual radiolabelling of up to 3.2 GBq DOTATATE was performed in high yields (> 95%) and with apparent molar activities (9–25 MBq/nmol) sufficient for clinical use. Conclusions: We have developed a high-yielding, automated method for the production of very high amounts of [⁶⁸Ga]GaCl₃, sufficient to supply proximal radiopharmacies. The reported method led to record-high purified gallium-68 activities (194 GBq at end of purification) and subsequent labelling of PSMA-11 and DOTATATE. The process was highly automated from irradiation through to formulation of the product, and as such comprised a high level of radiation protection. The quality control results obtained for both [⁶⁸Ga]GaCl₃ for radiolabelling and [⁶⁸Ga]Ga-PSMA-11 are promising for clinical use.

PET imaging at late time points after injection may allow tracer clearance from normal tissue and hence improve image contrast and detectability. ⁵⁵Co is a promising isotope with high positron yield and a long half-life suitable for imaging at delayed time points. Here, we compared the 3 radioconjugates [⁶⁸Ga]Ga-DOTATATE, [⁶⁴Cu]Cu-DOTATATE, and [⁵⁵Co]Co-DOTATATE by PET/CT imaging in NOD-SCID mice bearing subcutaneous somatostatin receptor–expressing AR42J tumors. Methods:⁵⁵Co and ⁶⁴Cu were produced by the ⁵⁴Fe(d,n)⁵⁵Co and ⁶⁴Ni(p,n)⁶⁴Cu nuclear reactions, whereas ⁶⁸Ga was obtained from a ⁶⁸Ge/⁶⁸Ga generator. ⁵⁵Co and ⁶⁴Cu were labeled with DOTATATE by heating in a sodium acetate buffer and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer, respectively. AR42J tumor–bearing mice were dynamically scanned 0–1 h after injection. For ⁶⁴Cu and ⁵⁵Co, additional imaging was also performed at late time points after 4 and 24 h. Dose calculations were based on a known biodistribution. The cumulated disintegrations in each organ were calculated by integration of a fitted exponential function to the biodistribution of each respective organ. Equivalent doses were calculated by OLINDA/EXM using the MIRD formalism. Results: Tumor uptake was rapid from 0 to 1 h after injection for all 3 radioconjugates. Normal-tissue ratios as represented by tumor-to-liver, tumor-to-kidney, and tumor-to-muscle ratios increased significantly over time, with [⁵⁵Co]Co-DOTATATE reaching the highest ratio of all radioconjugates. For [⁵⁵Co]Co-DOTATATE, the tumor-to-liver ratio increased to 65 ± 16 at 4 h and 50 ± 6 at 24 h, which were 15 (P < 0.001) and 30 (P < 0.001) times higher, respectively, than the corresponding ratios for [⁶⁴Cu]Cu-DOTATATE and 5 (P < 0.001) times higher than that of [⁶⁸Ga]Ga-DOTATATE at 1 h. Correspondingly, tumor-to-kidney and tumor-to-muscle ratios for [⁵⁵Co]Co-DOTATATE were 4 (P < 0.001) and 11 (P < 0.001) times higher than that of [⁶⁴Cu]Cu-DOTATATE at 24 h. An equivalent dose was calculated as 9.6E−02 mSv/MBq for [⁵⁵Co]Co-DOTATATE. Conclusion: [⁵⁵Co]Co-DOTATATE demonstrated superior image contrast compared with [⁶⁴Cu]Cu-DOTATATE and [⁶⁸Ga]Ga-DOTATATE for PET imaging of somatostatin receptor–expressing tumors, warranting translation into clinical trials. Dosimetry calculations found that effective doses for [⁵⁵Co]Co-DOTATATE were comparable to those for both [⁶⁴Cu]Cu-DOTATATE and [⁶⁸Ga]Ga-DOTATATE.