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Background  Currently,  68 Ga-labeled 1,4,7,10-tetraazacyclododecane-tetraacetic acid (DOTA)-peptides are the most widely used class of  68 Ga radiotracers for PET, although DOTA is not optimal for  68 Ga complexation. More recently, 1,4,7-triazacyclononane-triacetic acid (NOTA) and particularly triazacyclononane-phosphinate (TRAP) chelators have been shown to possess superior  68 Ga binding ability. Here, we report on the efficiency, reproducibility, and achievable specific activity for fully automated  68 Ga labeling of DOTA-, NOTA-, and TRAP-peptide conjugates.    Findings  Compared to NOTA- and DOTA-peptides, achievable specific activity ( A  S ) for TRAP-peptide is approximately 10 and 20 times higher, respectively.  A  S  values in the range of 5,000 GBq/μmol were routinely obtained using 1 GBq of  68 Ga, equivalent to 0.11 μg of cold mass for a 185-MBq patient dose of a 3-kDa conjugate. The TRAP-peptide could be  68 Ga-labeled with excellent reproducibility and > 95% radiochemical yield for precursor amounts as low as 1 nmol.    Conclusions  High  68 Ga labeling efficiency of TRAP-peptides could facilitate realization of kit labeling procedures. The good reproducibility of the automated synthesis is of relevance for GMP production, and the possibility to provide very high specific activities offers a high degree of safety in first clinical trials, due to reduction of cold mass content in tracer formulations.

Comparative gallium-68 labeling of TRAP-, NOTA-, and DOTA-peptides: practical consequences for the future of gallium-68-PET