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

Compared to NOTA- and DOTA-peptides, achievable specific activity (AS) for TRAP-peptide is approximately 10 and 20 times higher, respectively. AS values in the range of 5,000？GBq/μmol were routinely obtained using 1？GBq of 68Ga, equivalent to 0.11？μg of cold mass for a 185-MBq patient dose of a 3-kDa conjugate. The TRAP-peptide could be 68Ga-labeled with excellent reproducibility and？>？95% radiochemical yield for precursor amounts as low as 1？nmol.High 68Ga 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.With the commercial availability of 68Ge/68Ga generators, cyclotron-independent on-site production of tracers for positron-emission tomography (PET) has become widely feasible [1,2]. Thus, in the near future, a ubiquitous implementation of PET and PET/CT even in regions with less well-developed infrastructure can be expected, similar to the global story of success of 99mTc-based scintigraphy which started half a century ago with the introduction of 99Mo/99mTc generators [1,3]. In the long run, a partial substitution of single photon emission computed tomography (SPECT) by PET (and SPECT/CT by PET/CT, respectively) appears to be a realistic scenario in view of the advantages of PET, such as superior spatial resolution and sensitivity. Besides, in contrast to reactor-produced 99Mo, 68Ge is cyclotron-produced. This can be considered advantageous with regard to the recent insufficiency of global reactor capacity for reliable 99Mo supply [4], and independence of 68Ga-PET from nuclear reactors might positively influence the bias of its public perception.Generally, 68Ga labeling is done by complexation of the 68Ga3+ ion. For this purpose, dedicated chelators usually