(68)Ga-labeled peptides in tumor imaging.

UNLABELLED: Radiolabeled peptides are of increasing interest in nuclear oncology. Special emphasis has been given to the development of peptides labeled with positron emitters. Among these, (68)Ga deserves special attention, because it is available from an inhouse generator rendering (68)Ga radiopharmacy independent of an onsite cyclotron. (68)Ga has a half-life of 68 min and decays by 89% through positron emission. The parent, (68)Ge, is accelerator produced and decays with a half-life of 270.8 d by electron capture. Currently, at least 1 commercial and several in-house generators are available. (68)Ge is strongly absorbed on metal oxides or organic material, making a (68)Ge-breakthrough highly unlikely. Several groups continue to further develop generators to remove cationic impurities from the eluate. Several bifunctional chelators based on 1,4,7-triazacyclononane-N,N',N''-triacetic acid and 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) macrocycles are available for coupling to peptides and other biomolecules. In addition to these hydrophilic chelators, a lipophilic tetradentate S(3)N ligand was developed. Radiopeptides for (68)Ga labeling have been developed and tested preclinically for the targeting of somatostatin receptors, the melanocortin 1 receptor, and the bombesin receptor. Clinical studies were performed with (68)Ga-DOTA,Tyr(3)-octreotide, localizing neuroendocrine tumors with higher sensitivity than (111)In-diethylenetriaminepentaacetic acid-octreotide. In addition, (68)Ga-DOTA-based bombesin derivatives are being investigated with some success in patients with prostate cancer.
CONCLUSION: Generator-produced (68)Ga and the development of small chelator-coupled peptides (and other small biomolecules) may open a new generation of freeze-dried, good manufacturing practice-produced, kit-formulated PET radiopharmaceuticals similar to (99)Mo-/(99m)Tc-generator-based, (99m)Tc-labeled radiopharmaceuticals.