**3.3 Radiolabeling with 68Ga**

Gallium-68 is an interesting positron-emitter, because of its well established radiochemistry and its easy access and availability from commercial available 68Ge/68Ga-generators (t1/2 68Ge = 268 days) which renders it independent of an onsite cyclotron. The application of 68Ga-labeled peptides and proteins has attracted considerable interest for molecular imaging, because of its physical characteristics. The high positron emission fraction, 89% through positron emission of 1.9 MeV (max. energy), and half-life of 68 min allows short scanning times with sufficient amounts of radioactivity for high quality images. Generally, DOTA and NOTA are very suitable chelators and are commonly used for 68Ga3+-complexation. Though, recently TRAP (Tri-azacyclononane-phosphinic acid) and its derivatives revealed to be powerful 68Ga chelators which possess valuable utility in nuclear medicine and molecular imaging [62].

DOTA has a larger cavity than NOTA and, thus, needs higher ring distortion for complexation of 68Ga3+. Therefore, higher temperatures are required for 68Ga-DOTA complex formation compared to 68Ga complex formation with NOTA. Typically, DOTA-conjugated peptides are radiolabeled with 68Ga at 90–100°C, whereas NOTAconjugated peptides can be labeled at room temperature [62].

Generally, 68Ga is obtained by eluting a 68Ge/68Ga generator with a 0.01–1 M HCl solution. The eluate can be added directly to the NOTA- or DOTA-conjugated compound dissolved in a suitable buffer system such as HEPES (4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid), phosphate, or ammonium acetate. It is important that the resulting pH of the reaction mixture is a pH value <4 to prevent formation of colloidal hydroxide [68Ga(OH)3]n which begins at a pH value above 4.
