Radiolabelling DOTA-peptides with 68Ga

Purpose. A new field of interest is the application of Ga-68-labelled DOTA-conjugated peptides for positron emission tomography (PET). The commercially available or house-made generators require time-consuming and tedious handling of the eluate. Radiolabelling at high specific activities without further purification is not possible, while high specific activities are necessary for peptides that potentially display pharmacological side-effects. Here we present the practical aspects and the results of radiolabelling DOTA-peptides with a TiO2-based commercially available Ge-68/Ga-68 generator. Methods. Reaction kinetics and parameters influencing the incorporation of the radionuclide at the highest achievable specific activity were investigated. Since high finger doses were anticipated during handling of the high beta-energy emitter Ga-68, finger dosimetric measurements were performed during radiolabelling and in vivo administration. Results. Fractionated elution of the generator revealed that 80% of the radioactivity was recovered in 1 ml. Bi- and trivalent ionic contaminants that compete for the incorporation of the radionuclide were below 50 M; thus further tedious and time-consuming purification was avoided. Radiolabelling was performed at pH 3.5-4. Plastic shielding (>= 7-mm wall thickness) around the syringe during administration effectively eliminated the positrons. In rats (GaCl3)-Ga-68 had slow clearance from blood, while Ga-68-EDTA was rapidly cleared via the kidneys. Uptake of Ga-68-DOTATOC in somatostatin receptor-positive tissues was high, with no significant difference between 1 and 4 h post injection. Conclusion. DOTA-peptides for PET imaging can be labelled with Ga-68 up to specific activities of 1 GBq per nmol within 20 min, enabling the clinical application of peptides that display potential pharmacological side-effects.