Radiosynthesis of 68Ga-labelled DOTA-biocytin (68Ga-r-BHD) and assessment of its pharmaceutical quality for clinical use

Objectives Biocytin analogues labelled with indium-111, yttrium-90 and lutetium-177 have shown their effectiveness in the imaging of infections/inflammation in patients with osteomyelitis and function as efficient tools in pretargeted antibody-guided radioimmunotherapy. In this study, the labelling of a biocytin analogue coupled with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), namely, r-BHD, with gallium-68 (Ga-68) was optimized, and the quality and stability of the preparations were assessed for clinical use. Materials and methods Synthesis of Ga-68-r-BHD was carried out by heating a fraction of the Ge-68/Ga-68 eluate in a reactor containing the biocytin analogue with the appropriate buffer. The influence of the precursor amount (from 2.5 to 140 nmol), the pH of the reaction (from 2 to 5.5) and the buffer species (1.5 mol/l sodium acetate, 1.5 mol/l sodium formate, 4.5 mol/l HEPES) on radiochemical yield and radiochemical purity was assessed. Studies on stability and binding to avidin (Av) were also conducted in different media. Results Under the best labelling condition (56 nmol of precursor, 3.8 pH, sodium formate buffer) synthesis of Ga-68-r-BHD resulted in a yield of 64 +/- 3% (not decay corrected). Radiochemical purity was around 95% because a Ga-68-coordinated sulfoxide form of the ligand was detected as a by-product of the reaction (Ga-68-r-SBHD). The by-product was identified and characterized by liquid chromatography-electrospray ionization tandem mass spectrometry. At the natural 1:4 Av/Ga-68-r-BHD molar ratio, affinity results were 62 2 and 80 +/- 2% in saline and human serum, respectively. Stability of Ga-68-r-BHD and of the radiotracer/Av complex remains almost constant over 180 min. Ga-68-r-BHD appears to be a good candidate for clinical applications. Nucl Med Commun 33:1179-1187 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.