title: Radiosynthesis of 68Ga-labelled DOTA-biocytin (68Ga-r-BHD) and assessment of its pharmaceutical quality for clinical use.
abstract: OBJECTIVE
  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 (68Ga) was optimized, and the quality and stability of the preparations were assessed for clinical use.
  
  
  METHODS
  Synthesis of 68Ga-r-BHD was carried out by heating a fraction of the 68Ge/68Ga 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 68Ga-r-BHD resulted in a yield of 64 ± 3% (not decay corrected). Radiochemical purity was around 95% because a 68Ga-coordinated sulfoxide form of the ligand was detected as a by-product of the reaction (68Ga-r-SBHD). The by-product was identified and characterized by liquid chromatography-electrospray ionization tandem mass spectrometry. At the natural 1 : 4 Av/68Ga-r-BHD molar ratio, affinity results were 62 ± 2 and 80 ± 2% in saline and human serum, respectively. Stability of 68Ga-r-BHD and of the radiotracer/Av complex remains almost constant over 180 min. 68Ga-r-BHD appears to be a good candidate for clinical applications.
authors: Nuclear Medicine Unit, Advanced Technology Department, Santa Maria Nuova Hospital-IRCCS, Reggio Emilia, Italy. asti.mattia@asmn.re.it
authors: Mattia
authors: M
authors: Asti
authors: Michele
authors: M
authors: Iori
authors: Paola A
authors: PA
authors: Erba
authors: Giulia
authors: G
authors: Atti
authors: Daniela
authors: D
authors: Farioli
authors: Claudio
authors: C
authors: Guidotti
authors: Annibale
authors: A
authors: Versari
mesh_terms: D001360:Avidin / Q000378:metabolism; D002986:Clinical Trials as Topic; D004355:Drug Stability; D005710:Gallium Radioisotopes / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D011786:Quality Control; D011854:Radiochemistry / Q000379:methods*; D012449:Safety
chemical_list: D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D001360:Avidin; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C013411:biocytin; D008239:Lysine