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

Nucl Med Commun. 2012 Nov;33(11):1179-87. doi: 10.1097/MNM.0b013e3283573e05.


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 (68Ga) was optimized, and the quality and stability of the preparations were assessed for clinical use.

Materials and 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.

MeSH terms

  • Avidin / metabolism
  • Clinical Trials as Topic
  • Drug Stability
  • Gallium Radioisotopes / chemistry
  • Heterocyclic Compounds, 1-Ring / chemistry*
  • Humans
  • Lysine / analogs & derivatives*
  • Lysine / blood
  • Lysine / chemistry
  • Lysine / metabolism
  • Quality Control
  • Radiochemistry / methods*
  • Safety


  • Gallium Radioisotopes
  • Heterocyclic Compounds, 1-Ring
  • Avidin
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • biocytin
  • Lysine