Synthesis and evaluation of a novel 68Ga-NODAGA-Erlotinib analogue towards PET imaging of Epidermal Growth Factor Receptor over-expressing cancers

Abstract

In this paper we report the synthesis of 68Ga labeled NODAGA-Erlotinib for imaging of EGFR over-expressing tumors. NODAGA-Erlotinib conjugate was synthesized by reaction of the terminal alkyne of Erlotinib using Cu catalyzed click reaction. The conjugate was then radiolabeled with 68Ga in high radiochemical yields. The 68Ga NODAGA-Erlotinib conjugate also exhibited high in vitro stability. The log P value of 68Ga-NODAGA-Erlotinib was lower than that of 68Ga-NOTA-Erlotinib, a 68Ga based Erlotinib conjugate previously reported by our group. In the in vitro cell binding studies carried out in EGFR-positive A431 cells, 68Ga-NODAGA-erlotinib exhibited an uptake (7.8±1.3 %) lower than that of 68Ga-NOTA-Erlotinib (9.8±0.4%) showing that an increase in hydrophilicity possibly effected a decrease in cell permeability. The higher hydrophilicity of 68Ga-NODAGA-Erlotinib also led to significantly lower accumulation of 68Ga-NODAGA-Erlotinib in non-target organs in the biodistribution studies in Swiss mice. The overall properties of the 68Ga-NODAGA-Erlotinib conjugate are promising and reflect the role of hydrophilicity in reducing the non-specific uptake of the final radiotracer towards improving signal/noise ratio for further imaging studies.