A new 68Ga-labeled ornithine derivative for PET imaging of ornithine metabolism in tumors

Ornithine metabolism plays a vital role in tumorigenesis. For cancer cells, ornithine is mainly used as a substrate for ornithine decarboxylase (ODC) for the synthesis of polyamines. The ODC as a key enzyme of polyamine metabolism has become an important target for cancer diagnosis and treatment. To non-invasively detect the levels of ODC expression in malignant tumors, we have synthesized a novel Ga-68-labeled ornithine derivative ([Ga-68]Ga-NOTA-Orn). The synthesis time of [Ga-68]Ga-NOTA-Orn was about 30 min with a radiochemical yield of 45-50% (uncorrected), and the radiochemical purity was > 98%. [Ga-68]Ga-NOTA-Orn was stable in saline and rat serum. Cellular uptake and competitive inhibition assays using DU145 and AR42J cells demonstrated that the transport pathway of [Ga-68]Ga-NOTA-Orn was similar to that of l-ornithine, and it could interact with the ODC after transporting into the cell. Biodistribution and micro-positron emission tomography (Micro-PET) imaging studies showed that [Ga-68]Ga-NOTA-Orn exhibited rapid tumor uptake and was rapidly excreted through the urinary system. All above results suggested that [Ga-68]Ga-NOTA-Orn is a novel amino acid metabolic imaging agent with great potential of tumor diagnosis.