Site-specific 68Ga-labeled Annexin A5 as a PET imaging agent for apoptosis

Abstract Purpose Two variants of Annexin A5 (Cys2-AnxA5 and Cys165-AnxA5) were labelled with Gallium-68 in order to evaluate their biological properties. Procedures Biodistribution and pharmacokinetics of the radiotracers were studied with μPET in healthy mice and in a mouse model of hepatic apoptosis. μPET imaging after IV injection of the tracers in combination with μMRI was performed in Daudi tumor bearing mice before and after treatment with a combination of chemotherapy and radiotherapy. Results The biodistribution data indicated a fast urinary clearance with only minor hepatobilliary clearance, although a high retention in the kidneys was observed. Animals treated with anti-Fas showed a 3 to 8 times higher liver uptake as compared to healthy animals. Tumor uptake of 68 Ga-Cys2-AnxA5 and 68 Ga-Cys165-AnxA5 was low but significantly increased after therapy. Conclusion Both 68 Ga-Cys2-AnxA5 and 68 Ga-Cys165-AnxA5 show a clear binding to apoptotic cells and are promising tracers for rapid evaluation of cancer therapy.