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

Purpose: Two variants of Annexin A5 (Cys2-AnxA5 and Cys 165-AnxA5) were labelled with Gallium-68 in order to evaluate their biological properties. Procedures: Biodistribution and pharmacokinetics of the radiotracers were studied with mu PET in healthy mice and in a mouse model of hepatic apoptosis. mu PET imaging after IV injection of the tracers in combination with mu MRI 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 Ga-68-Cys2-AnxA5 and Ga-68-Cys165-AnxA5 was low but significantly increased after therapy. Conclusion: Both Ga-68-Cys2-AnxA5 and Ga-65-Cys165-AnxA5 show a clear binding to apoptotic cells and are promising tracers for rapid evaluation of cancer therapy. (C) 2011 Elsevier Inc. All rights reserved.