Evaluation of F-18 labelled annexin V: apoptosis imaging in mice

Apoptosis imaging with PET plays an increasing role in various medical fields like oncology, cardiology, transplant rejection, and inflammation, but the radiotracer distribution in the tis-sues is influenced by various mechanisms. In this study a recombinant annexin-V (courtesy N. Budisa, Max Planck Institute of Biochemistry) derivative and human serum albumin (HSA) were radiolabelled using N-succinimidyl-4-F-18-fluorobenzoate (SFB), and characterized. Mechanism and specificity of both F-18-annexin-V and F-18-HSA biodistribution and accu-mulation were examined in rodents.

Recombinant annexin-V derivative and HSA were radiolabelled using SFB and the products were confirmed by size exclusion chromatography and SDS-PAGE. The radiotracer distribu-tions in animals were studied in rats and mice ex vivo by organ extraction, autoradiography, and in vivo with animal PET. For apoptosis imaging, F-18-annexin-V or F-18-HSA were in-travenously applied in 4 groups of mice that received either intraperitoneal 100 µg Anti-Fas antibody in 200 µL isotonic NaCl or 200 µL isotonic NaCl 2 hours before the radiotracer. The degree of liver apoptosis was characterized by plasma ALAT and ASAT activity measure-ments.

The radiochemical yield was in the range of 10 to 30% (corrected for decay) with a specific activity of more than 20 GBq/µmol. The accumulation of F-18-annexin-V and F-18-HSA, respectively in the apoptotic livers (4 – 16%ID/g) were correlated to the ASAT and increased up to 4 times in comparison to control. The biodistribution of the tracers were comparable except for the renal elimination of F-18-annexin-V, which was up to 3 times higher than of F-18-HSA.