Biodistribution and PET imaging of [¹⁸F]-fluoroadenosine derivatives

Abstract 

Introduction

Many fluorinated analogues of adenosine nucleoside have been synthesized and studied as potential antitumor and antiviral agents. Earlier, we reported radiosynthesis of 2′-deoxy-2′-[¹⁸F]fluoro-1-β-d-arabinofuranosyl-adenine ([¹⁸F]-FAA) and 3′-deoxy-3′-[¹⁸F]fluoro-1-β-d-xylofuranosyl-adenine ([¹⁸F]FXA). Now, we report their in vivo studies including blood clearance, biodistribution and micro-PET imaging in tumor-bearing nude mice.

Methods

Tumors were grown in 6-week-old athymic nude mice (Harlan, Indianapolis, IN, USA) by inoculation of HT-29 cells, wild-type cells in the left flank and transduced cells with HSV-tk on the right flank. When the tumor was about 1 cm in size, animals were injected with these radiotracers for in vivo studies, including blood clearance, micro-PET imaging and biodistribution.

Results

Uptake of [¹⁸F]FAA in tumor was 3.3-fold higher than blood, with highest uptake in the spleen. Maximum uptake of [¹⁸F]FXA was observed in the heart compared to other organs. There was no tumor uptake of [¹⁸F]FXA. Biodistribution results were supported by micro-PET images, which also showed very high uptake of [¹⁸F]FAA in spleen and visualization of tumors, and high uptake of [¹⁸F]FXA in the heart.

Conclusion

These results suggest that [¹⁸F]FAA may be useful for tumor imaging, while [¹⁸F]FXA may have potential as a heart imaging agent with PET.

Keywords: [¹⁸F]-FAA, [¹⁸F]-FXA, Adenosine, Micro-PET