Biodistribution and PET imaging of (18)F-fluoroadenosine derivatives

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'-[(18)F]fluoro-1-beta-D-arabinofuranosyl-adenine ([(18)F]-FAA) and 3'-deoxy-3'-[(18)F]fluoro-1-beta-d-xylofuranosyl-adenine ([(18)F]FXA). Now, we report their in vivo studies including blood clearance, biodistribution and micro-PET imaging in tumor-bearing nude mice.INTRODUCTIONMany fluorinated analogues of adenosine nucleoside have been synthesized and studied as potential antitumor and antiviral agents. Earlier, we reported radiosynthesis of 2'-deoxy-2'-[(18)F]fluoro-1-beta-D-arabinofuranosyl-adenine ([(18)F]-FAA) and 3'-deoxy-3'-[(18)F]fluoro-1-beta-d-xylofuranosyl-adenine ([(18)F]FXA). Now, we report their in vivo studies including blood clearance, biodistribution and micro-PET imaging in tumor-bearing nude mice.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.METHODSTumors 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.Uptake of [(18)F]FAA in tumor was 3.3-fold higher than blood, with highest uptake in the spleen. Maximum uptake of [(18)F]FXA was observed in the heart compared to other organs. There was no tumor uptake of [(18)F]FXA. Biodistribution results were supported by micro-PET images, which also showed very high uptake of [(18)F]FAA in spleen and visualization of tumors, and high uptake of [(18)F]FXA in the heart.RESULTSUptake of [(18)F]FAA in tumor was 3.3-fold higher than blood, with highest uptake in the spleen. Maximum uptake of [(18)F]FXA was observed in the heart compared to other organs. There was no tumor uptake of [(18)F]FXA. Biodistribution results were supported by micro-PET images, which also showed very high uptake of [(18)F]FAA in spleen and visualization of tumors, and high uptake of [(18)F]FXA in the heart.These results sugg