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'-[(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. 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 [(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. CONCLUSION: These results suggest that [(18)F]FAA may be useful for tumor imaging, while [(18)F]FXA may have potential as a heart imaging agent with PET.
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'-[(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. 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 [(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. CONCLUSION: These results suggest that [(18)F]FAA may be useful for tumor imaging, while [(18)F]FXA may have potential as a heart imaging agent with PET.
Authors: I A Mikhailopulo; N E Poopeiko; T I Pricota; G G Sivets; E I Kvasyuk; J Balzarini; E De Clercq Journal: J Med Chem Date: 1991-07 Impact factor: 7.446
Authors: C G Kim; D J Yang; E E Kim; A Cherif; L R Kuang; C Li; W Tansey; C W Liu; S C Li; S Wallace; D A Podoloff Journal: J Pharm Sci Date: 1996-03 Impact factor: 3.534
Authors: D A Carson; D B Wasson; L M Esparza; C J Carrera; T J Kipps; H B Cottam Journal: Proc Natl Acad Sci U S A Date: 1992-04-01 Impact factor: 11.205