Herpes simplex virus thymidine kinase imaging in mice with (1-(2'-deoxy-2'-[ super(18)F]fluor o-1- beta -D-arabinofuranosyl)-5-iodouracil) and metabolite (1-(2'-deoxy-2'-[ super(18)F]fluor o-1- beta -D-arabinofuranosyl)-5-uracil)

• Published in: European journal of nuclear medicine and molecular imaging Vol. 36; no. 12; pp. 1987 - 1993
• Main Authors: Nimmagadda, Sridhar, Mangner, Thomas J, Lawhorn-Crews, Jawana M, Haberkorn, Uwe, Shields, Anthony F
• Format: Journal Article
• Language: English
• Published: 01.12.2009
• Subjects: Herpes simplex virus
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-009-1177-y

Purpose: FIAU, (1-(2'-deoxy-2'-fluoro-1- beta -D-arabinofuranosyl) -5-iodouracil) has been used as a substrate for herpes simplex virus thymidine kinases (HSV-TK and HSV-tk, for protein and gene expression, respectively) and other bacterial and viral thymidine kinases for noninvasive imaging applications. Previous studies have reported the formation of a de-iodinated metabolite of super(18)F-FIAU. This study reports the dynamic tumor uptake, biodistribution, and metabolite contribution to the activity of super(18)F-FIAU seen in HSV-tk gene expressing tumors and compares the distribution properties with its de-iodinated metabolite super(18)F-FAU. Methods: CD-1 nu/nu mice with subcutaneous MH3924A and MH3924A-stb-tk+ xenografts on opposite flanks were used for the biodistribution and imaging studies. Mice were injected IV with either super(18)F-FIAU or super(18)F-FAU. Mice underwent dynamic imaging with each tracer for 65min followed by additional static imaging up to 150min post-injection for some animals. Animals were sacrificed at 60 or 150min post-injection. Samples of blood and tissue were collected for biodistribution and metabolite analysis. Regions of interest were drawn over the images obtained from both tumors to calculate the time-activity curves. Results: Biodistribution and imaging studies showed the highest uptake of super(18)F-FIAU in the MH3924A-stb-tk+ tumors. Dynamic imaging studies revealed a continuous accumulation of super(18)F-FIAU in HSV-TK expressing tumors over 60min. The mean biodistribution values (SUV plus or minus SE) for MH3924A-stb-tk+ were 2.07 plus or minus 0.40 and 6.15 plus or minus 1.58 and that of MH3924A tumors were 0.19 plus or minus 0.07 and 0.47 plus or minus 0.06 at 60 and 150min, respectively. In super(18)F-FIAU injected mice, at 60min nearly 63% of blood activity was present as its metabolite super(18)F-FAU. Imaging and biodistribution studies with super(18)F-FAU demonstrated no specific accumulation in MH3924A-stb-tk+ tumors and SUVs for both the tumors were similar to those observed with muscle. Conclusion: super(18)F-FIAU shows a continuous accumulation of activity in HSV-TK expressing tumors. super(18)F-FAU does not show any preferential accumulation in HSV-TK expressing tumors. In the super(18)F-FIAU treated mice, the super(18)F-FAU contribution to the total uptake seen in HSV-TK positive tumors is minimal.