Preparation and biological evaluation of 2-amino-6-[18F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[18F]FPCV) as a novel PET probe for imaging HSV1-tk reporter gene expression.
BACKGROUND
2-Amino-6-[(18)F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[(18)F]FPCV) was prepared via a one-step nucleophilic substitution and evaluated as a novel probe for imaging the expression of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene.


METHODS
Log P of 6-[(18)F]FPCV was calculated in octanol/phosphate-buffered saline (PBS). Stability studies were performed in PBS and bovine serum albumin (BSA). Cell uptake was performed at various time points in wild-type cells and transduced cells. For in vivo studies, tumors were grown in nude mice by inoculation with C6 cells, wild type and tk positive. The radiotracer was intravenously injected to animals, and micro-PET imaging was performed. Biodistribution of 6-[(18)F]FPCV was performed on another group of animals at different time points.


RESULTS
Log P of 6-[(18)F]FPCV was -0.517. 6-[(18)F]FPCV was fairly stable in PBS and BSA at 6 h. The tracer uptake in C6-tk cells was 5.5-18.8 times higher than that in wild-type cells. The plasma half-life of 6-[(18)F]FPCV was as follows: alpha t(1/2)=1.2 min and beta t(1/2)=73.7 min. The average ratio of tumor uptake between the transduced tumor and the wild-type tumor was 1.69 at 15 min.


CONCLUSIONS
Biological evaluation showed that 6-[(18)F]FPCV is a potential probe for imaging HSV1-tk gene expression. However, its in vivo defluorination may limit its application in PET imaging of gene expression.
Cai
Hancheng
H
Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.
Yin
Duanzhi
D
Zhang
Lan
L
Yang
Xiaofeng
X
Xu
Xiaoyan
X
Liu
Weiguo
W
Zheng
Xuesheng
X
Zhang
Hong
H
Wang
Jing
J
Xu
Yuhong
Y
Cheng
Dengfeng
D
Zheng
Mingqiang
M
Han
Yanjiang
Y
Wu
Mingxing
M
Wang
Yongxian
Y
D000818:Animals; D015153:Blotting, Western; D002021:Buffers; D045744:Cell Line, Tumor; D017930:Genes, Reporter / Q000235:genetics; D006207:Half-Life; D006561:Herpes Simplex / Q000000981:diagnostic imaging / Q000821:virology; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics*; D007150:Immunohistochemistry; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010710:Phosphates; D049268:Positron-Emission Tomography; D011687:Purines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011786:Quality Control; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D012710:Serum Albumin, Bovine; D012965:Sodium Chloride; D013937:Thymidine Kinase / Q000235:genetics*; D014018:Tissue Distribution
C524180:2-amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbutyl)purine; D002021:Buffers; D010710:Phosphates; D011687:Purines; D019275:Radiopharmaceuticals; D012710:Serum Albumin, Bovine; D012965:Sodium Chloride; D013937:Thymidine Kinase