Synthesis and evaluation of cis-1-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-[(124)I]iodouracil: a new potential PET imaging agent for HSV1-tk expression.
In our pursuit to find an appropriate reporter probe for herpes simplex virus type-1 thymidine kinase (HSV1-tk), a carbocyclic nucleoside analogue, cis-1-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-[124I]iodouracil, has been efficiently synthesized. A Pd(0)-catalyzed coupling reaction together with organotin and exchange reactions for radiolabeling gave more than 80% radiochemical yield with greater than 95% radiochemical purity and 1.15 GBq/mumol specific activity. Biological data reveal that the analogue is stable in vitro, less toxic than ganciclovir (GCV), and selective to HSV1-tk-expressed cells based on micro positron emission tomography (microPET) image analyses. Thus, this new carbocyclic nucleoside, referred to in this paper as carbocyclic 2',3'-didehydro-2',3'-dideoxy-5-iodouridine (carbocyclic d4IU) is a potential imaging probe for HSV1-tk.
Ahn
Hyunseok
H
Hanyang University, Department of Chemistry and Applied Chemistry, Ansan, Sangrok-Gu, Sa-3-Dong 1271, Kyunggi-Do 426-791, Korea.
Choi
Tae Hyun
TH
De Castro
Kathlia
K
Lee
Kyo Chul
KC
Kim
Byoungsoo
B
Moon
Byung Seok
BS
Hong
Su Hee
SH
Lee
Jong Chan
JC
Chun
Kwon Soo
KS
Cheon
Gi Jeong
GJ
Lim
Sang Moo
SM
An
Gwang Il
GI
Rhee
Hakjune
H
D000818:Animals; D045744:Cell Line, Tumor; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D008862:Microsomes, Liver / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D044967:Serum; D013937:Thymidine Kinase / Q000096:biosynthesis*; D014018:Tissue Distribution; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity
C526814:1-(4-(hydroxymethyl)-2-cyclopenten-1-yl)-5-iodouracil; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D013937:Thymidine Kinase; D014529:Uridine