PT - JOURNAL ARTICLE AU - Eun Jung Kim AU - Tae Hyun Choi AU - Gwang Il An AU - Byung Soo Kim AU - Soon Hyuk Ahn AU - Cheol Moon AU - Byeong Il Kim AU - Gi Jeong Cheon AU - Chang Woon Choi AU - Sang Moo Lim TI - cis-1-[4-(Hydroxymethyl)-2-cyclopenten-1-yl]-5-iodovinyluracil as a new imaging agent for HSV-TK reporter gene DP - 2009 May 01 TA - Journal of Nuclear Medicine PG - 1949--1949 VI - 50 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/50/supplement_2/1949.short 4100 - http://jnm.snmjournals.org/content/50/supplement_2/1949.full SO - J Nucl Med2009 May 01; 50 AB - 1949 Objectives While IVDU is an effective substrate for HSV-TK, it is not suitable for in vivo study because of C-N glycocidic bond cleavage by thymidine phosphorylase. A carbocyclic IVDU analogue, ddIVDU, is synthesized and possesses greater metabolic stability due to replacement of the furanose oxygen with carbon. Methods A carbocyclic iodonucleoside analogue, cis-1-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-iodovinyluracil (ddIVDU) was synthesized from cyclopentadiene and glyoxylic acid as starting materials in 10 steps. The synthetic route for precursor employed cyclopentadiene as a starting material and proceed in good yield through 9 steps which contain hetero Diels-Alder reaction and Pd(0)-catalyzed coupling reaction as key reactions. For cytotoxicity analysis, MCA and MCA-TK (HSV-TK positive) cells were treated with various concentration of IVDU, ddIVDU, and GCV. Cytotoxicity was measured by the MTS methods. For in vitro uptake study, MCA and MCA-TK cells were incubated with 1uCi of [125I]IVDU and [125I]ddIVDU. The accumulation of each agent was measured after various incubation times. Results IVDU and GCV were more toxic than ddIVDU in MCA-TK cells. But, in MCA cells, ddIVDU was more toxic than IVDU. Cell uptake of [125I]IVDU was higher than [125I]ddIVDU in MCA-TK cell. And also, higher accumulation of [125I]ddIVDU was observed more in the acid-insoluble fraction than the acid-soluble fraction of MCA-TK cell lysates. By contrast with [125I]ddIVDU, [125I]IVDU showed high accumulation in the acid-soluble fraction. Conclusions These results revealed that metabolic stability of ddIVDU was improved than IVDU.