RT Journal Article
SR Electronic
T1 cis-1-[4-(Hydroxymethyl)-2-cyclopenten-1-yl]-5-iodovinyluracil as a new imaging agent for HSV-TK reporter gene
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1949
OP 1949
VO 50
IS supplement 2
A1 Kim, Eun Jung
A1 Choi, Tae Hyun
A1 An, Gwang Il
A1 Kim, Byung Soo
A1 Ahn, Soon Hyuk
A1 Moon, Cheol
A1 Kim, Byeong Il
A1 Cheon, Gi Jeong
A1 Choi, Chang Woon
A1 Lim, Sang Moo
YR 2009
UL http://jnm.snmjournals.org/content/50/supplement_2/1949.abstract
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.