Cytotoxicity and cellular uptake of pyrimidine nucleosides for imaging herpes simplex type-1 thymidine kinase (HSV-1 TK) expression in mammalian cells

Nuclear Medicine and Biology
Kevin MorinLeonard I Wiebe

Abstract

In vivo transfer of the herpes simplex virus type-1 thymidine kinase (HSV-1 TK) gene, with subsequent administration of antiviral drugs such as ganciclovir, has emerged as a promising gene therapy protocol for treating proliferative disorders. The in vitro cytotoxicities (IC(50)) for two series of 5-iodo- and (E)-5-(2-iodovinyl)-substituted 2'-deoxy- and 2'-deoxy-2'-fluoro-pyrimidine nucleosides ranged from millimolar to low nanomolar concentrations in mammalian tumor cell lines (KBALB; R-970-5; 143B; EMT-6) and their counterparts engineered to express HSV-1 TK (KBALB-STK; 143B-LTK). Their HSV-1 TK selectivity indices ranged from one (nonselective) to one million (highly selective) based on cytotoxicity, with FIRU being the least toxic to all cell lines, and FIAU being most toxic. HSV-1 TK selectivity, based on uptake, ranged from 10 to 140, with IVDU being most selective for HSV-1 TK expressing cells, followed by IVFRU, FIRU, FIAU, IVFAU and finally IUDR. Phosphorylation of [(125)I]FIAU led to incorporation of the radiolabel into nucleic acids, whereas IVFRU and FIRU radioactivity was trapped primarily in the nucleotide pool. These data indicate that cytotoxicity does not depend on initial metabolic trapping (e.g., phosphoryla...Continue Reading

References

Jan 15, 1975·International Journal of Cancer. Journal International Du Cancer·J S RhimR J Huebner
Apr 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·S Bacchetti, F L Graham
Jun 1, 1979·Journal of Cellular Physiology·C M CroceH Koprowski
Feb 21, 1990·Journal of the National Cancer Institute·F L Moolten, J M Wells
Feb 1, 1986·Antimicrobial Agents and Chemotherapy·J SamuelL I Wiebe
Nov 1, 1971·The Journal of General Virology·S A Aaronson, C A Weaver
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·L D StegmanB D Ross
Aug 30, 2001·The Journal of Biological Chemistry·A A JohnsonK A Johnson
Sep 5, 2002·Nature Reviews. Cancer·Sanjiv Sam Gambhir

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Citations

Jul 26, 2005·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Keon Wook KangSanjiv S Gambhir
Jul 11, 2006·Nuclear Medicine Communications·Mary F DempseyS M Brown
Jan 20, 2010·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Eun Jung KimSang Moo Lim
Apr 25, 2006·Nuclear Medicine and Biology·Michaela SchmidSven N Reske
Jan 18, 2005·Cancer Cell·Shimon Gross, David Piwnica-Worms
Jan 29, 2008·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Jung Young KimDae Hyuk Moon
Nov 21, 2019·Cancer Biotherapy & Radiopharmaceuticals·Min-Jung SeoJoo Hyun Kang

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