High-resolution magnetic resonance imaging of the efficacy of the cytosine analogue 1-[2-C-cyano-2-deoxy-beta-D-arabino-pentofuranosyl]-N(4)-palmitoyl cytosine (CS-682) in a liver-metastasis athymic nude mouse model.

Abstract

High-resolution magnetic resonance (MR) imaging techniques in a liver metastatic mouse model were used to assess CS-682, a novel 2'-deoxycytidine analogue of 1-[2-C-cyano-2-deoxy-beta-D-arabino-pentofuranosyl]-N(4)-palmitoyl cytosine. The efficacy of CS-682 was visualized in real time by MR imaging of initial seeding and subsequent growth of liver metastases. The relative therapeutic efficacies of CS-682 and two agents used clinically, gemcitabine [2'-deoxy-2',2'-difluorocytidine monohydrochloride (DFDC)] and 5-fluorouracil (5-FU), were compared in this model. CS-682 was found to exhibit superior efficacy by delaying the onset and inhibiting the growth of liver metastasis compared with gemcitabine, 5-FU, and control. The overall occurrence of metastases was decreased 62% by CS-682, 18% by DFDC, and 35% by 5-FU. CS-682 increased the life span of the treated animals significantly, by 28 days above the 29-day median survival without treatment, compared with 11 days by DFDC and 14 days by 5-FU. The increased survival in CS-682-treated animals correlated with the antimetastatic activity of this compound. These preclinical findings support the potential clinical utility of CS-682 in the treatment of liver metastasis.

• Authors: Ming Wu, Richard Mazurchuk, Neeta D Chaudhary, Joseph Spernyak, Jean Veith, Paula Pera, William Greco, Robert M Hoffman, Tomowo Kobayashi, Ralph J Bernacki
• Journal: Cancer research (Cancer Res) Vol. 63 Issue 10 Pg. 2477-82 (May 15 2003) ISSN: 0008-5472 [Print] United States
• PMID: 12750269 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Arabinonucleosides
• Deoxycytidine
• Cytosine
• Fluorouracil
• sapacitabine
• Gemcitabine

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Arabinonucleosides (pharmacology)
• Cell Division (drug effects)
• Colonic Neoplasms (drug therapy, pathology)
• Cytosine (analogs & derivatives, pharmacology)
• Deoxycytidine (analogs & derivatives, pharmacology)
• Female
• Fluorouracil (pharmacology)
• Humans
• Liver Neoplasms (pathology, prevention & control, secondary)
• Magnetic Resonance Imaging (methods)
• Mice
• Mice, Nude
• Xenograft Model Antitumor Assays
• Gemcitabine