Use of radiolabelled iododeoxyuridine as adjuvant treatment for experimental tumours of the liver.

Abstract

BACKGROUND:

The aim of the study was to determine whether hepatic regeneration stimulates growth of tumour residing within the liver, and whether a difference in the rate of DNA synthesis in liver and tumour may be used to target cancer using the radiolabelled thymidine analogue 5-iodo-2'-deoxyuridine (IUdR).

METHODS:

Partial hepatectomy was performed on Buffalo rats bearing solitary nodules of syngeneic Morris hepatoma. Liver and tumour DNA synthesis was measured by incorporation of radioactive IUdR. [(125)I]IUdR was tested as an adjuvant therapy after hepatectomy in Buffalo rats bearing diffuse microscopic Morris hepatomas to simulate the clinical situation.

RESULTS:

Liver regeneration enhanced liver and tumour DNA synthesis as measured by incorporation of radioactive IUdR. Liver DNA synthesis returned to baseline by 7 days, whereas tumour DNA synthesis remained above baseline level. Hepatectomy enhanced the growth of microscopic liver tumours. [(125)I]IUdR (250 micro Ci or 1 mCi/kg) administered 4 days after hepatectomy significantly reduced tumour growth without signs of systemic toxicity or liver dysfunction.

CONCLUSION:

The local environment of the regenerating liver stimulates tumour growth. The thymidine analogue [(125)I]IUdR may be used preferentially to target tumour DNA synthesis in the regenerating liver, and may prove useful as an adjuvant therapy for hepatic tumours after surgical resection.

• Authors: J S Zager, K A Delman, M I Ebright, S Malhotra, S Larson, Y Fong
• Journal: The British journal of surgery (Br J Surg) Vol. 90 Issue 10 Pg. 1225-31 (Oct 2003) ISSN: 0007-1323 [Print] England
• PMID: 14515291 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Chemical References

• Nucleic Acid Synthesis Inhibitors
• Idoxuridine

Topics

• Animals
• Carcinoma, Hepatocellular (metabolism, radiotherapy)
• Hepatectomy (methods)
• Hepatocytes (metabolism)
• Idoxuridine (administration & dosage, pharmacokinetics, therapeutic use)
• Injections, Intraperitoneal
• Injections, Intravenous
• Liver (metabolism)
• Liver Neoplasms, Experimental (metabolism, radiotherapy)
• Liver Regeneration
• Nucleic Acid Synthesis Inhibitors (administration & dosage, pharmacokinetics, therapeutic use)
• Portal Vein
• Rats
• Tumor Cells, Cultured