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

• Published in: British journal of surgery Vol. 90; no. 10; pp. 1225 - 1231
• Main Authors: Zager, J. S., Delman, K. A., Ebright, M. I., Malhotra, S., Larson, S., Fong, Y.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.10.2003; Wiley
• Subjects: Animals; Biological and medical sciences; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - radiotherapy; Diseases of the digestive system; Hepatectomy - methods; Hepatocytes - metabolism; Idoxuridine - administration & dosage; Idoxuridine - pharmacokinetics; Idoxuridine - therapeutic use; Injections, Intraperitoneal; Injections, Intravenous; Liver - metabolism; Liver Neoplasms, Experimental - metabolism; Liver Neoplasms, Experimental - radiotherapy; Liver Regeneration; Medical sciences; Nucleic Acid Synthesis Inhibitors - administration & dosage; Nucleic Acid Synthesis Inhibitors - pharmacokinetics; Nucleic Acid Synthesis Inhibitors - therapeutic use; Portal Vein; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Rats; Tumor Cells, Cultured; Animal model; Radiolabelling; Rat; Liver; Rodentia; Adjuvant treatment; Hepatic disease; Thymidine; Malignant tumor; Experimental study; Hepatectomy; Vertebrata; Mammalia; Treatment; Surgery; Analog; Animal; Digestive diseases
• ISSN: 0007-1323; 1365-2168
• DOI: 10.1002/bjs.4207

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. [125I]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. [125I]IUdR (250 µCi 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 [125I]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. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. Guidance for future clinical studies