¹Cancer Research UK Targeting and Imaging Group, Department of Oncology, University College London (Hampstead Campus), Rowland Hill Street, London NW3 2PF, UK

Correspondence: Dr RB Pedley, UCL Cancer Institute, University College London, Paul O'Gorman Building, 72 Huntley St, London WC1E 6BT, UK. E-mail: r.b.pedley@ucl.ac.uk

Received 9 April 2008; Revised 16 June 2008; Accepted 17 June 2008; Published online 5 August 2008.

Abstract

Dose fractionation has been proposed as a method to improve the therapeutic ratio of radioimmunotherapy (RIT). This study compared a single administration of 7.4 MBq ¹³¹I-anti-CEA antibody given on day 1 with the same total activity given as fractionated treatment: 3.7 MBq (days 1 and 3), 2.4 MBq (days 1, 3, and 5) or 1.8 MBq (days 1, 3, 5, and 8). Studies in nude mice, bearing the human colorectal xenograft LS174T, showed that increasing the fractionation significantly reduced the efficacy of therapy. Fractionation was associated with a decrease in systemic toxicity as assessed by weight, but did not lead to any significant decrease in acute haematological toxicity. Similarly, no significant decrease in marrow toxicity, as assessed by colony-forming unit assays for granulocytes and macrophages (CFU_gm), was seen. However, there was a significant depression of CFU_gm counts when all treated animals were compared with untreated controls, suggesting that treatment did suppress marrow function. In conclusion, in this tumour model system, fractionated RIT causes less systemic toxicity, but is also less effective at treating tumours.