title: Fractionated 131I anti-CEA radioimmunotherapy: effects on xenograft tumour growth and haematological toxicity in mice.
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 (CFUgm), was seen. However, there was a significant depression of CFUgm 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.
authors.affiliation: Cancer Research UK, Targeting and Imaging Group, Department of Oncology, University College London (Hampstead Campus), Rowland Hill Street, London NW3 2PF, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Violet
authors.forename: J L J
authors.initials: JL
authors.lastname: Dearling
authors.forename: A J
authors.initials: AJ
authors.lastname: Green
authors.forename: R H J
authors.initials: RH
authors.lastname: Begent
authors.forename: R B
authors.initials: RB
authors.lastname: Pedley
mesh_terms: D000230:Adenocarcinoma / Q000532:radiotherapy* / Q000556:secondary; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D001853:Bone Marrow / Q000528:radiation effects; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003114:Colony-Forming Units Assay; D015179:Colorectal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D005260:Female; D006098:Granulocytes / Q000528:radiation effects; D006402:Hematologic Diseases / Q000209:etiology*; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008264:Macrophages / Q000528:radiation effects; D051379:Mice; D008819:Mice, Nude; D016499:Radioimmunotherapy; D014018:Tissue Distribution; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes