title: Factors influencing variability of localisation of antibodies to carcinoembryonic antigen (CEA) in patients with colorectal carcinoma--implications for radioimmunotherapy.
abstract: Tumour localisation of anti-tumour antibodies varies greatly between patients. Factors which may be responsible for this have been investigated in 56 patients with colorectal carcinoma with a view to improving radioimmunotherapy. Thirty-seven to seventy-four MBq of 125-I labelled mouse monoclonal antibody to CEA, was given intravenously and tumour resected 70-480 h later. Percentage injected activity kg-1 (% inj.act kg-1) in tumour, was inversely correlated with the time interval between injection and operation (P = 0.004). To assess the influence of other parameters on localisation, patients were divided into two time groups according to time interval between injection and operation, 70-120 h (n = 33) and 144-480 h (n = 23). In neither group was there a significant correlation of % inj.act kg-1 with time. The % inj.act kg-1 in tumour showed a significant correlation with that in the blood for both groups (P = 0.005 and P = 0.01). There was no significant correlation for either time group between % inj.act kg-1 in tumour and serum CEA values, the per cent of tumour cells positive for CEA and vascularity. Tumour to blood ratios varied considerably (range 0.3-28.5:1) suggesting that factors other than time and persistence of activity in the blood contribute to efficient targeting. Tumour to blood ratios were inversely correlated with % inj.act kg-1 in blood for the 70-120 h group (P = 0.007), and were positively correlated with % inj.act kg-1 in tumour (P = 0.012). Autoradiography showed that antibody localised predominantly on tumour cells but was distributed heterogeneously, was not solely related to the expression of antigen and in some cases accumulated in necrotic more than viable areas of tumour. Penetration of antibody into malignant acinar structures was poor and CEA-positive cells closer to the blood supply were targeted to a greater extent than distant cells. Preoperative administration of radiolabelled antibody to CEA may be helpful in selecting patients with favourable localisation for radioimmunotherapy.
authors.affiliation: University Department of Clinical Oncology, Royal Free Hospital School of Medicine, London, UK.
authors.forename: G M
authors.initials: GM
authors.lastname: Boxer
authors.forename: R H
authors.initials: RH
authors.lastname: Begent
authors.forename: A M
authors.initials: AM
authors.lastname: Kelly
authors.forename: P J
authors.initials: PJ
authors.lastname: Southall
authors.forename: S B
authors.initials: SB
authors.lastname: Blair
authors.forename: N A
authors.initials: NA
authors.lastname: Theodorou
authors.forename: P M
authors.initials: PM
authors.lastname: Dawson
authors.forename: J A
authors.initials: JA
authors.lastname: Ledermann
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use; D001345:Autoradiography; D001918:Brachytherapy / Q000379:methods; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D000922:Immunotoxins; D007457:Iodine Radioisotopes