Search

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.

Local recurrence of colorectal cancer may result from failure to assess accurately the extent of tumour at operation. It has been suggested that peroperative radioimmunolocalisation may improve this assessment. The degree to which this is possible has been studied using a hand-held gamma detecting probe and comparing two 125I-labelled monoclonal antibodies to colorectal tumours. The antibodies were to fetal colonic microvillus membrane (FM1D10) and to carcinoembryonic antigen (A5B7). Sixty-nine per cent (9/13) of the FM1D10 and 98% (43/44) of A5B7 labelled tumours took up significant amounts of antibody with a tumour to normal colon ratio of more than 1.5:1. The uptake was significantly better for A5B7 with a median tumour to normal colon ratio of 3.3 (1.1-13.8) compared to 1.85 (0.75-7.7) for FM1D10 (P less than 0.001). The tumour: colon ratio of both antibodies was independent of the serum CEA, Dukes' stage or the degree of histological differentiation. There was a linear correlation for tumour to normal colon ratios between the gamma detecting probe and the same tissue examined in a conventional well counter (correlation coefficient r = 0.78, P less than 0.001). Colorectal tumours demonstrate a rapid and reliable uptake of anti-CEA monoclonal antibody A5B7. This antibody can be detected with a peroperative gamma detecting probe and has the potential to improve the surgeon's appreciation of the extent of tumour and therefore may influence the surgery performed. Detailed clinical studies are now being carried out.