Feasibility study of radioimmunoguided surgery of colorectal carcinomas using indium-111 CEA-specific monoclonal antibody

Abstract

The study was undertaken to define the potential use of indium 111 carcinoembryonic antigen-specific antibody labelled [CEA F(ab')2] for the radioimmuno-detection of colorectal carcinoma using an intraoperative hand-held gamma probe. The use of a linear radioactive source allowed optimization of physical characteristics. The best results regarding sensitivity and resolution were obtained using a 5-mm thick tungsten alloy collimator. A simulation study with a liver phantom (22 MBq or 0.6 mCi) was performed to determine the effect of side scatter as opposed to direct background and showed that it is possible to detect small radioactive targets (3.7 KBq or 0.1 mu Ci) 4 cm from the phantom. A clinical study performed with ten patients showed that tumours with good uptake of CEA-specific antibody could be detected with sufficient contrast in two patients when the probe was used. Results of a biodistribution study performed after tumour fragment or normal tissue countings in a well counter showed high tumour uptake (above 8 x 10(-3) injected dose/g) and tumour-to-normal tissue ratios (between 2.5 and 20) in five patients. Results with the probe showed markedly lower ratios. There was no correlation between absolute tumour uptake and the count rates of tumour measured intraoperatively. This can be attributed to the degradation of depth resolution resulting from the high energy photopeak of gamma-emitting 111In.

Enhancement of colorectal tumor targeting using a novel biparatopic monoclonal antibody against carcinoembryonic antigen in experimental radioimmunoguided surgery

“…7,12 Stable radionuclide enables ligands and covalent linkages that minimally alter the native MAb character. 13 In all MAbs in our study, radiochemical stability was acceptably maintained and they also exhibited high avidity of their radioimmune complex from a close correlation of immune complex and silver grains in tumors. Radionuclides most suitable for the detection of small superficial tumors should emit radiation with little penetration and have a sufficiently long half-life to allow blood clearance of radioactivity so as to obtain relatively elevated tumor-to-blood ratio.…”

Intraoperative detection of somatostatin-receptor-positive neuroendocrine tumours using indium-111-labelled DTPA-D-Phe1-octreotide

“…In the present study T/B ratios varied considerably between the different scintigraphy-positive neuroendocrine tumour types; in MC tumours the ratio was 27-650, in a gastric carcinoid 71-210, in MTC 3-39 and in EPT 910 -1500. These high ratios would be expected to facilitate detection of tumours with intraoperative scintillation detection in comparison with, for example, radioimmunoguided surgery using radiolabelled monoclonal antibodies (Curtet et al, 1990;Sardi et al, 1989). Earlier limited studies on probe-guided surgery using radiolabelled octreotide in patients with neuroendocrine tumours (Ahlman et al, 1994;Schirmer et al, 1993;Waddington et al, 1994) have been promising in individual patients.…”

Peroperative nuclear medicine

“…For accurate localization it is desirable that low-energy radionuclides are employed [1][2][3]19]. The use of highenergy radionuclides reduces the specificity of the procedure since problems arise from scattered radiation from sites of high normal uptake of tracer, such as the liver [3].…”

“…The use of highenergy radionuclides reduces the specificity of the procedure since problems arise from scattered radiation from sites of high normal uptake of tracer, such as the liver [3]. Reports of radioimmunoguided surgery utilizing ~ ~ tin have concluded that the routine use of lower-energy radionuclides would be preferablein addition to more specific antibodies with higher tumour to normal tissue uptake [3,7], The use of 12~I for radioimmunoguided surgery (RIGS) appeared to be attractive from a physical point of view [1,2,19], but would appear to be contraindicated for routine use because of the high patient radiation-absorbed dose [3]. This therefore eliminates the routine use of lalI and 11 ~In, which have commonly been used for radiolabelling antibodies.…”

“…The design of the probe itself is extremely important. A number of workers have performed in vitro studies using hot spheres in a tank of varying background concentrations of activity, giving T:NT uptake ratios of the order achieved in vivo [3,17,20]. The probe should be manufactured of high-grade metal such as stainless steel or silver anodized aluminium in order to facilitate cleaning and sterilization.…”