Radioimmunolocalization and quantification of liver metastases and subcutaneous tumours from a human colonic cancer xenografted in the nude rat.
The purpose of the present investigation was to improve the conditions for radioimmunolocalization (RIL) and radioimmunotherapy (RIT) of colonic cancer, using experimental models of the human disease. A tumour model was created in the nude rat by intraportal injection of a mechanically disintegrated cell preparation of the human colonic cancer cell-line LS 174 T, producing liver metastases in a dose-dependent fashion. A conventional subcutaneous (s.c.) tumour model was also employed, where LS 174 T cells were inoculated into a hindleg of nude rats. A technique was developed for quantification of liver metastases by means of contrast-enhanced CT, using an iodinated lipid emulsion. CT-quantification proved feasible post mortem and also in vivo, the latter enabling repeated therapy evaluation in the same animal. Post mortem quantification of hepatic metastases was also accomplished by computer-based area calculation (CBAC) on serial liver sections. The three evaluation procedures were in agreement for quantification of intermediate and extensive hepatic metastatic growth, but not for livers with small and few metastases. A similar CT evaluation technique, may also be possible for human application. Several pharmacokinetic aspects of RIL were evaluated, using the 125I-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) preparations I-38S1, AEC 38 and II-16. MAb AEC 38 was produced by additional purification of I-38S1 by anion exchange chromatography. Most MAb I-38S1, AEC 38 and II-16 accumulated in the s.c. xenografts during the first 24 h, the maximum being reached on days 2-4, depending on the MAb preparation used. The patterns of uptake and clearance of AEC 38, I-38S1 and II-16, found in gamma camera registrations, were in agreement with those of external detector measurements. Additional purification of I-38S1 by anion exchange chromatography improved the in vivo MAb uptake in s.c. xenografts, but its immunoreactivity in vitro was impaired by this procedure. The uptake of I-38S1 in hepatic metastases was not size dependent and was higher than in s.c. xenografts, irrespective of the mode of MAb injection (i.p. or i.v.). Uptake of I-38S1 in s.c. xenografts was independent on injection mode. By contrast, in liver metastases there was a marked tendency toward a higher uptake of I-38S1 following i.p. vis-a-vis i.v. antibody administration, although not statistically significant, possibly due to an apparent variability between animals and between different liver metastases in the same rat. This variability was not evident for s.c. xenografts.(ABSTRACT TRUNCATED AT 400 WORDS)
Sundin
A
A
Department of Diagnostic Radiology, Uppsala University, Sweden.
D000293:Adolescent; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D016009:Chi-Square Distribution; D003110:Colonic Neoplasms / Q000473:pathology*; D016001:Confidence Intervals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D008114:Liver Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000556:secondary*; D009368:Neoplasm Transplantation; D016719:Radioimmunodetection / Q000379:methods* / Q000706:statistics & numerical data; D051381:Rats; D011923:Rats, Nude; D012878:Skin Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000556:secondary*; D014057:Tomography, X-Ray Computed / Q000295:instrumentation / Q000379:methods; D014183:Transplantation, Heterologous
D007457:Iodine Radioisotopes