Carcinoembryonic antigen expression, antibody localisation and immunophotodetection of human colon cancer liver metastases in nude mice: A model for radioimmunotherapy

Abstract

2Division of Nuclear Medicine,Colorectal cancer frequently disseminates through the portal vein into the liver. In this study, outbred Swiss nude mice were adapted to facilitate the induction of liver metastases by a pre-grafting treatment with 6 Gy total body irradiation and i.v.injection of anti-asialo GM I antibody. One day later, cultured LS I74T human colon cancer cells were injected into the surgically exposed spleen, which was resected 3 min later. In 48 of 65 mice, a few to several hundred liver metastases were macroscopically observed at dissection 3 to 4 weeks after transplantation. Ten of I 0 mice, followed-up for survival, died with multiple large confluent liver metastases. By reducing the radiation dose to 4 or 0 Gy, or omitting the anti-asialo GM I antibody injection, only 60%. 37% or 50% of mice, respectively, had visible metastases 3 weeks after transplantation. Carcinoembryonic antigen (CEA) measured in tumour extracts was in the mean 25.6 pg/g in liver metastases compared with 9.2 pg/g in S.C. turnours. Uptake of radiolabelled anti-CEA monoclonal antibody (MAb) in the metastases 12, 24 and 48 hr after injection gave a mean value of 39% of the injected dose per gram of tissue (ID/g). In comparison, MAb uptake in S. C. and intrasplenic turnours or lung metastases gave a mean percentage ID/g of 20, I 8 and 15, respectively. Laser-induced fluorescence after injection of Indocyanin-MAb conjugate allowed direct visual detection of small liver metastases, including some that were not visible under normal light, Preliminary results showed that mice, pre-treated with 4 Gy irradiation and the anti-asialo GM I injection, were tolerant to radioimmunotherapy with a total dose of 500 pCi I 3 ' l labeled anti-CEA intact MAbs given in 3 injections.o 1996 Wiley-Liss, Inc.

Radioimmunotherapy for Liver Micrometastases in Mice: Pharmacokinetics, Dose Estimation, and Long‐term Effect

“…The histological analysis of the liver showed that the number and size of the metastases did indeed decrease with time after the injection of the therapeutic dose of 131 I-labeled F33-104, which was not observed after a tracer dose. In accord with the tracer studies, 4,18) the initial radioactivity uptake by the metastases was high and was maintained until day 6, but decreased thereafter. Despite the high radioactivity uptake by the metastases, the clearance of radioactivity from the blood was retarded and slower than that from the metastases.…”

“…14) Small lesions are thought to possess several properties favorable for RIT; 1) the radioactivity uptake by smaller lesions is higher and more homogeneous than that by larger lesions, [15][16][17][18] 2) the radiation dose necessary to control smaller lesions is expected to be significantly lower than that needed for larger lesions. 19) In the present investigation, the pharmacokinetics of a radiolabeled antibody in RIT were investigated to estimate the dose absorbed by the metastases.…”

Determination of tumor-related factors of influence on the uptake of the monoclonal antibody 323/A3 in experimental human ovarian cancer

“…A direct correlation between the accumulation of MAbs in melanoma xenografts and the density of a cell surface melanoma-associated glycoprotein has been reported by Shockley et al (1992b). Similarly, a positive relationship between CEA content in tumor tissue and uptake of anti-CEA MAbs has been observed in vivo (Vogel et al, 1996), although in other studies on anti-CEA MAbs no clear correlation was observed (Blumenthal et al, 1992;Folli et al, 1993).…”

Tumor Detection and Visualization Using Cyanine Fluorochrome-Labeled Antibodies

“…Cy5-conjugated monoclonal antibodies were used for in vivo tumor location by Folli et al (1994), Vogel et al (1996, and Ballou et al (1994Ballou et al ( , 1995aBallou et al ( ,b, 1996Ballou et al ( , 1997 using both mouse tumor models and human tumors xenografted in nude mice. Cyanineantibody conjugates proved to be both adequately stable and highly visible in vivo.…”