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.