European Journal of Nuclear Medicine Vol. 29, No. 12, December 2002 Abstract. The combined use of anti-angiogenic therapy (AT) and radioimmunotherapy (RIT) may improve the therapeutic outcome in patients with cancer lesions. This hypothesis is based on the ability of AT to suppress tu- mour endothelial compartments and the direct action of RIT against tumour cells. We previously confirmed this hypothesis in an established subcutaneous xenograft model of colon cancer. The purpose of the current inves- tigation was to determine the benefit of this combination within a liver metastasis model, which mimics treatment of minimal disease in an adjuvant setting. Liver metas- tases were established in nude mice by intrasplenic inoc- ulation of LS180 colon cancer cells; following such in- oculation, metastases of <1 mm in diameter can be ob- served at 1 week and these lesions can attain a size of several millimetres at 2 weeks. Daily AT with 2-me- thoxyoestradiol (2-ME), 75 mg/kg, was initiated at 1 week. RIT with 7 MBq of 131 I-A7, an IgG1 anti-colorec- tal monoclonal antibody, was conducted at 2 weeks. RIT employing an irrelevant IgG1, 131 I-HPMS-1, was imple- mented for comparison. The weight of liver metastases was measured 4 weeks after cell inoculation. The effect of AT on 131 I-A7 accumulation in metastases was also observed. Toxicity of treatment was monitored by blood cell counts. Monotherapy with 2-ME AT or 131 I-A7 RIT significantly suppressed metastasis growth (P<0.0001): metastasis weight was 5.96±0.87 g in non-treated con- trols, 2.67±1.89 g in cases receiving AT and 0.85±0.68 g in those receiving 131 I-A7 RIT. Combination of AT and 131 I-A7 RIT more effectively suppressed the growth to 0.28±0.32 g (P<0.05 vs RIT alone). The effect of 131 I- HPMS-1 RIT, which suppressed metastasis growth to 2.25±0.88 g, was significant in comparison with the con- trol (P<0.0001); however, the combination of AT and 131 I-HPMS-1 RIT (which suppressed growth to 1.41±0.68 g) was far less effective than the combination of AT and 131 I-A7 RIT. AT did not decrease 131 I-A7 ac- cumulation in metastases. AT did not affect RIT myelo- toxicity. The results of this study demonstrating the com- bined effects of AT and 131 I-A7 RIT in a small metastasis model indicate that such combination therapy may be suitable for the treatment of minimal disease. Keywords: Radioimmunotherapy – Anti-angiogenic ther- apy – 2-Methoxyestradiol – Metastasis model Eur J Nucl Med (2002) 29:1669–1674 DOI 10.1007/s00259-002-0997-9 Introduction Radioimmunotherapy (RIT) employing radiolabelled monoclonal antibodies (MAb) against tumours has been extensively tested for two decades. However, in most cases the results have demonstrated limited success in bulky disease [1]. On the other hand, a number of re- ports have suggested a role for RIT as an adjuvant treat- ment of cancer [2, 3, 4, 5, 6, 7, 8]. Indeed, prolonged survival with RIT has been documented in patients pre- senting with minimal residual disease of ovarian cancer [9]. Seigo Kinuya ( ✉ ) Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan e-mail: kinuya@med.kanazawa-u.ac.jp Tel.: +81-76-2652333, Fax: +81-76-2344257 Original article Benefits of combined radioimmunotherapy and anti-angiogenic therapy in a liver metastasis model of human colon cancer cells Xiao-Feng Li 1 , Seigo Kinuya 1 , Kunihiko Yokoyama 1 , Kiyoshi Koshida 2 , Hirofumi Mori 3 , Kazuhiro Shiba 3 , Naoto Watanabe 4 , Noriyuki Shuke 5 , Takatoshi Michigishi 1 , Norihisa Tonami 1 1 Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan 2 Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan 3 Radioiosotope Center, Kanazawa University, Kanazawa, Japan 4 Department of Radiology, Toyama Medical and Pharmaceutical University, Toyama, Japan 5 Department of Radiology, Asahikawa Medical College, Asahikawa, Japan Received: 2 July 2002 / Accepted: 9 August 2002 / Published online: 2 October 2002 © Springer-Verlag 2002