Complete ablation of small squamous cell carcinoma xenografts with¹⁸⁶Re-labeled monoclonal antibody E48

Abstract

In previous studies we have shown that in mice bearing head and neck squamous cell carcinoma (HNSCC) xenografts, radioimmunotherapy (RIT) with¹⁸⁶Re-labeled MAb E48 resulted in complete regressions in one-third of the tumors (followup >150 d). MAb E48 was labeled with¹⁸⁶Re following a novel labeling procedure developed at our institute. The injected dose was 600 μCi, which was the maximum tolerated dose (MTD; <15% wt loss) in these studies. The mean size of the tumors was 140±60 mm³. To investigate whether the therapeutic efficacy of RIT in our xenograft model would be improved when treating smaller xenografts, mice bearing 2 HNSCC xenografts with a vol of 75±17 mm³ (number of mice,n=6; number of tumors,t=12) were treated with 600 μCi of¹⁸⁶Re-labeled MAb E48 IgG. All tumors completely regressed and did not regrow during followup (>150 d). In all mice, weight loss did not exceed 10%. to obtain biodistribution data, mice bearing two xenografts with a vol of 58±31 mm³ were injected with 100 μCi of¹⁸⁶Re-labeled MAb E48 IgG. The maximum uptake in blood was 26.4% injected dose/g (%ID·g⁻¹) at 2 h pi and was 53.1%ID·g⁻¹ in the tumor at d 7 pi. In normal tissues, no nonspecific accumulation was observed. Based on these biodistribution data, the absorbed cumulative radiation dose was calculated. The accumulated dose in blood and tumor was 2004 cGy and 8580 cGy, respectively. In other tissues, the dose was less than 8.1% of the dose delivered to tumor. These data implicate that RIT with¹⁸⁶Re-labeled MAb E48 may be especially suited to be used as adjuvant therapy for the treatment of head and neck cancer patients with minimal residual disease.