Complete ablation of small squamous cell carcinoma xenografts with 186Re-labeled monoclonal antibody E48.
In previous studies we have shown that in mice bearing head and neck squamous cell carcinoma (HNSCC) xenografts, radioimmunotherapy (RIT) with 186Re-labeled MAb E48 resulted in complete regressions in one-third of the tumors (followup > 150 d). MAb E48 was labeled with 186Re following a novel labeling procedure developed at our institute. The injected dose was 600 microCi, 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 microCi of 186Re-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 microCi of 186Re-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Gerretsen
M
M
Department of Otolaryngology/Head and Neck Surgery, Free University Hospital, Amsterdam, The Netherlands.
Visser
G W
GW
Brakenhoff
R H
RH
van Walsum
M
M
Snow
G B
GB
van Dongen
G A
GA
D000818:Animals; D000911:Antibodies, Monoclonal; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000627:therapeutic use*; D012211:Rhenium / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D012211:Rhenium