BACKGROUND: Tetraiodothyroacetic acid (tetrac) is a deaminated analogue of 
L-thyroxine that blocks the actions of L-thyroxine and 
3,5,3'-triiodo-L-thyronine at the cell surface receptor for thyroid hormone on 
integrin alpha v beta 3. Tetrac blocks the proliferative effects of thyroid 
hormone on tumor cells and the proangiogenesis actions of the hormone. In the 
absence of thyroid hormone, tetrac also blocks angiogenesis induced by various 
growth factors. Covalently linked to poly(lactide-co-glycolide), tetrac 
nanoparticles (tetrac NP) do not gain access to the cell interior and act 
exclusively at the integrin receptor. Here, the activity of tetrac and tetrac NP 
against follicular thyroid carcinoma (FTC)-236 cells was studied in two models: 
(1) tumor cell implants in the chick chorioallantoic membrane (CAM) system and 
(2) xenografts in the nude mouse.
METHODS: FTC-236 cells (10(6)) were implanted in the CAM (n = 8 each for 
control, and for tetrac and tetrac NP, both at 1 microg/CAM) and the actions of 
tetrac and tetrac NP were determined after 8 days on tumor-related angiogenesis 
and tumor growth. Xenografts of 10(7) FTC-236 cells were implanted in nude mice 
(n = 8 per group). Tetrac or tetrac NP was administered intraperitoneal (1 mg/kg 
and 1 mg tetrac equivalent/kg, respectively) every other day for 32 days 
beginning on day 10, when tumor volume was 200-250 mm(3). Animals were monitored 
after discontinuation of treatment up to day 40.
RESULTS: In the CAM paradigm, tetrac and tetrac NP arrested tumor-related 
angiogenesis and tumor growth. In the xenograft model, tetrac and tetrac NP 
promptly and progressively reduced tumor volume (p < 0.01) over 32 days. There 
was some regrowth of tumor after interruption of tetrac treatment, but at day 
40, tumor volume and tumor weight at sacrifice were 45-55% below those of 
controls (p < 0.01). Animal weight gain was comparable in the control and 
treatment groups of animals.
CONCLUSIONS: Tetrac and tetrac NP effectively arrest FTC-236 cell tumor growth 
in the CAM and xenograft models, suggesting its potential utility against FTC.