Abstract 439: Evaluation of hypoxia in a feline model of head and neck squamous cell carcinoma using 64Cu-ATSM positron emission tomography

Abstract

Abstract Tumor hypoxia substantially impacts the prognosis of cancer patients by impairing the response to therapy and by promoting the acquisition of a malignant cellular phenotype. A variety human tumors exhibit hypoxia including head and neck squamous cell carcinoma (HNSCC) where it is considered a barrier to successful management of these patients. In the feline, HNSCC is a common and aggressive malignancy that shares morphologic, clinical and molecular features with human HNSCC. Therefore, feline HNSCC may serve as an informative model. To date, there are no data concerning the occurrence of hypoxia in feline HNSCC. We hypothesized that like its human counter part, feline HNSCC would demonstrate regions of intratumoral hypoxia and that hypoxia would be a feature of malignant rather than benign oral tumors. To test this hypothesis, cats with spontaneously occurring oral tumors (N=7) were administered 2 mCi 64Cu- diacetyl-bis(N4-methylthiosemicarbazone) (ATSM) IV 20 minutes prior to PET-CT scan (Discovery ST, GE Healthcare). Histologically, 4 cats had invasive squamous cell carcinoma, 1 had osteosarcoma and 2 had inflammatory lesions (1 polyp and 1 granuloma). All four squamous cell carcinomas and both inflammatory lesions demonstrated strong diffuse uptake of 64Cu within the tumor. Two cats with metastases to regional lymph nodes also demonstrated significant 64Cu uptake. Tumor hypoxia was confirmed by fluorescent lifetime probe measurements (Oxylab pO2), Oxford Optronix) in 4 cats and pimonidazole (HypoxyporbeTM-1, Hypoxyprobe Inc) uptake in biopsy samples in 4 cats. These data indicate that HNSCC in the cat exhibits significant, diffuse hypoxia. Hypoxia was also significant in inflammatory lesions and thus was not a marker of malignancy, but could indicate that inflammatory disease may provide a selective microenvironement to promote tumorigenesis in the cat. The feline model may provide an important tool for studying clinical methods to modulate hypoxia and to study the role of hypoxia on oral carcinogenesis. We are currently evaluating the effect of vascular modulating agents on feline HNSCC and intratumoral hypoxia as a means to optimize this therapy for combination with irradiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 439.