Hypoxia Imaging With the Novel Radiopharmaceutical 18F Fluoroazomycin Arabinoside (FAZA)- Prognostic Impact in Cervical Cancer

Introduction

Tumor hypoxia has been shown to be a prognostic factor for local progression and prognosis in several types of human cancers (1-4), including cervical carcinoma (5). Distribution of oxygen within a tumor can diminish toward the less vascularized center of the tumor (6, 7).

Hypoxia is an important factor in many pathological processes, including tumor formation, where it has been associated with resistance to radiotherapy, malignant progression, and metastasis. Although hypoxia is toxic to both cancer and normal cells, cancer cells undergo genetic and adaptive changes that allow them to survive and even proliferate within a hypoxic environment. These processes contribute to the malignant phenotype and to aggressive tumor behavior.

Hypoxia has a negative effect on anti cancer treatment (8). Radiotherapy is a major treatment modality for advanced cervical carcinomas and requires free radicals from oxygen to destroy target cells, and cells in hypoxic areas were found to be resistant to radiation-induced cell death (9). The gold standard for measuring hypoxia in tumors is the invasive technique of using computerized oxygen-sensitive electrodes. This method is cumbersome and expensive and has not become a general clinical tool for hypoxia measurement (10, 11).

Positron emission tomography (PET) becomes an interesting and promising diagnostic modality for hypoxia imaging in tumor tissue. Several tracers were developed for this purpose and Fluoromisonidazole (18FMISO) is the most extensively hypoxia tracer studied both in humans and animals (12-15). Previous results for imaging hypoxia using FMISO showed the regional distribution of tumor hypoxia, expressed as fractional hypoxic volume (16). However, its major disadvantages lie on its slow clearance kinetics and its high lipophilicity.