Radionuclide imaging of hypoxia: Where are we now? Special attention to cancer of the cervix uteri.

Cancer of the cervix is the fourth commonest malignancy in women worldwide and it also ranks fourth as the cause of cancer related mortality in women. Hypoxia is a common characteristic of solid tumours and cervical cancer is no exception. Hypoxia is associated with increased aggressiveness, risk of invasion and metastasis. Tumour hypoxia also results in resistance to both radiation therapy and chemotherapy leading to a poorer prognosis. In-vivo measurement of tumour hypoxia is vital in oncologic practice because it can predict outcome and identify patients with a worse prognosis. Mapping of tumour hypoxia may also help select patients that may benefit from applicable treatments. While traditional methods of measuring hypoxia such as the Eppendorf probe is considered the gold standard, it is invasive and technically demanding. Non-invasive methods of measuring tumourhypoxia are ideal. Positron emission tomography/computed tomography (PET/CT) imaging with nitro-imidazole-based tracers is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of hypoxia. Over the years various hypoxia specific PET tracers have been investigated in various malignancies including cancer of the cervix. Several fluorine-18 (18F)-based tracers have been studied and although most had small patient numbers, the results are promising and generally demonstrate an associate between the presence of hypoxia and treatment outcome. The need for an onsite cyclotron and specialized radiopharmacy skills make these tracers unattractive and largely unavailable for routine clinical applications. With the increase in availability of the gallium-68 (68Ga) generator this makes the 68Ga-labelled nitroimidazole derivatives attractive because 68Ga is available from a generator with a shelf life of almost a year. The chemistry of 68Ga makes for easy labelling with several peptides and molecules. Pre-clinical work has demonstrated the feasibility of using these tracers for imaging hypoxia and has laid the groundwork for further human studies with these tracers.The aim of this review is to discuss hypoxia and its impact in cancer of the cervix as well as to look into the progress made in hypoxia imaging in cancer of the cervix. This will focus on the tracers studied thus far and some of the challenges of hypoxia imaging.