**A Prospective Investigation of Tumor Hypoxia Imaging with 68Ga-Nitroimidazole PET/CT in Patients with Carcinoma of the Cervix Uteri and Comparison with 18F-FDG PET/CT: Correlation with Immunohistochemistry**

**Kgomotso M. G. Mokoala 1, Ismaheel O. Lawal 1,2, Letjie C. Maserumule 1, Khanyisile N. Hlongwa 1, Honest Ndlovu 1, Janet Reed 1, Meshack Bida 3, Alex Maes 1,4, Christophe van de Wiele 1,5, Johncy Mahapane 1, Cindy Davis 1, Jae Min Jeong 6,7, Gbenga Popoola 8, Mariza Vorster 1,2 and Mike M. Sathekge 1,2,\***


**Abstract:** Hypoxia in cervical cancer has been associated with a poor prognosis. Over the years 68Ga labelled nitroimidazoles have been studied and have shown improved kinetics. We present our initial experience of hypoxia Positron Emission Tomography (PET) imaging in cervical cancer with 68Ga-Nitroimidazole derivative and the correlation with 18F-FDG PET/CT and immunohistochemistry. Twenty women with cervical cancer underwent both 18F-FDG and 68Ga-Nitroimidazole PET/CT imaging. Dual-point imaging was performed for 68Ga-Nitroimidazole PET. Immunohistochemical analysis was performed with hypoxia inducible factor-1α (HIF-1α). We documented SUVmax, SUVmean of the primary lesions as well as tumor to muscle ratio (TMR), tumor to blood (TBR), metabolic tumor volume (MTV) and hypoxic tumor volume (HTV). There was no significant difference in the uptake of 68Ga-Nitroimidazole between early and delayed imaging. Twelve patients had uptake on 68Ga-Nitroimidazole PET. Ten patients demonstrated varying intensities of HIF-1α expression and six of these also had uptake on 68Ga-Nitroimidazole PET. We found a strong negative correlation between HTV and immunohistochemical staining (r = −0.660; *p* = 0.019). There was no correlation between uptake on PET imaging and immunohistochemical analysis with HIF-1α. Two-thirds of the patients demonstrated hypoxia on 68Ga-Nitroimidazole PET imaging.

**Keywords:** cervical cancer; hypoxia; 68Ga-Nitroimidazole; 18F-FDG; HIF-1α; immunohistochemistry
