Can the Efficacy of [(18)F]FDG-PET/CT in Clinical Oncology Be Enhanced by Screening Biomolecular Profiles?

Positron Emission Tomography (PET) is a functional imaging modality widely used in clinical oncology. Over the years the sensitivity and specificity of PET has improved with the advent of specific radiotracers, increased technical accuracy of PET scanners and incremental experience of Radiologists. However, significant limitations exist—most notably false positives and false negatives. Additionally, the accuracy of PET varies between cancer types and in some cancers, is no longer considered a standard imaging modality. This review considers the relative influence of macroscopic tumour features such as size and morphology on 2-Deoxy-2-[(18)F]fluoroglucose ([(18)F]FDG) uptake by tumours which, though well described in the literature, lacks a comprehensive assessment of biomolecular features which may influence [(18)F]FDG uptake. The review aims to discuss the potential influence of individual molecular markers of glucose transport, glycolysis, hypoxia and angiogenesis in addition to the relationships between these key cellular processes and their influence on [(18)F]FDG uptake. Finally, the potential role for biomolecular profiling of individual tumours to predict positivity on PET imaging is discussed to enhance accuracy and clinical utility.