Individualized Treatment Planning in Oncology: Role of PET and Radiolabelled Anticancer Drugs in Predicting Tumour Resistance

Tumour resistance to anticancer agents remains a challenge in oncological practice, because it results in exposure to toxicities, unnecessary costs and, most importantly, delay of a potentially more effective treatment. Drug uptake by tumours may be impaired by several resistance pathways. Reasons for primary resistance may be that the drug is not delivered to the tumour or that its uptake by the tumour is not sufficient. Drug delivery depends on its distribution within the body, its bioavailability in the circulation and its transport to the tumour. Binding of drugs to circulating cells and proteins, formation of inactive metabolites as well as a rapid drug clearance may limit bioavailability. Furthermore, drug delivery to tumours is regulated by tumour vascularisation. Finally, tumour targets such as hormone receptors and efflux pumps also influence drug uptake by tumours. The use of specific PET tracers such as radiolabelled anticancer drugs (e.g. [¹⁸F]fluoropaclitaxel and [¹⁸F]5-fluorouracil) provide a unique means for individualized treatment planning and drug development. Combining these specific tracers with other less specific tracers, such as tracers for blood flow (e.g. [¹⁵O]H2O) and efflux (e.g. [¹¹C]verapamil), may provide additional information on drug resistance mechanisms. Furthermore, radiolabelled anticancer agents may be valuable to evaluate the optimal timing of combination therapies. This review will focus on how PET can reveal different mechanisms of tumour resistance and thus may play a role in drug development and prediction of tumour response.