Role of PET quantitation in the monitoring of cancer response to treatment: Review of approaches and human clinical trials

Positron emission tomography (PET) measures of cancer metabolism and cellular proliferation are increasingly being studied as markers of cancer response to treatment, with the goal of using them as predictors of patient therapeutic outcomes - i.e., as surrogate outcome measures. The primary PET radiotracers thus far used for monitoring response of cancer to treatment are ¹⁸F-fluorodeoxyglucose (FDG) for studying abnormal energy metabolism and ¹⁸F-fluorothymidine (FLT) for examining cell proliferation. Both FDG and FLT PET quantitation of cancer response to treatment have been found to correlate with patient outcomes, mostly in single-center studies. The aim of this review is to summarize the impact of commonly selected PET quantitation methods on the ability of PET measures to quantitate cancer response to treatment. An understanding of the biochemistry and kinetics of FDG and FLT uptake and knowledge of the expected tracer uptake by cancerous processes relative to background uptake are required to select appropriate PET quantitation methods for trials testing for correlations between PET measures and patient outcome. PET measures may eventually serve as predictive biomarkers capable of guiding individualized treatment and improving patient outcomes and quality of life by early identification of ineffective therapies. PET can also potentially identify patients who would be good candidates for molecularly targeted drugs and monitor response to these personalized therapies.