Imaging pharmacodynamics in oncology: the potential significance of "flares"

The clinical use of (18)F-fluorodeoxyglucose (FDG) positron emission tomography in monitoring anticancer treatment is expanding. At the same time a number of radiotracers aiming to image different aspects of tumour biology such as proliferation and apoptosis are being developed. However, the factors determining changes of radiotracer uptake parameters in response to treatment are not well understood. In many cases, cellularity may be the primary determinant of changes of FDG uptake and may confound the interpretation of metabolic changes. Early imaging assessments have in some cases showed transient increases of uptake parameters, commonly termed "flares", which are likely to be unaffected by cellularity and directly reflect pharmacodynamics at a cellular level. In this review a number of settings where molecular imaging "flares" have been described are discussed. Such changes may often be clinically informative and warrant careful study as potential predictive biomarkers.