Forward to the Past: The Case for Quantitative PET Imaging.

PET was developed in the 1970s as an in vivo method to measure regional pathophysiologic processes. In the 1990s the focus moved to the detection of local increases in uptake, first in the brain (activation studies) and later in oncology (finding metastases), with 18F-FDG emerging as a highly sensitive staging technique. This focus on sensitivity has overshadowed the other main characteristic of PET, its quantitative nature. In recent years there has been a shift. PET is now seen as a promising tool for drug development and precision medicine-that is, a method to monitor or even predict response to therapy. Quantification is essential for precision medicine, but many studies today use simplified semiquantitative methods without properly validating them. This review provides several examples illustrating that simplified methods may lead to less accurate or even misleading results. Simplification is important for routine clinical practice, but finding the optimal balance between accuracy and simplicity requires careful studies. It is argued that the use of simplified approaches without proper validation not only may waste time and resources but also may raise ethical questions, especially in drug development studies.