Validity of PET studies in brain tumors

Positron emission tomography (PET) in human brain tumors presents specific problems, such as tissue inhomogeneity and disruption of the blood-brain barrier (BBB), that are not present or at least not that important in normal brain. In addition, tracer metabolism may be different from normal brain. Mathematical arguments demonstrate that quantitation in inhomogeneous tissue is extremely difficult with tracers undergoing reversible metabolism, whereas irreversible metabolic steps can be quantified more easily. Even for metabolically inert tracers with reversible transport across the BBB, physiological identification of transport rate constants may be ambiguous, since diffusion processes within the tissue cannot be differentiated from slow transport components at the BBB. Mathematical analysis shows that transport is usually underestimated, whereas metabolism is usually overestimated in inhomogeneous tumor tissue. For accurate measurements of blood flow and BBB permeability, use of short measurement times is recommended. Measurements of tumor glucose consumption with [18F]2-fluoro-2-deoxy-D-glucose (FDG) are probably only little affected by tumor heterogeneity. There are, however, major problems caused by variation of the lumped constant, which relates the kinetics of FDG to those of glucose. Most experimental data indicate a considerable increase of the lumped constant in malignant tumors, resulting in overestimation of glucose metabolism if the standard value is used. In spite of these limitations, measurements of glucose metabolism with FDG are useful clinically to evaluate the prognosis of patients with brain tumors and to differentiate between late radiation necrosis and recurrent tumor. New tracers for measurement of protein synthesis, cell proliferation, and uptake of cytostatic drugs are of high clinical interest. As yet, little is known about the contribution of metabolites in brain and plasma to measured tissue activity, and differentiation between transport at the BBB and metabolism may be difficult. Therefore, the basis for accurate quantitation with these new compounds is still incomplete. Clinical reports suggest that some amino acid tracers can be used for localization and grading of brain tumors.