Brain tumor iron uptake measured with positron emission tomography and 52Fe-citrate

Iron and transferrin are required for DNA synthesis and cell division. Cellular iron uptake is mediated by transferrin receptors. In order to investigate whether iron uptake in brain tumors is associated with their histological grade, we studied 24 patients (5 astrocytoma, 11 glioblastoma, 8 meningioma) using positron emission tomography and 52Fe-citrate. Tracer uptake from blood into brain and tumor tissue was assessed 1. using multiple time graphical analysis yielding a measure for unidirectional net tracer uptake (Ki) and 2.) testing a one- and two-tissue kinetic compartment model, where K1 denotes tracer uptake from blood into tissue, k2 efflux from tissue into plasma, and k3 specific tracer binding. In the plasma, 52Fe was bound to a 80 kD protein (transferrin). Ki (in units of 10(-5)/min) was higher in glioblastomas (Ki mean +/- SD 13.6 +/- 6.1) compared with astrocytomas (4.8 +/- 3.5, Mann Whitney p = 0.015) and contralateral brain (2.2 +/- 0.9, Mann Whitney p = 0.009). Highest values were found in meningiomas (no blood-brain barrier (BBB); Ki 33.4 +/- 16.5, Mann Whitney p = 0.008 compared with glioblastomas). Among the compartment models, fitting with K1 and regional plasma volume explained the data best (one-tissue model), data fits were not significantly improved by addition of a k2 or k3 parameter. K1 and Ki values were significantly correlated (Spearman Rank, p = 0.0006). We conclude that 52Fe accumulation in tumors is governed by tracer uptake at the BBB, and does not reflect number of transferrin receptors at the level of tumor cells.