BRAIN-TUMOR IRON UPTAKE MEASURED WITH POSITRON EMISSION TOMOGRAPHY AND FE-52-CITRATE

Iron and transferrin are required for DNA synthesis and cell division. Cellular iron uptake is mediated by transferrin receptors. In order t o investigate whether iron uptake in brain tumors is associated with t heir histological grade, we studied 24 patients (5 astrocytoma, 11 gli oblastoma, 8 meningioma) using positron emission tomography and Fe-52- citrate. Tracer uptake from blood into brain and tumor tissue was asse ssed 1. using multiple time graphical analysis yielding a measure for unidirectional net tracer uptake (Ki) and 2.) testing a one- and two-t issue kinetic compartment model, where K1 denotes tracer uptake from b lood into tissue, k2 efflux from tissue into plasma, and k3 specific t racer binding. In the plasma, Fe-52 was bound to a 80 kD protein (tran sferrin). Ki (in units of 10(5)/min) was higher in glioblastomas (Ki m ean +/- 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 regi onal plasma volume explained the data best (one-tissue model), data fi ts 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 Fe-52 accumulation in tumors is governed by t racer uptake at the BBB, and does not reflect number of transferrin re ceptors at the level of tumor cells.