SELECTIVE AND PROLONGED MRI ENHANCEMENT BY MN-TPPS IN AN EXPERIMENTALRAT-BRAIN TUMOR WITH PERIPHERAL BENZODIAZEPINE RECEPTORS

Synthesized Mn-TPPS, a paramagnetic metalloporphyrin, is expected to b e a tumour specific contrast media for magnetic resonance (MR) imaging . We investigated the enhancing characteristics of Mn-TPPS using a tra nsplanted rat C6 glioma model with peripheral type benzodiazepine (PBD ) receptors since porphyrins are thought to possibly be endogenous lig ands for PBD receptors. An Mn-TPPS enhancement study was then performe d either with or without pretreatment while using peripheral and centr al type benzodiazepine receptor specific ligands (PK11195 and clonazep am, respectively). A signal intensity analysis disclosed the selective and prolonged enhancement of the brain tumour even at 17 h after the Mn-TPPS injection. This specific enhancement of the tumour, however, w as not inhibited nor replaced by benzodiazepines. The tissue concentra tion of Mn-TPPS was significantly higher in the glioma tissue than the other tissues, while PK11195 petreatment could not reduce the intratu moural Mn-TPPS concentration. A subcellular distribution study disclos ed that Mn-TPPS was readily incorporated into the tumour cells. On the other hand, Mn-TPPS was not specifically distributed in the mitochond rial fraction where PBD receptors exist. The present study therefore i ndicates that Mn-TPPS could be incorporated into tumour cells and supp orts the potential use of this agent to improve the diagnostic specifi city of MR imaging for brain tumours.