Selective and prolonged MRI enhancement by Mn-TPPS in an experimental rat brain tumour with peripheral benzodiazepine receptors.
Synthesized Mn-TPPS, a paramagnetic metalloporphyrin, is expected to be a tumour specific contrast media for magnetic resonance (MR) imaging. We investigated the enhancing characteristics of Mn-TPPS using a transplanted rat C6 glioma model with peripheral type benzodiazepine (PBD) receptors since porphyrins are thought to possibly be endogenous ligands for PBD receptors. An Mn-TPPS enhancement study was then performed either with or without pretreatment while using peripheral and central type benzodiazepine receptor specific ligands (PK11195 and clonazepam, 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, was not inhibited nor replaced by benzodiazepines. The tissue concentration of Mn-TPPS was significantly higher in the glioma tissue than the other tissues, while PK11195 pretreatment could not reduce the intratumoural Mn-TPPS concentration. A subcellular distribution study disclosed that Mn-TPPS was readily incorporated into the tumour cells. On the other hand, Mn-TPPS was not specifically distributed in the mitochondrial fraction where PBD receptors exist. The present study therefore indicates that Mn-TPPS could be incorporated into tumour cells and supports the potential use of this agent to improve the diagnostic specificity of MR imaging for brain tumours.
Ikezaki
K
K
Department of Neurosurgery, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Nomura
T
T
Takahashi
M
M
Fritz-Zieroth
B
B
Inamura
T
T
Fukui
M
M
D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D002998:Clonazepam / Q000378:metabolism; D003287:Contrast Media; D005910:Glioma / Q000175:diagnosis*; D007546:Isoquinolines / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011166:Porphyrins / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000032:analysis* / Q000378:metabolism; D014018:Tissue Distribution
D003287:Contrast Media; D007546:Isoquinolines; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D011963:Receptors, GABA-A; C016136:tetraphenylporphine sulfonate; D002998:Clonazepam; C037850:PK 11195