BACKGROUND AND PURPOSE: In this study, we investigated the potential of a new class of therapeutic Mn porphyrins as molecular MRI probes for prostate cancer imaging. Two compounds of different bioavailibility were investigated: Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)) and Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5+)). These compounds have previously been shown to have adjunctive antineoplastic activity through their actions as powerful superoxide dismutase mimics, peroxynitrite scavengers, and modulators of cellular redox-based signaling pathways. Strong paramagnetic MRI contrast properties and affinity for cancer cells suggest their potential application as novel diagnostic imaging agents. MATERIALS AND METHODS: MRI experiments were performed at 7.0T on a Bruker Biospec horizontal bore scanner. All in-vivo experiments were performed on 12 C57 black mice implanted with RM-9 prostate cancer cells on the hind limb. Two mg/kg of MnTnHex-2-PyP(5+) (n=6) and 8 mg/kg MnTE-2-PyP(5+) (n=6) were administered intraperitoneally 90 minutes before imaging. All the images were collected using a volume coil and processed using Paravision 4.0. RESULTS: Phantom studies reveal remarkably high T1 relaxivity changes for both metalloporphyrins, which are twofold to threefold higher than commercially available gadolinium chelates. Observable detection limits using conventional T1-weighted MRI are in the low micromolar range for both compounds. In vivo, MR relaxation changes in prostate tumor xenografts were readily observed after a single injection of either MnTE-2-PyP(5+)or MnTnHex-2-PyP(5+), with tumor contrast to background ratio greatest after MnTE-2-PyP(5+) administration. CONCLUSION: After a single dose of MnTE-2-PyP(5+), contrast changes in prostate tumors are up to sixfold greater than in surrounding, noncancerous tissues, suggesting the potential use of this metalloporphyrin as a novel diagnostic probe for detecting prostate malignancy using MRI.
BACKGROUND AND PURPOSE: In this study, we investigated the potential of a new class of therapeutic Mn porphyrins as molecular MRI probes for prostate cancer imaging. Two compounds of different bioavailibility were investigated: Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)) and Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5+)). These compounds have previously been shown to have adjunctive antineoplastic activity through their actions as powerful superoxide dismutase mimics, peroxynitrite scavengers, and modulators of cellular redox-based signaling pathways. Strong paramagnetic MRI contrast properties and affinity for cancer cells suggest their potential application as novel diagnostic imaging agents. MATERIALS AND METHODS: MRI experiments were performed at 7.0T on a Bruker Biospec horizontal bore scanner. All in-vivo experiments were performed on 12 C57 black mice implanted with RM-9 prostate cancer cells on the hind limb. Two mg/kg of MnTnHex-2-PyP(5+) (n=6) and 8 mg/kg MnTE-2-PyP(5+) (n=6) were administered intraperitoneally 90 minutes before imaging. All the images were collected using a volume coil and processed using Paravision 4.0. RESULTS: Phantom studies reveal remarkably high T1 relaxivity changes for both metalloporphyrins, which are twofold to threefold higher than commercially available gadolinium chelates. Observable detection limits using conventional T1-weighted MRI are in the low micromolar range for both compounds. In vivo, MR relaxation changes in prostate tumor xenografts were readily observed after a single injection of either MnTE-2-PyP(5+)or MnTnHex-2-PyP(5+), with tumor contrast to background ratio greatest after MnTE-2-PyP(5+) administration. CONCLUSION: After a single dose of MnTE-2-PyP(5+), contrast changes in prostate tumors are up to sixfold greater than in surrounding, noncancerous tissues, suggesting the potential use of this metalloporphyrin as a novel diagnostic probe for detecting prostate malignancy using MRI.
Authors: Ines Batinic-Haberle; Zrinka Rajic; Artak Tovmasyan; Julio S Reboucas; Xiaodong Ye; Kam W Leong; Mark W Dewhirst; Zeljko Vujaskovic; Ludmil Benov; Ivan Spasojevic Journal: Free Radic Biol Med Date: 2011-05-06 Impact factor: 7.376
Authors: Huaxin Sheng; Ivan Spasojevic; Hubert M Tse; Jin Yong Jung; Jun Hong; Zhiquan Zhang; Jon D Piganelli; Ines Batinic-Haberle; David S Warner Journal: J Pharmacol Exp Ther Date: 2011-06-07 Impact factor: 4.030
Authors: Xiaodong Ye; Diane Fels; Artak Tovmasyan; Katherine M Aird; Casey Dedeugd; Jennifer L Allensworth; Ivan Kos; Won Park; Ivan Spasojevic; Gayathri R Devi; Mark W Dewhirst; Kam W Leong; Ines Batinic-Haberle Journal: Free Radic Res Date: 2011-09-27
Authors: Ivan Spasojevic; Ivan Kos; Ludmil T Benov; Zrinka Rajic; Diane Fels; Casey Dedeugd; Xiaodong Ye; Zeljko Vujaskovic; Julio S Reboucas; Kam W Leong; Mark W Dewhirst; Ines Batinic-Haberle Journal: Free Radic Res Date: 2010-10-13
Authors: Artak Tovmasyan; Romulo S Sampaio; Mary-Keara Boss; Jacqueline C Bueno-Janice; Bader H Bader; Milini Thomas; Julio S Reboucas; Michael Orr; Joshua D Chandler; Young-Mi Go; Dean P Jones; Talaignair N Venkatraman; Sinisa Haberle; Natalia Kyui; Christopher D Lascola; Mark W Dewhirst; Ivan Spasojevic; Ludmil Benov; Ines Batinic-Haberle Journal: Free Radic Biol Med Date: 2015-10-20 Impact factor: 7.376