Mn-porphyrins as novel molecular magnetic resonance imaging contrast agents.
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) mesotetrakis(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.
Mouraviev, V; Venkatraman, TN; Tovmasyan, A; Kimura, M; Tsivian, M; Mouravieva, V; Polascik, TJ; Wang, H; Amrhein, TJ; Batinic-Haberle, I; Lascola, C
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