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Published on: April 28, 2015
Mn-porphyrins as novel molecular magnetic resonance imaging contrast agents
Vladimir Mouraviev1, Talaignair N Venkatraman, Artak Tovmasyan
1Department of Urology/Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
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.
Insights
Manganese porphyrins show promise as MRI contrast agents for prostate cancer. MnTE-2-PyP(5+) enhanced tumor visibility sixfold, suggesting its potential for early cancer detection.
Area of Science:
- Biomedical Imaging
- Materials Science
- Oncology
Background:
- Investigated novel manganese (Mn) porphyrins as potential molecular MRI probes for prostate cancer.
- Two Mn porphyrin compounds, MnTE-2-PyP(5+) and MnTnHex-2-PyP(5+), with varying bioavailability were studied.
- These compounds exhibit antioxidant and anti-cancer properties, and possess paramagnetic MRI contrast capabilities.
Purpose of the Study:
- To evaluate the efficacy of Mn porphyrins as diagnostic imaging agents for prostate cancer.
- To assess their potential as molecular MRI probes for enhanced cancer detection.
Main Methods:
- In vivo MRI experiments conducted at 7.0T on C57 black mice bearing RM-9 prostate cancer xenografts.
- Administration of MnTnHex-2-PyP(5+) (2 mg/kg) and MnTE-2-PyP(5+) (8 mg/kg) intraperitoneally 90 minutes prior to imaging.
- Image acquisition using a volume coil and processed with Paravision 4.0 software.
Main Results:
- Phantom studies demonstrated significantly higher T1 relaxivity for both Mn porphyrins compared to gadolinium chelates.
- Detection limits in the low micromolar range were achieved using conventional T1-weighted MRI.
- In vivo imaging revealed observable MR relaxation changes in prostate tumors after a single injection of either compound, with MnTE-2-PyP(5+) yielding the highest tumor-to-background contrast.
Conclusions:
- MnTE-2-PyP(5+) demonstrated up to sixfold greater contrast changes in prostate tumors compared to surrounding non-cancerous tissues.
- These findings suggest MnTE-2-PyP(5+) holds significant potential as a novel diagnostic MRI probe for detecting prostate malignancy.
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