title: Mn-porphyrins as novel molecular magnetic resonance imaging contrast agents.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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: Department of Urology/Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors: Vladimir
authors: V
authors: Mouraviev
authors: Talaignair N
authors: TN
authors: Venkatraman
authors: Artak
authors: A
authors: Tovmasyan
authors: Masaki
authors: M
authors: Kimura
authors: Matvey
authors: M
authors: Tsivian
authors: Vladimira
authors: V
authors: Mouravieva
authors: Tom J
authors: TJ
authors: Polascik
authors: Haichen
authors: H
authors: Wang
authors: Timothy J
authors: TJ
authors: Amrhein
authors: Ines
authors: I
authors: Batinic-Haberle
authors: Christopher
authors: C
authors: Lascola
mesh_terms: D000818:Animals; D003287:Contrast Media; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008665:Metalloporphyrins; D019047:Phantoms, Imaging; D011471:Prostatic Neoplasms / Q000175:diagnosis*
chemical_list: D003287:Contrast Media; D008665:Metalloporphyrins; C520506:manganese tetrakis-(N-ethyl-2 pyridyl) porphyrin