Science / Technology - Colloquium
Monday, April 6, 2009
4:00 PM-5:00 PM
Olin Hall
107
Although most manganese-enhanced MRI (MEMRI) methods employ Mn2+ as a Ca2+ analogue, other mechanisms for delivering manganese into cells and tissue are also possible. For example, transferrins (Tf) a major class of plasma iron-binding proteins can accommodate a variety of other metal ions (including manganese) in the two available iron-binding domains of the Tf molecule. In particular, Tf has been shown to be one of the major manganese plasma-transport proteins for both rodents and humans in the form of Mn(III)-Tf.
Metal-Tf transport is initiated when the metalloprotein binds to transferrin receptor 1 (TfR1) at the cell surface. The metal-Tf/TfR1 complex is then transported into the cell via TfR1-mediated endocytosis. The acidic pH (~5.5) that develops within the resulting endosomal compartment releases the metal from the internalized protein complex. The free manganese is then reduced and transported across the endosomal membrane into the cytosol; where it can function as an effective MRI contrast agent. The metal-free apo-Tf/TfR1 complex is recycled back to the cell surface, where both proteins are reused in another cycle of cellular metal-ion uptake. The cyclical nature of this process can potentially label cells with relatively high concentrations of manganese.
TfR1-mediated endocytosis has been investigated as a novel approach for manganese cell labeling and tissue delivery using Mn(III)-Tf. The degree of manganese cell labeling following incubation of murine hepatocytes for 2-7 h in 31.5 M Mn(III)-Tf was comparable to that of hepatocytes incubated in 500 M Mn2+ for 1 h. Manganese delivery and transport has also been investigated in vivo following direct intracerebral injection of Mn(III)-Tf into the rat brain. Intracerebral infusions of from 5-20 L of ~1 mM Mn(III)-Tf resulted in significant T1-relaxation-time enhancement; comparable to that observed following direct injection of Mn2+ alone at the same concentration. Furthermore, the subsequent transport of manganese along neuronal tracts originating from the injection site provides further evidence for the in vivo cellular delivery of Mn2+ via TfR1-mediated endocytosis. This approach represents a novel way to use a biological pathway for targeting and to release an MRI contrast agent into cells.
Cost: FREE
Suggested Audiences: Adult
E-mail:
izabela@wpi.edu
Phone: 508-831-5249
Last Modified: April 6, 2009 at 8:33 AM
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