Chemistry Reference
In-Depth Information
basic pH values. The reduction/dissolution processes operated by suitable reducing agents lead to hundreds of
apoferritin system shows markedly
e
FIGURE 22.15
Mn
e
Apoferritin preparation.
(From Kalman et al., 2010. Copyright 2010 with permission from John Wiley and Sons.)
superior properties as an MRI contrast agent, as its relaxivity per apoferritin particle is almost one order of
magnitude higher than that shown by Gd-loaded apoferritin due to accumulation of a large number of manganese
ions in its inner cavity.
While the first generation of MRI contrast agents are relatively unspecific, they nonetheless allow the
evaluation of physiological parameters such as the status of the blood
brain barrier or renal function. Gd-
DTPA-enhanced MRI imaging can assist in the diagnosis and treatment follow-up of many types of cancer.
However, in order to improve the diagnostic efficacy of contrast agents, they need to be made target specific so
that they accumulate in specific biological locations. Approaches which have been tried include coupling
contrast agents to antibodies against membrane receptors, to transferrin in order to image tumour cells, which
overexpress the transferrin receptor, or to annexin V, a protein which binds to phosphatidylserine, as a marker
of apoptosis. Phosphatidylserine moves from the interior to the exterior of cell membranes when a cell
undergoes apoptosis. Several “smart” sensor probes have been designed which are activated only in the
presence of their intended target. As one example, a gadolinium-based smart contrast agent has been
developed to demonstrate gene transfection (
Figure 22.16
). When the enzyme
e
b
-galactosidase is expressed in
FIGURE 22.16
Enzyme-activated MR contrast agent. Schematic of the transition of methyl substituted Egad (EgadMe) from a weak to
a strong relaxivity state. This diagram represents the site-specific placement of the galactopyranosyl ring on the tetraazamacro-cycle (side
view). Upon cleavage of the sugar residue by
b
-galactosidase, an inner sphere coordination site of the Gd
3
þ
ion becomes more accessible to
water.
(From
Meade, Taylor, & Bull, 2003
. Copyright 2003 with permission from Elsevier.)
