Biology Reference
In-Depth Information
and the rate of fluorophore liberation by the enzyme can be rewritten as
d
L
d
T
¼
acD
t
,
½
9
:
3
where
D
t
is the concentration of the sensor in the target organ at any mo-
ment of time,
c
is the dimensionless concentration of the fluorophore in the
carrier macromolecule, and
a
is the proportionality coefficient.
Thus, in the presence of nonzero blood flow
J
v
through the target organ,
in general, extravascular fluorescence intensity measured in the target organ
can be expressed as
I
o
I
e
¼
AD
T
c
,
½
9
:
4
where
D
T
can be calculated using the initial known i.v. injected dose of the
macromolecular imaging sensor
D
o
:
D
T
¼
D
o
1
ð
exp
ð
Bt
Þ
Þ
,
PSJ
v
V
e
K
av
B
¼
and
where
PS
is the permeability-surface product of vasculature through which
the macromolecular carrier is being transported,
J
v
is the blood flow rate,
V
e
is the extravascular volume, and
K
av
is the available volume fraction in the
extravascular compartment. Some of the above parameters can be estimated
experimentally using intravital microscopy and whole-body optical
imaging.
103,104
It should be noted that, in general, the kinetics of fluorescent product
release or formation is nonlinear and Eq.
(9.3)
is written in a simplified form.
Equation
(9.3)
, which affects Eq.
(9.4)
, ideally has to reflect the order of
enzymatic reaction, which unfortunately is unknown for many lysosomal
hydrolases and other enzymes that are involved in proteolysis of “quenched”
macromolecular carriers of fluorophores in the extracellular matrix.
7. APPLICATIONS OF MACROMOLECULAR
FLUORESCENT SENSORS IN CANCER IMAGING
The potential for optical imaging of disease-related enzyme activation
has been most widely studied in animal models of cancer. The events that
take place at the interface between proliferating tumor and surrounding tis-
sue, that is, tumor progression, stromal cell activation, tissue invasion, and
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