Biology Reference
In-Depth Information
The diagnostic value of determining enzyme levels in patients has been
appreciated for years in clinical medicine and is the basis for a number of
simple and common serum blood tests. Included in these is the
determination of the serum serine protease known as prostate-specific anti-
gen and of creatine kinase for diagnosing prostate cancer and heart attack,
respectively. Although less specific for differential diagnosis, elevated serum
levels of aspartate aminotransferase (AST or SGOT), alanine aminotransfer-
ase (ALT or SGPT), alkaline phosphatase, 5 0 nucleotidase, and gamma-
glutamyl transpeptidase are routinely used as indicators of liver dysfunction.
Given the cost-effectiveness and almost universal availability of these assays,
the need for a method to anatomically localize and quantitate enzyme levels
in patients may not be readily apparent. However, in diseases such as cancer,
atherosclerosis, and infection, interventional procedures used for further
diagnosis (i.e., biopsy, exploratory surgery) and treatment (site-directed
radiation, tumor dissection, thrombectomy/embolectomy) can be accom-
plished with greater efficacy and safety when the exact location of diseased
tissue can be predetermined. Additionally, the choice of treatment may
depend on the extent of disease spread (such as metastatic tumors), in which
case an anatomical map of disease burden is extremely useful.
3. FLUORESCENCE DETECTION IN VIVO
Although more established clinical imaging modalities such as MRI
and PET have been applied to noninvasive detection of enzyme activity,
there is a growing interest in the use of fluorescence-based methods for this
purpose because of the inherent safety and cost-effectiveness of this imaging
modality. Fluorescence-based enzyme sensors are particularly attractive for
evaluating treatment effects after therapy, as the patient can be imaged mul-
tiple times without the fear of radiation-induced side effects. This is espe-
cially true, given the ever-growing number of therapeutics that target
enzyme activity. In addition, fluorescence-based methods are attractive be-
cause they offer the capacity to monitor multiple (in some cases up to 10)
targets (fluorescent molecules having different spectral parameters) simulta-
neously during the same exam/procedure. For these reasons, there has been
concerted effort in recent years to translate the wealth of knowledge gained
from the development of preclinical fluorescence-based imaging and to-
mography methods to the clinical arena. 35-37 Currently, indocyanine
green is the only near-infrared (NIR) fluorophore that has been approved
by the FDA for clinical use, and there are numerous studies that have
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