Molecular cardiovascular imaging.
ABSTRACT Imaging with radionuclides has historically played an important role in detection of cardiovascular disease as well as in risk stratification and prognostication. With the growth of molecular biology have come new therapeutic interventions and the requirement for new diagnostic imaging approaches. Noninvasive targeted radiotracer-based strategies require the development of new instrumentation to meet these needs. This progress has been made possible with the availability of many technologic advances, which include dedicated micro single-photon emission computed tomography (SPECT) and micro positron emission tomography (PET) hybrid systems for small animal imaging. This review is a brief overview on the subject of molecular imaging. Basic concepts of molecular imaging are reviewed, followed by description of current technologic advances, and current applications to evaluate ischemic heart disease and potential therapeutic intervention. The emphasis is on the use of both SPECT and PET radiotracers, although other imaging modalities are also briefly discussed.
- [show abstract] [hide abstract]
ABSTRACT: Noninvasive methods for characterizing neovessel formation during angiogenesis are currently lacking. We hypothesized that angiogenesis could be imaged with the use of contrast-enhanced ultrasound (CEU) with microbubbles targeted to alpha(v)-integrins. Microbubbles targeted to alpha(v)-integrins were prepared by conjugating echistatin (MB(E)) or monoclonal antibody against murine alpha(v) (MB(alpha)) to their surface. Control microbubbles (MB(c)) were also prepared. The microvascular behavior of these microbubbles was assessed by intravital microscopy of the cremaster muscle in mice treated for 4 days with sustained-release FGF-2. Microvascular retention was much greater (P<0.01) for MB(E) (11+/-6 mm(-3)) and MB(alpha) (10+/-7 mm(-3)) than that for MB(c) (1+/-1 mm(-3)). Retained MB(E) and MB(alpha) attached directly to the microvascular endothelial surface. Microbubble retention in 4 control mice was minimal. Subcutaneous matrigel plugs enriched with FGF-2 were created in 12 mice and studied 10 days later. Neovessels within the matrigel stained positive for alpha(v)-integrins. CEU demonstrated greater (P<0.01) acoustic intensity for MB(E) (16.0+/-5.9 U) and MB(alpha) (17.0+/-5.5 U) compared with MB(c) (5.8+/-2.6 U). The signal from targeted microbubbles (MB(E) and MB(alpha)) correlated well (r=0.90) with the matrigel blood volume determined by CEU perfusion imaging. CEU with microbubbles targeted for alpha(v)-integrins may provide a noninvasive method for assessing therapeutic angiogenesis.Circulation 01/2003; 107(3):455-60. · 15.20 Impact Factor
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ABSTRACT: The assessment of myocardial viability has become an important aspect of the diagnostic and prognostic work-up of patients with ischemic cardiomyopathy. Although revascularization may be considered in patients with extensive viable myocardium, patients with predominantly scar tissue should be treated medically or evaluated for heart transplantation. Among the many viability tests, noninvasive assessment of cardiac glucose use (as a marker of viable tissue) with F18-fluorodeoxyglucose (FDG) is considered the most accurate technique to detect viable myocardium. Cardiac FDG uptake has traditionally been imaged with positron emission tomography (PET). Clinical studies have shown that FDG-PET can accurately identify patients with viable myocardium that are likely to benefit from revascularization procedures, in terms of improvement of left ventricular (LV) function, alleviation of heart failure symptoms, and improvement of long-term prognosis. However, the restricted availability of PET equipment cannot meet the increasing demand for viability studies. As a consequence, much effort has been invested over the past years in the development of 511-keV collimators, enabling FDG imaging with single-photon emission computed tomography (SPECT). Because SPECT cameras are widely available, this approach may allow a more widespread use of FDG for the assessment of myocardial viability. Initial studies have directly compared FDG-SPECT with FDG-PET and consistently reported a good agreement for the assessment of myocardial viability between these 2 techniques. Additional studies have shown that FDG-SPECT can also predict improvement of LV function and heart failure symptoms after revascularization. Finally, recent developments, including coincidence imaging and attenuation correction, may further optimize cardiac FDG imaging (for the assessment of viability) without PET systems.Seminars in Nuclear Medicine 11/2000; 30(4):281-98. · 3.82 Impact Factor
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ABSTRACT: This study examines the quantitative accuracy, detection sensitivity, and time course of imaging the expression of a mutant herpes simplex type-1 virus thymidine kinase (HSV1-sr39tk) PET reporter gene in rat myocardium by using the PET reporter probe 9-(4-[18F]-Fluoro-3-Hydroxymethylbutyl)-Guanine ([18F]-FHBG) and a small-animal PET (microPET). In 40 rats, adenovirus expressing HSV1-sr39tk driven by a cytomegalovirus promoter (Ad-CMV-HSV1-sr39tk, 1x10(6) to 1x10(9) pfu) was injected through a thoracotomy directly into the left ventricular myocardium. After 3 days, myocardial perfusion was imaged with [13N]-ammonia for delineating the left ventricular myocardium, followed by imaging the expression of the reporter gene with intravenous [18F]-FHBG. The total myocardial [18F]-FHBG accumulation was quantified in percent of injected dose (%ID). Immunohistochemistry and autoradiography demonstrated HSV1-sr39tk enzyme (HSV1-sr39TK) and accumulation of [18F]-FHBG in the inoculated myocardium in 3 rats each. In 24 rats with various viral titers, the %ID was correlated with ex vivo well counting (r2=0.981, P<0.0001) and myocardial HSV1-sr39TK activity by tissue enzyme activity assay (r2=0.790, P<0.0001). Myocardial [18F]-FHBG accumulation was identified at viral titers down to 1x10(7) pfu. In 6 rats serially imaged up to day 17, myocardial [18F]-FHBG accumulation on microPET peaked on days 3 to 5 and was no longer identified on days 10 to 17. HSV1-sr39tk reporter gene expression can be monitored with [18F]-FHBG and microPET in rat myocardium quantitatively and serially with high detection sensitivity. Cardiac PET reporter gene imaging offers the potential of monitoring the expression of therapeutic genes in cardiac gene therapy.Circulation 01/2003; 107(2):326-32. · 15.20 Impact Factor
Molecular Cardiovascular Imaging
Lawrence W. Dobrucki, PhD and Albert J. Sinusas, MD*
*Section of Cardiovascular Medicine, Department of Internal Medicine,
Yale University School of Medicine, PO Box 208017, 3FMP , New Haven,
CT 06520-8017, USA.
Current Cardiology Reports 2005, 7:130–135
Current Science Inc. ISSN 1523-3782
Copyright © 2005 by Current Science Inc.
During recent decades, health care has become extremely
expensive and places a tremendous economic burden on our
society. The United States spends a greater percent of the
gross domestic product on health care than any other major
industrialized nation . The increasing health care burden
has resulted in a shift in emphasis from treating diseases to
the prevention of diseases. This reorientation brings new
challenges to the basic science community as well as need for
new clinical diagnostic tests and better risk stratification.
Targeted molecular imaging is expected to play a key role
in addressing these needs, providing a better understanding
of the pathophysiology, defining the progress of disease, and
evaluating the effects of new therapeutic intervention.
The Concept of Molecular Imaging
Molecular imaging is defined as the in vivo characterization
and measurement of biologic processes at the cellular,
molecular, and whole body level. The application of nuclear-
based approaches has been around for several decades and
has proved valuable for both basic investigation and clinical
practice. Molecular imaging with radiolabeled tracers allows
noninvasive, qualitative and repetitive in vivo imaging of
targeted macromolecules in various biologic systems and
animal models. Molecular imaging provides enormous
potential and applicability for evaluation of gene transfer,
tracking cell survival and apoptosis, and monitoring both
natural and pathologic biologic processes.
Molecular imaging requires two elements: 1) a molec-
ular probe that provides an analytical signal, and 2) a
method to monitor this probe. The most widely used
imaging strategies involve both direct and indirect
approaches. Direct molecular imaging requires the pres-
ence of a target epitope or peptide and is based on direct
probe-target interaction. Therefore, the magnitude of the
probe uptake and localization are directly related to the
targeted molecule. This approach has been extensively
used during the past two decades and involved use of both
native and engineered (more recently) radiolabeled mono-
clonal antibodies for imaging of cell-specific surface anti-
gens . Another common example of direct probe-
enzyme approach is positron emission tomography (PET)
or single-photon emission computed tomography
(SPECT) imaging of 18F-fluorodeoxyglucose (FDG) to
image glucose uptake [3,4]. In spite of the tremendous
value of direct imaging studies, these approaches cannot be
generalized to other targets of interest. With the advent of
targeted gene therapies, the direct approach would require
synthesizing a customized probe for the product of every
gene of interest. To overcome this limitation, indirect
molecular imaging strategies have been developed.
One of the indirect approaches utilizes reporter gene
technology [5••]. The concept of indirect gene reporter
imaging is more complex and involves multiple steps. The
first step involves introduction of a reporter gene into the
target tissue by various methods, including viral and non-
viral vectors. Then, the transcription of the reporter gene
and translation of the mRNA results in production of
reporter protein. The reporter gene product can be an
enzyme that converts a reporter probe to a metabolite that
is selectively trapped within transduced cells. This reporter
gene product-probe interaction may also be receptor-based
(ie, binding of radiolabeled ligand to cell surface recep-
tors). In addition to the clear flexibility of this approach,
the sensitivity may be greatly enhanced by the enzymatic
amplification of the probe signal, facilitating imaging both
the magnitude and location of reporter gene expression.
Imaging with radionuclides has historically played an
important role in detection of cardiovascular disease as well
as in risk stratification and prognostication. With the growth
of molecular biology have come new therapeutic
interventions and the requirement for new diagnostic
imaging approaches. Noninvasive targeted radiotracer-based
strategies require the development of new instrumentation
to meet these needs. This progress has been made possible
with the availability of many technologic advances, which
include dedicated micro single-photon emission computed
tomography (SPECT) and micro positron emission
tomography (PET) hybrid systems for small animal imaging.
This review is a brief overview on the subject of molecular
imaging. Basic concepts of molecular imaging are reviewed,
followed by description of current technologic advances, and
current applications to evaluate ischemic heart disease and
potential therapeutic intervention. The emphasis is on the
use of both SPECT and PET radiotracers, although other
imaging modalities are also briefly discussed.
Molecular Cardiovascular Imaging • Dobrucki and Sinusas131
Molecular Imaging Modalities
The advent of new molecular imaging strategies would be
impossible without a revolution in imaging technology that
has also occurred during recent years. A number of modali-
ties have been developed, although only a few are available
for a broad application in molecular imaging. Figure 1 illus-
trates the difference between the current imaging modalities.
Newer high-resolution CT, as well as ultrasound-based
approaches, represent medical imaging techniques that pro-
vide primarily anatomical images. Due to the popularity
and low cost of ultrasound instrumentation, efforts in recent
years have been devoted toward development of ultrasound
probes to be able to study biochemical processes at a molec-
ular level [6,7,8••]. However, these probes are still in an
early stage of development, tend to remain intravascular,
and may have limited sensitivity. MRI also offers very high
spatial resolution and unlimited depth penetration suggest-
ing this approach might be a more ideal approach for
molecular imaging. Unfortunately, MRI techniques suffer
from lack of widely available MRI-compatible molecular
probes and relatively low sensitivity. To overcome the lim-
ited sensitivity of MRI, novel strategies have been employed.
These include MRI signal amplification based on the cellular
internalization of highly paramagnetic probes such as iron
oxide or gadolinium nanoparticles. Indeed, there are a lim-
ited number of studies using paramagnetic nanoparticles to
track biologic processes, such as angiogenesis [9,10].
Optical imaging approaches utilize chemical processes
of bioluminescence and fluorescence to image biochemi-
cal processes both in vitro and in vivo. Due to the high sen-
sitivity, these techniques have been successfully applied to
track gene expression in vivo. In ATP-dependent biolumi-
nescence, various luciferase enzymes convert luciferin to
oxyluciferin, which emits visible photons that can be
detected and quantified with highly sensitive charge-
coupled device (CCD) cameras. In fluorescence imaging
approach, the analytical signal comes from visible photons
emitted from green (GFP) or red (RFP) fluorescent pro-
teins that are first excited with external energy source. In
spite of the favorable sensitivity and versatility of these
optical techniques, they suffer from very low spatial resolu-
tion and penetration depth due to visible light attenuation
by adjacent tissues. In addition, tomographic instruments
are not widely available.
Figure 1 compares the selected operational parameters of
each of these modalities with nuclear approaches. The
nuclear approaches (both PET and SPECT) offer favorable
sensitivity and acceptable resolution for in vivo tomographic
imaging. The quantity of the molecular probe which is
required to obtain detectable signal is also very low, in the
nanograms range. Indeed, for radiotracers, the number of
radioactive atoms per unit mass is very large (one curie of
freshly eluted pertechnetate, 99mTcO4-, corresponds to 10-7
moles). As a result, many receptor systems and intracellular
Figure 1. Comparison of the relative strengths
of different current imaging modalities.
Shading intensity represents the applicability
of a given technique in evaluation of
anatomy, physiology, metabolism, and
molecular processes. Darker shading
corresponds to high applicability. Table
illustrates selected operational parameters for
discussed modalities. BIO—bioluminescence;
CT—computed tomography; FLU—fluor-
escence; PET—positron emission tomogra-
phy; SPECT—single-photon emission
processes can be readily evaluated with minute concentra-
tions of radiotracers that will not cause a pharmacologic
effect . Nuclear imaging may be the modality of choice
for molecular imaging based on these issues and the numer-
ous basic and clinical studies using SPECT or PET modality.
Both SPECT and PET methodologies have advantages and
disadvantages based on the underlying physical and chemi-
cal differences of these approaches.
Single-photon emission CT imaging relies on detection
of photons emitted by chemical isotopes during radioactive
decay. The major disadvantage of SPECT imaging relates to
the attenuation of the low energy photons by body tissues. In
contrast to SPECT, PET imaging detects the high energy (511
keV) photons generated with positron decay. However, the
inherent resolution of PET is fundamentally limited to 1 to 3
mm by the physical behavior of positron decay. PET resolu-
tion is negatively affected by both the movement of the
positrons prior to annihilation, and deviation of the gener-
ated 511 keV photons from the exact 180° angular separa-
tion. Fortunately, PET imaging can overcome the attenuation
error by use of established approach for attenuation correc-
tion, and therefore tends to be more quantitative than
SPECT. On the other hand, SPECT has the potential for
simultaneous imaging of multiple, readily available SPECT
radiotracers. However, the generally short half-lives of PET
tracers allow for repetitive imaging of different radiotracers.
Moreover, the use of some PET radiotracers, such as 11C,
allows for the labeling of a molecule of interest without per-
turbing the biologic function.
The selection of which method is used, should be based
on a assessment of the properties of the biologic system
under evaluation, availability of a targeted and molecular
probe, as well as, accessibility to SPECT or PET instrumenta-
tion. Both PET and SPECT are tomographic that permits a
relatively precise localization of radiotracer retention; how-
ever, both modalities suffer from a lack of anatomic informa-
tion. Recently, nuclear imaging systems have been combined
with modality that provides high spatial resolution anatomic
information. The introduction of hybrid systems (PET-CT
and SPECT-CT) has greatly enhanced the performance and
accuracy of nuclear imaging. The CT component of these
hybrid systems is used to relate tracer signal with anatomical
landmarks and correct for nonuniform attenuation.
Another important technologic improvement has been
the development of both SPECT and PET instrumentation
dedicated for small animal molecular imaging. Until quite
recently, all commercially available scanners were designed
for human imaging and did not provide sufficient special
resolution for delineating tracer uptake in small animals.
Several groups have successfully constructed complete
microPET systems with approximately 2 mm spatial resolu-
tion [12,13]. The prototype microPET system designed at
the University of California-Los Angeles by Chatziioannou
et al.  has attracted the attention of basic scientists,
because this system provided a sufficient spatial resolution
for in vivo imaging of mice and rats. Since the initial proto-
type, many improved designs have been introduced, includ-
ing microPET R4 (1.85 mm resolution) , and more
recently microPET II scanner with remarkable 1.21 mm spa-
tial resolution [15,16]. The demand from many basic sci-
ence investigators for animal microPET has now led to
commercially available scanners . The major disadvan-
tage of dedicated microPET or hybrid microPET-CT systems
is their relatively high cost and potentially limited resolu-
tion (> 1.0 mm). Therefore much effort has been invested in
developing microSPECT systems, a lower cost alternative to
microPET. Initially, these efforts were hindered by a need for
pinhole collimators that sacrifice sensitivity for improved
spatial resolution. Early microSPECT prototypes were
unable to rotate heavy collimators around a small animal at
a precise constant radius of rotation without resulting in
severe misalignment imaging artifacts. Therefore, the proto-
type systems employed stationary detectors with rotation of
the animal in front of the detector. Recently, these difficul-
ties have been solved and novel hybrid microSPECT-CT
systems are now commercially available (X-SPECT, Gamma-
To resolve the issue of low sensitivity associated with
pinhole collimator-equipped microSPECT instruments,
recent efforts have been devoted toward construction and
evaluation of multipinhole collimators or coded aperture
plates. Coded aperture imaging is based on application of
multipinhole detectors in form of mathematically encoded
mask pattern [17,18]. This approach results in overlapping
of many projected pinhole images, which initially yield
noninterpretable image. However, by knowing the pinhole
pattern, computer postprocessing (decoding) yields a clear
image of the object. This technology remains in a develop-
ment phase. Preliminary results suggest that coded aperture
imaging permits high-resolution imaging with preserved
image count statistics and high signal to noise ratio. Despite
about one order of magnitude higher sensitivity than in con-
ventional collimator systems, coded aperture imaging works
best for images where activity is concentrated in small vol-
umes and interest is mainly in the bright components of the
image . Therefore, the coded aperture technique will
probably complement rather than replace traditional
nuclear imaging systems.
Another approach to increase the sensitivity of a SPECT
system without degrading the spatial resolution involves use
of multi-pinhole collimation. Multipinhole (7–14 pinholes
per collimator) tomography is an extension of conventional
single pinhole collimation. This technique differs from
coded aperture approach by arranging the pinholes in a way
that each pinhole may only view a portion of the object .
Therefore, all pinholes cover the whole field of view and
allow for a nonspherical field of view, which can be particu-
larly useful for whole-body imaging of small animals. An
alternative approach employs pinholes that partially overlap
resulting in more efficient detector coverage; however, this
Molecular Cardiovascular Imaging • Dobrucki and Sinusas133
overlapping leads to deterioration of the system matrix, thus
requiring novel reconstruction algorithms [20,21]. Several
multipinhole systems have been designed and evaluated dur-
ing recent years. The early systems, introduced in 1970s,
utilized seven pinholes, successfully provided three-dimen-
sional myocardial images . Since then, multipinhole sys-
tems were developed and used for breast cancer imaging as
well as small animal brain and myocardial imaging. All these
studies demonstrated the feasibility of the multipinhole
approach to increase the system sensitivity without degrad-
ing resolution. Therefore, this new imaging technique can
serve as a cost-efficient alternative or modification to existing
Applications of Cardiovascular
This article does not allow reviewing a vast scientific litera-
ture on studies using nuclear molecular imaging to moni-
tor cellular processes. These include imaging of receptors,
reporter probes and gene expression, metabolic processes,
myocardial inflammation, protein turnover, apoptosis,
angiogenesis, and imaging of unstable plaque. The follow-
ing section reviews several specific approaches to image the
process of postinfarction remodeling as well as to monitor
expression of the therapeutic gene in myocardial ischemia
model. We describe the typical indirect, receptor-based
approaches such as imaging of αvβ3 integrins and matrix
metalloproteinases (MMPs), as well as novel applications
of reporter gene imaging to study vascular endothelial
growth factor (VEGF) expression and cardiac gene transfer.
Imaging of Postinfarction Angiogenesis
With the development of novel therapies for the treatment
of ischemic heart disease directed at the stimulation of
angiogenesis, noninvasive targeted imaging strategies offer
far more than analysis of standard physiologic changes.
Additionally, molecular imaging targeted at the process of
postischemic myocardial remodeling will be critical for
defining the patients who will likely develop heart failure
as well as for defining the patients who will likely respond
to angiogenic therapy. The future for noninvasive imaging
of angiogenesis and remodeling process rests on the devel-
opment of targeted biologic markers.
Vascular endothelial growth factor (VEGF), a fundamen-
tal mediator of angiogenesis, is primarily activated in endo-
thelial cells, and therefore VEGF receptors represent potential
targets for imaging of mediators of ischemia-induced angio-
genesis. Indeed, recent studies using VEGF121 as a targeting
ligand labeled with indium-111 (111In), have proven the
applicability of this tracer in rabbit model of hindlimb
ischemia . Moreover, identification of VEGF receptors
could provide a tool for selecting the sites for local injection
of angiogenic factors or therapeutic gene vectors.
During recent years a significant breakthrough came
with discovery of the αvβ3 integrin that belong to a family
of αβ heterodimeric cell-surface receptors that mediate a
number of cellular processes associated with angiogenesis.
Numerous studies have been initiated to track angiogene-
sis using αvβ3 integrin as a target [23••]. These studies ini-
tially involved use of paramagnetically labeled anti-αvβ3
integrin antibody ; however, the difficulties associated
with slow tracer clearance and sensitivity were overcome by
the designing of radiolabeled constructs based on cyclic
Arg-Gly-Asp (RGD) peptides or peptidomimetics known to
bind to the αvβ3 integrin with high affinity. An 111In-
labeled quinolone (111In-RP748), which binds to the αvβ3
integrin, was used for both in vitro and in vivo imaging of
myocardial angiogenesis in canine and rodent models of
ischemia-mediated angiogenesis [25•]. Others have used
123I-labeled RGD peptide to assess myocardial angiogene-
sis in pigs with chronic ischemia  or 99mTc-labeled
RGD peptide (NC100692) in rodent model of hindlimb
ischemia-induced angiogenesis . All of these early
studies suggest that the radiolabeled αvβ3 targeted agents
may be valuable in noninvasive imaging of both natural as
well as therapeutic angiogenesis.
Left ventricular (LV) remodeling, defined as the adverse
changes in LV structure and geometry that occur following
myocardial infarction (MI), can give rise to LV dysfunction
and progressive heart failure. There is a striking relationship
between the rate of LV remodeling and both morbidity and
mortality in post-MI patients. MMPs also contribute to the LV
remodeling; thus, MMPs represent a potential target for
molecular imaging of the remodeling process. Indeed, recent
effort has been placed in developing nonpeptide markers for
MMP activity that resemble the structural configuration of
pharmacologic MMP inhibitors, but do not possess native
MMP inhibitory activity. Recently, Su et al.  have success-
fully evaluated a MMP targeted SPECT tracer (111In-RP782)
that bind to the catalytic domain of MMP to monitor tempo-
ral changes in MMP activation in murine model of MI.
Similar studies with a 99mTc-labeled nonspecific MMP inhibi-
tor (RP805) have been performed using a dedicated
microSPECT-CT hybrid system in rats (Fig. 2).
Reporter Gene Imaging
Gene transfer, defined as the transfer or expression of DNA to
somatic cells with a resulting therapeutic effect, is currently
the most promising therapeutic approach of molecular med-
icine. However, to assess the efficiency of vector delivery, gene
expression and therapeutic effect, novel imaging methods
need to be developed. To address this demand, two reporter
gene imaging approaches are being intensively developed
and are currently used in animal models.
The first approach uses an enzyme-based reporter gene,
whereas the second approach employs a receptor-based
reporter gene [5••]. In the enzyme-based technique, herpes
simplex virus type 1 thymidine kinase (HSV1-tk) uses 131I- or
18F-labeled thymidine analog probes as the substrate, which
is further phosphorylated and trapped within the cells.
Radioactive gene product can be then detected and quanti-
fied using SPECT or PET modality, respectively. The second
approach utilizes different receptor systems like dopamine 2
receptor (D2R), somatostatin type 2 receptor (SSTr2) or
human sodium/iodide symporter (hNIS) gene, where a radi-
olabeled receptor probe is trapped on or within the cells
expressing a particular receptor system.
Recently, Inubushi et al.  and Wu et al.  demon-
strated the feasibility of imaging the location, magnitude
and duration of a single PET reporter gene (HSV1-tk
mutant derivative, HSV1-sr39tk) expressed in the rat myo-
cardium and expression of two PET reporter genes (HSV1-
sr39tk and mutant D2R) linked together by an internal
ribosomal entry site [31•]. Furthermore, the same group of
investigators proposed substitution of one of the PET
reporter genes with a therapeutic gene, in order to monitor
expression of the therapeutic gene by imaging the linked
reporter gene. The feasibility of this approach has been suc-
cessfully demonstrated in recent series of experiments by
using VEGF121 as the therapeutic gene linked with a gene
to be imaged (HSV1-sr39tk) in rodent model of MI [5••].
This concept can be used to evaluate other therapeutic
genes in basic research as well as in future clinical trials.
The presented examples of molecular imaging in nuclear car-
diology provide an insight into the future of noninvasive
imaging. The future rests on both the development of tar-
geted biologic markers of the physiologic processes (ie, VEGF
receptors, integrins), reporter gene techniques to evaluate
cardiac gene therapy as well as novel instrumentation.
Dedicated microSPECT-CT and microPET-CT hybrid
imaging systems for small animal imaging are currently
commercially available and should result in a tremendous
growth in the field of molecular imaging. Despite high
initial costs of instrumentation and training of personnel for
small animal imaging, this initial preclinical step promises
to advance our understanding of fundamental biologic
functions in living systems.
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