Diagnostic

Diagnostic use
use of
of radiopharmaceuticals
radiopharmaceuticals in
in
nuclear
nuclear medicine
medicine (( Heart
Heart ))
 Anatomy and Physiology
The cardiovascular system consists of the heart and blood vessels
(arteries and veins) and governs the circulation of blood in the body.
The heart works as a pump and circulates the blood through blood
vessels to the different parts of the body.
The heart is divided into four chambers: the right atrium, left atrium,
right ventricle, and left ventricle (Fig. 13.27). Deoxygenated blood from
the systemic circulation is received by the right atrium from the
superior and inferior vena cavae and then passes into the right ventricle
via the tricuspid valve.
Blood is then pumped from the right ventricle via the pulmonary artery
into the lungs, where it is oxygenated by diffusion of oxygen from the
alveoli, and carbon dioxide from the blood is released. Oxygenated
blood passes through the pulmonary veins into the left atrium and then
to the left ventricle via the mitral valve. The left ventricle pumps the
blood into the aorta, which distributes it to the systemic circulation.
 The heart goes through a cycle of diastole and systole that maintains
appropriate blood pressures in its four chambers as well as in the blood
vessels. Diastole is the period of dilatation or expansion of the heart,
and systole is the period of contraction of the heart during which blood
is forced into the aorta and pulmonary artery.
The passage of blood from the right atrium up to the aorta is governed
by the above cardiac cycle and by a number of valves present between
different atrial and ventricular chambers.
The valves are so constructed that only one-way passage of blood is
allowed and regurgitation is prevented. The cardiac cycle is a well
coordinated function of the heart and any deviation from it leads to a
variety of cardiac abnormalities.
The cardiac output is the amount of blood pumped by the heart per
unit time. It is 46 liters/min for a man at rest. The cardiac output
depends on the amount of blood the ventricles expel during systole,
the heart rate, and the degree of venous lling.
 The heart muscle receives its blood supply
from the coronary arteries, which arise from
the rst part of the aorta. The coronary
arteries penetrate the mass of cardiac muscle
and end in capillaries.
The latter connect to venules and nally to the
coronary veins. About 5% of the cardiac
output 200300 ml/min) passes through the
coronary circulation. However, during severe
exercise the coronary blood ow may increase
to 11.5 liters/min.
 FIGURE 13.26. Typical whole body bone scan obtained with 99mTc
MDP 2 h after injection indicating metastatic lesions at various
sites in the body.
 The left coronary artery consists of left anterior descending (LAD) and left
circumex (LCx) arteries, whereas the right coronary artery (RCA) branches
into a posterior descending artery (PDA) and a posterior left ventricular
branch. Coronary artery diseases (CAD) are caused by lack of optimal arterial
blood supply to the heart. Atherosclerosis is a complex process of cholesterol
deposition, inammation and plaque formation resulting in narrowing of the
arteries thus causing CAD. Complete blockage of artery causes myocardial cell
death, which is termed as myocardial infarction (necrosis), whereas partial
blockage leads to ischemia (reduced blood perfusion) of the tissues. Ischemic
heart disease along with hypertension compromises the cardiac output and
contractile function and can lead to congestive heart failure (cardiomyopathy).
In such cases, the ejection fraction and wall motion of the heart will be
reduced. The hibernating myocardium is a dysfunctional myocardium with
ischemia, but with preserved cell viability. Myocardial perfusion imaging using
SPECT and PET radiopharmaceuticals successfully identies the infracted
versus ischemic myocardium.
 The heart requires constant supply of energy to sustain
its pumping function, which is derived from the
hydrolysis of ATP that results from the aerobic
metabolism.
The presence of myocardial metabolism indicated the
cell viability. Both nonesteried free fatty acid and
glucose are the two essential metabolic substrates to
provide energy to the heart.
In normal myocardium in the fasting estate, free fatty
acid is the preferred substrate supplying up to 80% of
the required cardiac energy, whereas in the fed state,
plasma glucose and insulin level increase and glucose
becomes the predominant substrate for energy source.
Based on this concept,18 F-FDG has been used as a
metabolic agent to determine the myocardial viability.
Radiopharmaceuticals and imaging
technique
Various radiopharmaceuticals for
myocardial imaging are listed in Table
13.6.
Perfusion Imaging
Characteristics of different SPECT
myocardial perfusion
radiopharmaceuticals are given in Table
13.7.
 Tl-Thallous Chloride
201

201Tl-thallous chloride is used for myocardial perfusion

imaging. After intravenousadministration, nearly 85%of
the administered dosage is extracted by the myocytes
during the rst pass of the tracer. Blood clearance is
rapid, with only 5% remaining in the blood 5 min after
injection. It is mostly excreted by the kidneys and the
whole-body biological half-life is about 10 days. Maximum
myocardial uptake (~4%) of 201Tl occurs about 510 min
after injection (Atkins et al. 1977). Its myocardial washout
has a t1/2 of about 4 h. The myocardial uptake of 201Tl is
linearly proportional to the blood ow, arterial
concentration of the tracer, and myocardial mass, but can
be reduced at high ow rates.
 Although thallium belongs to group IIIA, thallous
ion behaves like K+, because they are both
monovalent and have similar ionic radii. The
extraction of thallium ions by myocytes requires
that cations traverse the capillary wall, interstitial
space, and myocyte membrane. The barrier at the
capillary wall is blood-ow dependent, and Tl+ is
transported through the cell membrane by active
transport by the Na+ - K+ -adenosine
triphosphatase (ATPase) enzyme, which is
facilitated by depolarization and repolarization of
the cell membrane.
 Imaging is performed under resting and stress (e.g., exercise)
conditions by means of a gamma camera. Normally, the patient is asked
to exercise on a treadmill or a bicycle and 23 mCi (74111 MBq) 201Tl is
injected at the peak of the exercise period. Imaging of the heart is begun
510 min after injection and completed in about 30 min. After about 34
h of resting, the patients heart is again imaged under identical
conditions. The latter images are called the redistribution images.
Images can be obtained either by SPECT alone or the SPECT/CT method.
CT images are obtained for coregistration with as well as for attenuation
correction of SPECT images. In the SPECT mode, data are collected by a
multi-head camera in a 128 128 matrix at small angle intervals (36)
over 180 or 360 around the heart. CT data are then used for attenuation
correction of SPECT data. Reconstructed images of both SPECT and CT
are obtained by using appropriate algorithm in transverse, sagittal and
coronal projections. Coregistration of SPECT and CT images is
accomplished manually or by software. However, there is a marked
mismatch in the fusion of the two sets of images, because of respiratory
and cardiac motion. This is why there is a great deal of limitation in
myocardial perfusion SPECT/CT studies.
 Gated SPECT can be performed by collecting the data in 15-ms to 75-ms segments
during each cardiac cycle (i.e., between two consecutive R-waves). Normally for SPECT,
data are acquired in 816 frames per cardiac cycle and over many cardiac cycles. Since
201Tl uptake is blood-ow dependent, during the exercise test the normal tissues
accumulate more thallium(due to high blood ow) than ischemic tissues (reduced blood
ow), thus the latter resulting in a defect on the stress image. In the resting period
(redistribution), tissues with high 201Tl uptake (normal) have a faster washout than
those with low uptake (ischemic but viable), and tissues that have received less
thallium relative to the blood concentration will continue to accumulate 201Tl.
Furthermore, a large portion of washout thallium comes from tissues other than the
cardiac tissues and is presented to myocardium for extraction. Thus, thallium ions
undergo continuous exchange between extracellular and intracellular compartments,
leading to what is called the redistribution of thallium. At a certain time later, there is
an equilibrium between the intracellular and interstitial compartments of activity and
the defect seen in the mildly perfused areas on the stress image will disappear on the
34 h redistribution images. However, the initial uptake of thallium in infarcted tissues
is so low that at equilibrium, the defect does not disappear on the redistribution image.
Thus, a defect on both stress and redistribution images indicates an infarct, whereas a
defect on stress images that lls in on redistribution images suggests ischemia.
Ischemic defects are mostly reversible and viable, and the patient is likely to benet
from revascularization procedures such as bypass surgery or angioplasty. Myocardial
SPECT images (both normal and abnormal) obtained with 201Tl are shown in Fig.
13.28.
 In patients who cannot perform treadmill
exercise, myocardial stress is
induced by intravenous administration of a
vasodilator such as dipyridamole
(Persantine), lexiscan or adenosine. The latter
causes more side effects (e.g.,
chest pain, ushing, headache, etc.) than the
former, but they are more
transient. Some of these side effects can be
reduced by intravenous administration
of aminophylline.
FIGURE 13.28. 201Tl SPECT images (transverse) of the heart during
the stress (S) and redistribution (R) studies separated by 4 h. (a)
Normal. (b) Ischemia (arrow). (c) Infarct (arrow).
 It has been demonstrated that some persistent defects that are seen on the
early redistribution images (34 h after injection) are lled in with 201Tl on
the delayed distribution images at 824 h (Kiat et al. 1988). Time to
complete redistribution depends on the severity of stenosis and the blood
concentration of 201Tl. To elevate blood concentration of 201Tl, it is
suggested that a second injection of 1 mCi (37 MBq) 201Tl would facilitate
the myocardial uptake in ischemic but viable regions that would otherwise
be considered as persistent defects (Dilsizian et al. 1990). Three methods
are employed:
(1) reinjection after the redistribution study and imaging 1520 min later,
(2) reinjection immediately before the redistribution study and imaging
1520 min later,
(3) reinjection immediately after stress imaging and imaging 34 h later.
Methods 1 and 2 tend to show increased gut activity, which makes the
interpretation of the images somewhat difcult. Method 3 offers the
advantage of optimal clearance of the gut activity because of the longer
time allowed between the reinjection and redistribution imaging. Using this
reinjection technique, almost 4045% of the 34 h redistribution defects
were identied to be viable, which otherwise would have been considered as
persistent defects, and thus these patients beneted from revascularization
by coronary artery bypass graft (CABG) and angioplasty.
 The radiation characteristics of Tl are poor. The
low-energy photons (6980 keV) of 201Tl degrade
the spatial resolution of the images due to
scattering. The long half-life of 73 h increases the
radiation dose to the patient. It is cyclotron-
produced and therefore quite expensive. As
substitutes for 201Tl, two99mTc-labeled
radiopharmaceuticals (99mTc-sestamibi and 99m
Tc-tetrofosmin) are used for SPECT myocardial
perfusion imaging. 82Rb-rubidium chloride and
13N-ammonia are used for PET myocardial
perfusion imaging.