Diagnostic agents

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Diagnostic agents
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Diagnostic agents are compounds used in diagnosis
to detect impaired function of the body organ and
to recognize abnormalities in tissue structure,
these agents applied directly to the body.
Classification of Diagnostic Agents I- a- Radio
opaque for radiography. b- Radiopharmaceutical
for scintigraphy. II- Compounds for testing
functional capacity. III- Compounds modifying a
physiologic action.
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Factors that often determine the usefulness of
diagnostic agents are The ideal contrast agent
(radiopaque) should have 1.Ready availability
and low cost 2.Excellent x ray absorption 3.
chemical composition (stability) 4.Solubility(high
water solubility, low viscosity) 5.The ability
to be administered for selective tissue uptake
and excretion 6.Minimal toxicity (minimal osmotic
effect)
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I- Radioopaque for radiography Roentgen's X rays
and computed tomography. In conventional roentgen
examination tissues are visualized according to
their ability to attenuate a beam of X-rays
before strike a detector. The attenuation varies
according to the relative density of the tissue.
Bone absorbs large percentage of the rays appears
white on the exposed film. The air filled lung
is translucent relative to bone and appears
darker on the exposed film. Depending on the
relative opacity of radiopaques to X-rays.
Substances that increase the density of a tissue,
thereby rendering it opaque to x-rays are called
positive contrast agents.
Radiopaque DA include organic and inorganic
compounds which have the property of casting a
shadow on X-ray film. Barium sulphate is the most
inorganic compounds that often used as suspension
in roentgraphic (X-ray) examination of
gastrointestinal tract.
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Organic iodinated radiopaque
I2 in strong covalent linkage. I2 was observed
to contribute opacity to x-ray. They are more
opaque and used by two mean 1)
Systemic Administered orally or IV to examine
kidney (urography) or liver (cholecystography)
for visualization of renal cavities, ureter,
biliary tract, blood vessels. Precaution Prelimin
ary test for sensitivity. Cathartic given the
night before the injection. Food, liquids
withhold for at least 18h., to prevent blurring
of the picture.
2) Retrograde method Introduction of diagnostic
agent by mechanical means into bladder, ulcer
area or urethra by cystoscop through Catheter.
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Water soluble organic iodinated radiopaque
1.Diatrizoate sodium sodium-3,5-bis(acety
lamino)-2,4,6-triodobenzoic acid, as solution
orally and injection used in urographic studies
(urinary tract examination). Diatrizoate
meglumine (methylglucamine) CH2NHCH3 Meglumine
salt is better tolerated than the corresponding
sodium salt
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2. Ipodate Sodium (OragrafinR)
Sodium-3-(dimethylamino)methyleneamino-2,4,6-r
iiodohydrocinnamate. Orally as capsule
Cholecystography (gallbladder) Maximum
concentration in the hepatic and biliary ducts
occurs in 1-3 h., and persists for about 45 min.
Cholecystopexy is any gallbladder disease and to
aid in diagnosing the disease a compound is
desirable that is opaque to x-ray and well
concentrated in the gallbladder and the bile duct.
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3.Metrizamide Angiographic agent for
visualization of blood vessels ,non ionic water
soluble contrasting agent The drug of choice for
most cardiac angiographic procedure
Water insol. organic iodinated radiopaque
Iopanoic acid (TelepaqueR)
3-Amino-a-ethyl-2,4,6-triiodohydrocinnamic acid
Orally Diagnosing gallbladder and bile duct. It
bound to serum albumin and converted to water
soluble glucuronoide conjugate and excreted in
the bile ,thus concentrated in the gall bladder.
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2. Iocetamic acid (CholebrineR)
N-Acetyl-N-(3-amino-2,4,6-triiodophenyl)-b-aminois
obutyric acid Administered orally 10-15 h.,
before x-ray film of the gall bladder.
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II- Compounds for Testing Functional Capacity
A- Agents for kidney function test Aminohippurate
sodium IV injection, sensitive to light, we add
sod. bisulfite to prevent darkening of the
solution.
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The sodium salt is excreted by tubular epithelium
of the kidney and by glomerulus thus determining
the functional capacity of tubular excretary
mechanism.
2. Indigo Carmine, IV injection
Indigotindisulfonate sod. 5,5-Indigotindisulfonat
e disodium For determination of renal function
and to locate the uretheral orifices, it appear
in urine after 10 min.
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B- Agent for liver function test
1.Sulfobromophthalein (BromosulphaleinR)
4,5,6,7-Tetrabromo-3,3-disulfophenolphtholein
disodium The compound taken parentally and
removed through liver, the amount remained in
blood measured colourimetry after certain time
interval. The rate at which the dye removed from
blood is a measure of hepatic function.
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2.Rose Bengal
Tetraiodotetrachlorofluorescein
Used as a test for liver function injected in
saline intravenously and the liver almost remove
the dye from blood stream a normally functioning
liver will remove 50 of the dye within 2
min. The dye and patient receiving it should be
protected from light.
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Radiopharmaceutical
Neutron and protons (mass of atom) exist in
well-defined energy levels in the nucleus held
together by strong forces. They have a particular
ratio, an excess of either proton or neutron
results in an unstable nucleus state and an
energy state other than the stable state which
will spontaneously transform itself into stable
one. This phenomenon of spontaneous nuclear
transformation to attain stability is always
accompanied by a release of energy and is called
(radioactivity). Atoms with the same number of
proton and different number of neutron are called
(isotopes).
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The energy released from radioactive is usually
detected by its ability to ionize the atom of
matter through which it passes. The Rad is a
quantitative measure of radiation energy
absorption The nuclides used in
radiopharmaceutical (radioisotope tracer) must
have suitable short half-life and high yield of
g-rays (50-500 KeV) without causing excessive
tissue irradiation from other emission (e.g. from
high energy b particles).
Many radio nuclides may be used as scanning
agents for organ or tumors visualization.
Scanning with radio nuclides not only gives an
indication of the size, shape and position of an
organ and aids in the detection of tumors, cysts
or abscesses but also allow assessment of the
blood supply and the specific function of the
organ. The official pharmacopoeia recognize the
following radiopharmaceuticals in various dosage
forms and diagnostic aids Co57, Co58 in
pernicious anemia I131, Cr51. Blood volume
determination P32, Au198 in chemotherapy as
antineoplastic.
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Radionuclide and radiopharmaceuticals for organ
imaging The ideal radionuclide should be readily
incorporated into carrier molecules. The
principal instrument for displaying images is the
gamma camera. These images may be planer or
tomographic. I131 is the most frequently used
radionuclide of I2 in organ imaging
radiopharmaceuticals it is readily incorporated
into a variety of organic molecules.
Technetium 99m It used to visualize thyroid and
brain stable in water as either pertechnetate
anions TcO4- or insoluble technetium oxide
(TcO2). The following chelate of Tc in which the
organic moiety retains the physiologic capacity
to enter the enterohepatic cycle while it remains
bound together with the technetium. Tc-99m
labeled dimer of N-(2,6-dimethylphenylcarbamoylmet
hyl)-iminodiacetic acid (HIDA).
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To be usual as an organ imaging agent,
radiopharmaceutical must be able to localize
selectively in a particular organ or tumor.
Usually, a 10 fold difference in uptake of
radioactivity by the target agent versus
surrounding nontarget areas is sufficient for
imaging purposes.
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Brain imaging Most intracranial lesions alter
the blood brain barrier so that various
radiopharmaceuticals can penetrate inaccessible
regions and localize in and around the
lesion. The most commonly used agent for brain
imaging is Tc-99m. Other radiopharmaceuticals
have become available that are sufficiently
lipophilic to available the blood brain
barrier. e.g. IMP and HIPDM
IMP N-Isopropyl-I123-p-iodoamphetamine
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HIPDM N,N,N-Trimethyl-N1-2-hydroxy-3-methyl-5-io
dobenzyl-1,3-propane-diamine