Diagnostic agents

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.

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)

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.

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: Preliminary 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.

Water soluble organic iodinated radiopaque 1.Diatrizoate sodium

I CH3COHN I COONa I NHCOCH3

sodium-3,5-bis(acetylamino)-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

2. Ipodate Sodium (OragrafinR)

CH2CH2COONa I I N I N CH3

CH3

Sodium-3-[[(dimethylamino)methylene]amino]-2,4,6riiodohydrocinnamate. Orally as capsule Cholecystography (gallbladder) Maximum concentration in the hepatic and biliary ducts occurs in 13 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.

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 I 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.

C 2 H5 COOH I NH2 I

2. Iocetamic acid (CholebrineR)

O H3 C I N

CH3 CH COOH I NH2 I

N-Acetyl-N-(3-amino-2,4,6-triiodophenyl)-b-aminoisobutyric acid Administered orally 10-15 h., before x-ray film of the gall bladder.

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.
H2 N CONHCH2COONa

O2 N

COCl + H2NCH2COOH

- HCl

O2 N

CONHCH2COOH

1- red. H2 N 2- equiv. NaOH

CONHCH2COONa

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

O NaSO3 N H O H N SO3Na

Indigotindisulfonate sod. 5,5`-Indigotindisulfonate disodium For determination of renal function and to locate the uretheral orifices, it appear in urine after 10 min.

B- Agent for liver function test

1.Sulfobromophthalein (BromosulphaleinR)
OH NaO3S OH Br Br O Br Br O SO3Na

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.

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.
Cl Cl O Cl Cl O + 2 O HO OH reaction condensation tetrachlorofluorescein Iodination Rose Bengal

+ NaO I

I O

I O

I Cl Cl Cl COONa Cl

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).

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.

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-(2,6dimethylphenylcarbamoylmethyl)-iminodiacetic acid (HIDA).

R O O TC O O N R
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.

N O O

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

H N
123

CH3 CH3

IMP N-Isopropyl-[I123]-piodoamphetamine

CH3

OH H3C N CH3 I123 N CH3

CH3

HIPDM N,N,N`-Trimethyl-N1-[2-hydroxy-3-methyl-5-iodobenzyl]-1,3propane-diamine