Radio Pharmaceuticals

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RadiopharmaceuticalsDesign and safety handling Nahla S. Barakat, Ph.DDept. of Pharmaceutics College of Pharmacy King Saud University 1429/2008

Description

Radiopharmaceuticals used in cancer treatment are small, simple substances, containing a radioactive isotope or form of an element. They are targeted to specific areas of the body where cancer is present. Radiation emitted from the isotope kills cancer cells. These isotopes have short half-lives, meaning that most of the radiation is gone within a few days or weeks.

Application of radiopharmaceuticals Treatment of disease: (therapeutic radiopharmaceuticals) Chromic phosphate P32 for lung, ovarian, uterine, and prostate cancers Sodium iodide I 131 for thyroid cancer Samarium Sm 153 for cancerous bone tissue Sodium phosphate P 32 for cancerous bone tissue and other types of cancers Stronium chloride Sr 89 for cancerous bone tissue

Chromic phosphate P 32 is a suspension that is delivered through a catheter, or tube, inserted into the sac surrounding the lungs, or into the abdominal or pelvic cavities. The usual dosage is 15-20 millicuries for abdominal administration and 10 millicuries for administration to the lung sac. Chromic phosphate P 32 also may be injected into the ovaries or prostate. Sodium Iodide I 131 is taken by mouth as a capsule or a solution. The usual dose for treating thyroid cancer is 30-200 millicuries, depending on age and body size. Doses may be repeated. Treatment usually requires two to three days of hospitalization. For this therapy to be effective there must be high levels of thyroid-stimulating hormone (TSH, or thyrotropin) in the blood. This hormone can be injected prior to treatment.

Strontium-89 is injected into a vein. The usual dosage is 4

millicuries, depending on age, body size, and blood cell counts.Repeated doses may be required. The usual dosage of samarium Sm 153 lexidronam is 1 millicurie per kg (0.45 millicurie per lb) of body weight, injected slowly into a vein. Repeated doses may be necessary. Because samarium Sm 153 lexidronam may accumulate in the bladder, it is important to drink plenty of liquid prior to treatment and to urinate often after treatment. This reduces the irradiation of the bladder.

The dosage of sodium phosphate P 32 depends on age, body size,blood cell counts, and the type of treatment. The usual dosages range from 15 millicuries. Repeated doses may be required. Radiopharmaceuticals usually are not recommended for use during pregnancy. It is recommended that women do not become pregnant for a year after treatment with sodium iodide I 131. Breast-feeding is not possible during treatment with

radiopharmaceuticals.

Precautions Before Treatment With Sodium Iodide I 131Foods containing iodine, such as iodized salt, seafoods, cabbage, kale, or turnips, should be avoided for several weeks prior to treatment with sodium iodide I 131. The iodine in these foods will be taken up by the thyroid, thereby reducing the amount of radioiodide that can be taken up. Radiopaque agents containing iodine sometimes are used to improve imaging on an x ray. A recent x-ray exam that included such an agent may

interfere with the ability of the thyroid to take up radioiodide.

Precautions After Treatment With Radiopharmaceuticals Strontium-89, samarium Sm 153 lexidronam, and large total doses of sodium iodide I 131 may temporarily lower the

number of white blood cells, which are necessary for fightinginfections. The number of blood platelets (important for blood clotting) also may be lowered. Precautions for reducing the

risk of infection and bleeding include:avoiding people with infections seeking medical help at the first sign of infection or unusual

bleeding using care when cleaning teethavoiding touching the eyes or inside of the nose avoiding cuts and injuries

It is important to drink plenty of liquids and to urinate often after treatment with sodium iodide I 131. This flushes the radioiodide from the body. To reduce the risk of contaminating the environment or other people, the following procedures should be followed for 4896 hours after treatment is sodium iodide I 131: avoiding the handling of another person's eating utensils, etc.

avoiding close contact with others, especially pregnant womenwashing hands after using or cleaning the toilet using separate washcloths and towels washing clothes, bed linens, and dishes separately flushing the toilet twice after each use

I131 THERAPY PROCEDURES Minor therapies of I131 are single doses of 30 mCi or less. Major therapies of I131 are single doses greater than 30 mCi.

Handling Instructions

All I 131 should be opened under a fume hood prior to administration to a patient to allow for escape of vapor in the vial. The activity of each dosage shall be measured in a dose calibrator and verified to be within 10% of the prescribed dose. Since the exposure rate on the outside of the lead pig and shipping box may be quite high, adequate precautions must be taken when transporting sources.

Major Therapies Patients receiving major therapeutic doses of I131 must be admitted to the hospital. The patient must have a private room and bath. The room must also be approved by the Radiation Safety Office, taking into consideration areas adjacent to, above, and below where radiation levels must be within certain limits. Before the dose is administered, the room must be prepared by

Radiation Safety.This involves covering the floor with plastic or absorbent paper and covering various articles the patient may touch such as

the telephone, TV control, etc.

The dose is usually administered with the patient sitting on theedge of the bed. The bedside table should be covered with an absorbent pad. A physicist or technician from Radiation Safety must be present during administration and is responsible for disposing of the waste. The patient must remain hospitalized until the activity is less than

30 mCi or the measured dose rate at one meter from thepatient is less than five millirems per hour. The nursing instruction form contains specific rules for care of

the patient by nurses, visitors restrictions, and handling waste,linens, and eating utensils.

Patient rooms used for major therapies may not be released for use by other patients until documented surveys by Radiation Safety staff demonstrate that there is no removable contamination in excess of 200 dpm/100 cm2.

Therapeutic procedures can usually be divided into two classes: Treatment with sealed sources, which are mechanically inserted. Treatment with solutions.

Sealed sources are encapsulated and therefore the risk of contamination is very small Ex. Radiopharmaceutical Iodine-125 seeds, used to treat prostate cancer. Ex of radiopharmaceutical solutions, Iodine-131, Strontium-89

As an aid in the diagnosis of disease (diagnosticradiopharmaceuticals) Radiopharmaceuticals used in tracer techniques for measuring physiological parameters (e.g. 51 Cr-EDTA for measuring glomerular filtration rate). Radiopharmaceuticals for diagnostic imaging (e.g.99m

TC-methylene diphosphonate (MDP) used in bone

scanning).

Radiopharmaceuticals can be classified into four categories: 1- Ready-for-use radioactive products.

2- Radionuclide generators.3-Non-radioactive components (kits) for the preparation

of compounds with a radioactive component (usuallythe elute from a radionuclide generator). 4- Precursors used for radiolabeling other substances before administration.

Radiopharmaceutical products include inorganic compounds, organic compounds, peptides, proteins, monoclonal antibodies and fragments and oligonucleotides labeled with radionuclide

with half-lives varying from a few minutes to several days.

There are three units related to radiation: ( R) the roentgen for exposure Is the amount of x or radiation that produces ionization of one electrostatic unit of either positive or negative charge per cubic centimeter of air at 0 C and 760 mmHg.

(rad) radiation absorbed dose is a more universal unit, it is ameasure of the energy deposited in unit mass of any material by any type of radiation.

The dose equivalent unit (rem) roentgen equivalent manrem has been developed to account for the differences in effectiveness of different radiations in causing biological damage. In radiobiology, the rem is defiend as Rem= rad RBE

RBE is the relative biological effectiveness of the radiation.

The basic unit for quantifying radioactivity (i.e. describes the rate at which the nuclei decay).

Curie (Ci):A unit of radioactivity. A curie is defined as 3.7 x 1010 disintegrations per second. In 1980, The new basic unit for quantifying radioactivity. Becquerel (Bq):

A unit of radioactivity. One becquerel is equal to 1 disintegrationper second.

Generator, Radionuclide:

A device in which a short-lived daughter is separatedchemically and periodically from a long-lived parent adsorbed on adsorbent material. For example,99Mo 99mTc

is separated from

from the molybdenum generator by eluting with saline.

Half-Life (Tl/2):A unique characteristic of a radionuclide, defined by the time during which an initial activity of a radionuclide is reduced to one half. It is related to the decay constant () by tl/2 = 0.693/.

Hot CellA lead shielded total containment cabinets providing an environment of different classes. Ionization Chamber: A gas-fi1led instrument used to measure radioactivity or exposure in terms of ion pairs produced in gas by radiations. Isotopes: Nuclides having the same atomic number, that is, the same number of protons in the nucleus, but different number of neutrons. Examples are 14C 6 and 12C6 .