Radio Pharmaceuticals

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Radiopharmaceuticals Design and safety handling Nahla S. Barakat, Ph.D Dept. of Pharmaceutics College of Pharmacy King Saud University 1429/2008

Transcript of Radio Pharmaceuticals

Page 1: Radio Pharmaceuticals

RadiopharmaceuticalsDesign and safety handling

Nahla S. Barakat, Ph.DDept. of Pharmaceutics

College of PharmacyKing Saud University

1429/2008

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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.

Description

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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

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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.

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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.

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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 1–5 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.

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Precautions Before Treatment With Sodium Iodide I 131

Foods 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.

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Precautions After Treatment With RadiopharmaceuticalsPrecautions 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 fighting

infections. 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 teeth

avoiding touching the eyes or inside of the nose

avoiding cuts and injuries

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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 48–96 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 women

washing 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

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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.

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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.

    

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The dose is usually administered with the patient sitting on the

edge 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 the

patient 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.

    

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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.

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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

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As an aid in the diagnosis of disease (diagnostic

radiopharmaceuticals)

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).

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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 (usually

the elute from a radionuclide generator).

4- Precursors used for radiolabeling other substances

before administration.

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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.

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There are three units related to radiation:

( R) the roentgen for exposure

Is the amount of x or γ radiation that produces ionization of one electrostatic unit of either positive or negative charge per cubic centimeter of air at 0 ºC and 760 mmHg.

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(rad) radiation absorbed dose is a more universal unit, it is a

measure of the energy deposited in unit mass of any material

by any type of radiation.

The dose equivalent unit (rem) roentgen equivalent man

rem 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.

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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 disintegration

per second.

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Generator, Radionuclide:

A device in which a short-lived daughter is separated

chemically and periodically from a long-lived parent adsorbed

on adsorbent material. For example, 99mTc is separated from

99Mo

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 (λ) by tl/2 = 0.693/λ.

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Hot Cell

A 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.

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Labeled Compound:

A compound containing radionuclide as integral component of the molecule.

Radiolysis:

A process by which radio labeled compounds are broken up by radiations from the radionuclide in labeled molecules.

Radiosynthesizer Unit (RSU)

A closed-system device for the automated synthesis of radioactive drug substances. The system may be controlled by graphical computer software programs.

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Radionuclide Purity:

The fraction of the total radioactivity in the form of the stated

radionuclide. Any extraneous radioactivity such as 99Mo in 99mTc-radiopharmaceuticals is an impurity.

Radiopharmaceutical:

A radioactive drug that can be administered safely to humans

for diagnostic and therapeutic purposes.

Sievert (Sv):

The unit of absorbed dose equivalent and equal to 100 rem.

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Standard operating procedure (SOP):

An authorized written procedure giving instructions for

performing operations not necessarily specific to a given

product or material (e.g. equipment operation, maintenance

and cleaning; validation; cleaning of premises and

environmental control; sampling and inspection). Certain

SOPs may be used to supplement product-specific master and

batch production documentation.

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Target Material

A chemical substance which is bombarded with nuclear

particles to produce a desired radionuclide .

Tracer

A radionuclide or a compound labeled with a radionuclide

that may be used to follow its distribution or course through

a chemical, physical, or metabolic process.

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Radiation protection principles:

There are several types of radiation that can be emitted from

radioactive substances .

The basic types of radiation are alpha, beta and gamma.

Radiopharmaceuticals administered to patients are usually either

beta or gamma emitting or a combination of both.

Beta radiation doesn't penetrate more than a few millimeters

through tissue.

Gamma emitting radioactive materials can penetrate through

tissue and therefore pose an external radiation hazards.

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There is an important difference between radiation exposure and

radioactive contamination.

Radiation exposure of a person can occur at a distance from

the radioactive materials or source. Radiation exposure

usually occurs as a result of gamma rays being emitted by the

radioactive materials and traveling through air. Gamma rays

that are absorbed by the body can cause harm.

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If a person is contaminated it means that the person has come

into contact with a radioactive substance and that this material

is present on skin, clothing or on objects .

Contamination is hazardous because the radioactive materials

can be inhaled or ingested .

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Figure 1. Calibration of 90Y in a syringe geometry for nuclear medicine applications.

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Pro-Tec II Syringe Shield

Guard Lock PET Syringe Shield

Color Coded Vial Shields

Pro-Tec V Syringe Shield

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Vial Shield (for sulphur colloid preparation

Unit Dose Pig

High Density Lead Glass Vial Shield

Sharps Container Shields

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Services 

Biological Safety

Chemical Safety

EHOS

Fire safety

Radiation safety

Fire safety

Chemical Safety

EHOS

Radiation safety

Biological Safety

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• The regulatory procedures necessary to control

radiopharmaceutical products are in large part determined

by the source of these products and methods of manufacture.

Manufacturing procedures within the scope of these

guidelines include:

The manufacturing of radiopharmaceuticals in centralized

radiopharmacies.

The manufacturing of radiopharmaceuticals in nuclear and

institutes and industrial manufacturers.

The manufacturing of radiopharmaceuticals in positron

emission tomography (PET) centers.

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• Introduction

• Radiopharmacy’s prime responsibility is the preparation of high

quality, radioactive, medicinal products for use in diagnosis and

therapy.  Our products are Medicines and are made under the terms

of a Department of Health Manufacturing “Specials” license.  Our

manufacturing facility in Medical Physics is an aseptic suite designed

to accommodate the handling of radioactive substances, mostly short

lived materials emitting gamma radiation. The manufacturing

facilities are regularly audited by Medicines Control Agency and

Environment Agency Inspectors.

• Facilities