Radio Pharmaceuticals
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Transcript of Radio Pharmaceuticals
RadiopharmaceuticalsDesign and safety handling
Nahla S. Barakat, Ph.DDept. of Pharmaceutics
College of PharmacyKing Saud University
1429/2008
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
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 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.
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.
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
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
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 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.
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 (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).
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.
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 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.
(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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 .
Figure 1. Calibration of 90Y in a syringe geometry for nuclear medicine applications.
Pro-Tec II Syringe Shield
Guard Lock PET Syringe Shield
Color Coded Vial Shields
Pro-Tec V Syringe Shield
Vial Shield (for sulphur colloid preparation
Unit Dose Pig
High Density Lead Glass Vial Shield
Sharps Container Shields
Services
Biological Safety
Chemical Safety
EHOS
Fire safety
Radiation safety
Fire safety
Chemical Safety
EHOS
Radiation safety
Biological Safety
• 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.
• 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