Radionuclide Generators
A Radionuclide Generator is the major
source of short–lived radionuclides used in Nuclear Medicine. In a radionuclide
generator, a longer–lived radionuclide is called the parent decay while the shorter–lived
radionuclide is called the daughter. The daughter can be removed periodically
as it is replenished by decay of the parent.
Examples of Parent–Daughter Systems
are:
1. Germanium–68
/ Gallium–68
2. Rubidium–81
/ Krypton–81
3. Molybdenum–99
/ Technetium–99
Molybdenum–99
/ Technetium–99m Generator
Parts of a 99Mo/99mTc
Generator
1. Aluminum
trioxide (alumina) column – this is where the parent radionuclide, 99Mo
is absorbed.
2. Porous
glass – holds the alumina in place but allows saline to pass through it.
99mTc is removed
or eluted from the column when a sterile, evacuated vial is in placed at the
opposite end of the saline eluant. The vacuum in the collection vial causes the
saline to be pulled through the alumina column, which removes the loosely bound
99mTc. Due to the different chemical properties of the parent and
the daughter, 99Mo remains on the column while 99mTc is
collected as the generator eluate in the form of [99mTc] sodium
pertechnetate.
Types of 99Mo/99mTc
Generator
1. Wet
column generator
– contains a supply of sterile saline within the generator itself. To elute
this type of generator, the technologist chooses the appropriate size
collection vial to obtain the volume and activity concentration desired.
Because no air follows the saline as it flows over the column, the column
remains wet.
2. Dry
column Generator
– requires that saline, provided by the generator manufacturer, is placed on
the charging port, a needle connected to tubing that carries the saline to the
alumina column. An evacuated vial is the place onto the needle on the
collection port. The vacuum pulls the saline over the column, removing the 99mTc
activity. Using an evacuated vial with a volume larger than the saline volume
causes air to be pulled over the column, completely removing any saline.
Maintenance of
Generators
1. The
septa of eluate and saline vials should be swabbed with alcohol
2. Needles
used to deliver saline or to collect the eluate should be replaced with new,
sterile needles following each elution.
3. Millipore
filters are oftentimes present to ensure sterility of the generator
Generator yields
All 99Mo/99mTc
generators contain 99Mo from the fission of Uranium–235 which has a
high specific gravity. Specific gravity refers to the amount of radioactivity
per unit mass of a radionuclide or radiopharmaceutical and is expressed in such
units as millicuries per milligram (mCi/mg), megabecquerels per milligram
(MBq/mg), curies per mole (Ci/mole) or gigabecquerels per mole (GBq/mole).
A simplified, useful rule of thumb
when elution is performed only once every 24 hours is that the eluate yield
will be 80% of the previous yield.
Percent of
Technetium–99m activity present in generator column at selected times following
Elution
Time
since elution 99mTc
activity
(hour) (%99Mo activity)
1 9.4
2 18
3 26
4 32
5 39
6 44
7 49
8 54
9 58
10 61
11 65
12 68
18 80
24 87
Problems from Elution
1. Mechanical
problem such as an air leak in the tubing may prevent the saline from being
drawn out of the column into collection vial.
2. “Channeling”
of the alumina column causes only a portion of the column to be exposed to
saline, leaving 99mTc on that part of the column not washed with
eluant.
3. Chemical
reduction of 99mTc from +7 valence state to other reduced states
occurs when reducing agents are formed by the radiolysis of water. The reduced 99mTc
remains bound onto the column and is not eluted.
Eluate assay and Quality
Control
1. Concentration
of eluate
Concentration = Total
99mTc activity (mCi)
Elution volume (ml)
2. Molybdenum–99
content
The appearance
of 99Mo in generator eluate is called “molybdenum (or moly)
breakthrough” which is considered a radionuclide impurity. When administered to
patients, 99Mo is taken up by the parenchymal cells of the liver and
delivers an unnecessary radiation dose to that organ.
The NRC states
that the amount of 99Mo in 99mTc generator eluates may
not exceed 0.15 µCi per 1 mCi 99mTc.
3. Lead
shield (or Moly Shield) Method
A lead
container is used, which is designed to absorb Tc99m photons (140 keV) as well
as permit the passage of higher energy (740, 780 keV) Mo99 photons. The
generator eluate is placed in the moly shield and assayed in a dose calibrator
to determine the Mo99 content. Sometimes it is necessary to apply a correction
factor to the Mo99 assay. Instructions supplied with the molyshield should be consulted.
To determine the amount of Mo99 contamination in the eluate, divide the Mo99
assay result by the total number if millicuries of Tc99m in the eluate measured
with the dose calibrator.
99Mo breakthrough = µCi 99Mo
mCi
99mTc
4. Mock
Moly method
This method
compares the unknown 99Mo to that of a cesium–137 reference standard of known
activity. A well–type scintillation counter is used. The pulse–height analyzer
window is set to accept counts within a range of 600 – 1000 keV which will
include the principle photon of 99Mo (740, 780 keV) and 137 Cs (662 keV).
µCi 99Mo = net
counts 99mTc eluate x µCi137Cs standard
net counts 137Cs
standard
5. Aluminum
Ion content
Aluminum ions
from the generator column appearing in the 99mTc eluate are a
chemical impurity. Such impurities can affect the biodistribution of
radiopharmaceutical. The established USP Al+3 concentration limit is
10 µg Al+3/ml eluate is not exceeded.
Preparation of Technetium–99m
radiopharmaceuticals
1. Technetium–99m–sodium
pertechnetate eluted from a 99Mo/99mTc generator is combined with the
appropriate kit reagent to form a tissue–specific compound after only a brief
incubation period.
2. Most
of 99mTc–labeled compounds with the exception of 99mTc
colloid, are prepared with chemically reduced 99mTc, a more active
form of Technetium. For this reason, 99mTc labeling is accomplished
in the presence of stannous chloride, a reducing agent. Most commercially
available radiopharmaceutical preparation already has stannous chloride
incorporated in the compound.
The stannous
ion (Sn+2) reduces the valence state of the technetium in the
pertechnetate ion from +7 to +4 or another reduced valence state. The reduced 99mTc
(IV) is a more reactive species, capable of combining with a variety of
compounds.
Radiopharmaceutical
with specific preparation
a. Technetium–99m–MAA
is prepared with reduced 99mTc however the number of particles to be
administered to the patient should be considered. The recommended number of
particles is 200k to 700k particles
If too few
particles are administered, the perfusion lung image may be technically
unsatisfactory and may have the appearance of decreased uptake.
As 99mTc
decays, the number of radioactive particles decreases, while the total number
of particles in a milliliter remains constant. Therefore, as time passes, more
particles must be administered to obtain the same amount of activity.
b. Technetium–99m–sulfur
colloid does not require stannous chloride for preparation. Instead, it
contains an acid, sodium thiosulfate, a buffer and gelatin.
Radiopharmaceutical Quality
Control
1. 99mTc is present
in three different chemical forms
a. Bound
99mTc agent – the desired form needed for examination
b. Unbound
(free) 99Tc pertechnetate – can be visualized on images as increased
tracer concentration in the stomach, thyroid and salivary glands.
c. Hydrolyzed,
reduced 99mTc (HR–Tc) – is indicated through uptake in the
reticuloendothelial system, especially liver.
Technetium–99m–pertechnetate
and HR–Tc are radiochemical impurities
Radiochemical
purity is defined as the fraction of total radioactivity present in its desired
chemical form.
2. Radiochromatography
– in this method, a drop of the radiopharmaceutical to be tested is placed at a
point called the origin, near one end of the paper strip. The strip is then
immersed into a solvent. By capillary action, the solvent travels up the strip
carrying with it the soluble components in the sample.
Insoluble
components remain at the origin. As the solvent nears the top of the strip, the
strip is removed, dried and cut in half. Each half is counted in a well counter
or dose calibrator and the labelling or tagging efficiency, the fraction of
radioactivity incorporated into the desired radiolabeled agent.
%
Radiochemical impurity = cpm in Part A x 100%
cpm
in Part A + cpm part B
Labeling
efficiency = 100% – [(%free 99mTc) pertechnetate + HR–99mTc]
The Rf
value refers to the distance the component travels from the origin compared to
the distance traveled by the solvent.
Rf
value = distance component travels from origin
distance of
solvent front from origin
Unit Dose Preparation
1. Radionuclide
and chemical form of radiopharmaceutical. A radionuclide such as 99mTc may be
tagged to a variety of chemical compounds so care should be taken to choose the
correct radiopharmaceuticals for a given nuclear medicine procedure.
2. Expiration
time/date. The time at which the radiopharmaceutical should no longer be
administered to patient to patients.
3. Volume
(in ml). The total amount of liquid in the vial
4. Total
activity. The total amount of radioactivity present in the vial at the time of
assay or calibration.
5. Concentration.
The amount of activity per unit volume at the time of assay or calibration.
Concentration is obtained by dividing the total activity in the vial by the
total volume.
Concentration = Total
activity
Total
volume
6. Assay
or calibration time/date. The time and / or date when the total activity and
concentration were determined
7. Specific
gravity. The amount of activity per unit mass of a radionuclide or
radiopharmaceutical. Do not confuse specific gravity with concentration. A
specific gravity may not appear on all radiopharmaceutical labels.
8. Lot
number. A number assigned by the manufacturer to each batch of
radiopharmaceutical. The number can be used to trace problems associated with
the radiopharmaceutical.
9. For
adults, the standard dose range is already predetermined. For pediatric
patients, they should receive at least 62% of the recommended adult dose or any
of the following formula for computation
a. Clark’s
rule weight in lbs.
x adult dose
150 lbs.
b. Webster’s
rule age (yr) +1 x adult
dose
age
+ 7
c. Young’s
rule age (yr) x adult
dose
age
+ 12
10. Initial
radiopharmaceutical concentration is decay – corrected for the time of
administration and the volume to be administered.
Co x DF = Ct
Co = initial
concentration
DF = decay factor
Ct = concentration
at time
11. Determine
the volume to be administered
Patient dose = volume
to be administered
Ct
Example:
A technologist
needs 3.5 mCi of Thallous chloride to perform mycordial imaging on September 6.
If the concentration of the radiopharmaceutical is 2 mCi/ml on September 8,
what volume should be administered to the patient?
Co x DF = Ct
Co = Ct/DF
= 2 mCi / ml
0.634
= 3.2 mCi / ml
Patient dose = volume
to be administered
Co
3.5 mCi = 1.1 ml
3.2 mCi / ml
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