RADIONUCLIDE
GENERATORS
SMRITI SHARMA
DEPARTMENT OF NUCLEAR MEDICINE, AIIMS
History
1951 - 132Te/132I – BNL
 1960 – 113Sn/113mIn – 393Kev-not suitable for
imaging
 1993 – 99Mo/99mTc, 81Rb/81mKr and 82Sr/82Rb
column generators became commercially
available
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Definition
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A generator is a device containing a longlived parent and a short-lived daughter in a
state of radioactive equilibrium.
 It is constructed on the principle of decay
growth relationship between the long lived
parent radionuclide so that the daughter can
be easily separated
To ´milk´ the´cow´?
Cont...
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Generators thus overcome the problem of
supplying short-lived radio-nuclides to
distant places
GENERATORS
• Principle :Types of Equilibrium
•Characteristics of Ideal Generators System
• Principles of Operation of a 99Mo/99mTc
Generator
•Other generators
• Quality Control of 99Mo/99mTc Generator
• Regulations and Standards for generator use
Generator Principles
Mathematical Relationships

Bateman described mathematically the
relationship between parent and daughter activity
 The characteristics of any generator system are
based on the decay constants of the two isotopes
involved
 The relationship of these decay constants
determines the type of equilibrium that can be
attained for a given parent-daughter pair
Successive Decay and Parent/Daughter
Equilibrium
Parent--lp----> daughter ---ld----> daughter decays
Ap(t) = Ap (0) e-lpt
• Ad(t)=Ap (0)[ld/ ld- lp ] (e-lpt - e-ldt) + Ad(0) e-ldt
•If lp << ld (100-1000 times)
Ad(t)=Ap (0) (1 - e-ldt)
Secular equilibrium
•If lp < ld (10 to 50 times)
Ad(t)=Ap (0)[ld/ ld- lp ] e-lpt
Transient equilibrium
Parent activity remains nearly constant
Activity of daughter increases until it becomes equal to that of
the parent
Activity and decay rate of daughter and parent are same
Activity of Daughter becomes higher than that of the parent
and decay with the same rate.
Yield from column generator
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A99mTc
=
0.956 (A99Mo)t
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(A99Mo)t
=
(A99Mo)0* e-0.0103t
Desirable Characteristics
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High separation efficiency of daughter radionuclide
High selectivity in separation (high radio-nuclide purity)
High radiochemical and chemical purity
High yield during each elution
Simple and rapid operation at user end
Radiological safety to operate
Continuous availability of parent radionuclide
Easily Transportable
Daughter with Ideal Half life and Gamma Energy
Chemistry of the Daughter Allows Hospital preparation
Production of Parent Radionuclide
Primary Source:
– * Reactor
– * Cyclotron
Nuclear Fission Reactor
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Fission products are generated from rods of 235U inserted into reactor
core.
Chemical separation of 99Mo, 131I, 133Xe is readily possible from rod
material
235U(n,f)99Mo, fission yield 6.1%
Nuclear Reactors
• AX (n, g) A+1X
• 98Mo (n, g ) 99Mo------> 99mTc
• Starting Material and Products have the Same Chemical Identity.
• Low Specific Activity Radionuclides
Cyclotrons
• Example : 68Zn (p,2n) 67Ga
• Starting Material & Product Have Different
Chemical Identity
• Radionuclides with High Specific Activity
• Expensive
• Radionuclides Decay by b + or EC
N. Reactor

n bombardment
 (n,g), (n,f)
 n excess
 B- decay
 Long T1/2 daughter
 (n,g) low specific activity
 (n,f) high specific activity
 economical
Cyclotron
charged particle
(p,n), (d,n)
p excess
B+, EC
short T1/2
high
Expensive
Radionuclide Separation techniques

Differences in physical state
 Differences in chemical properties
Solvent extraction (based on different
solubilities)
– Chromatography(based on differing affinities
for an ion-exchange resin)
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Gel generator
Sublimation (based on differing volatilities)
Solvent extraction generator
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Parent
 Parent radiochemical
 Daughter
 Organic solvent
 Aqueous solvent
99Mo
99MoO499mTcO4MEK
KOH
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The separation is based on selective extraction of
Tco4 into methyethyl ketone from aqueous
alkaline solution of sodium molybdate.
Mixing of aqueous and organic phase.
 Purification of organic medium by passing through
alumina column.
 Evaporation of organic phase.
 Residue is reconstituted with physiological saline
and sterilized to obtain Tc in the form of Tco4suitable for I.V use.
Advantage

Ability to utilize relatively inexpensive low
specific activity 99Mo.
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High extraction efficiency.
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High radionuclide purity.
Drawback
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It is a time consuming separation
procedure.
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It introduce operator dependent error in the
form of reduced radiochemical purity.
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Hazard of handling inflammable solvent
Column generator
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99Mo/99mTc Generator
• Parent: 99Mo as molybdate (99MoO4-2)
• Daughter:99mTc as pertechnetate(99mTcO4-1)
• Adsorbent Material: Alumina (aluminum oxide,
Al2O3)
• Eluent: saline (0.9% NaCl)
• Eluate: 99mTcO4-1
99Mo
Half-life: 67 hr.
• Decays by b decay 1.2 Mev(82%) and g - emission,
gamma: 740, 780 keV.
• High affinity to alumina compared to 99mTc.
Setup
Advantage

Ease of operation.
 High elution efficiency.
 High purity.
 High radioactive concentration.
Disadvantage
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Cost of these generator are relatively high
mainly due to the need for fission produced
99Mo.
 Difficult to manage the toxic fission product
waste generated.
Column Gel Generator
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Parent
 Parent radiochemical
 Daughter
 Adsorbent material
 Eluate
 Technical challenges
99Mo
ZrMo gel
99mTc
Gel + Alumina
99mTcO 4
Gel formation
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Moly trioxide is irradiated and then dissolved in
basic ammonia.
 The resultant solution is then added to an aqueous
zirconium to obtain zirconium moly precipitate in
the form of gel like matrix.the matrix is then
separated from the solution by filtration
,evaporation ,air dried and sized for use in the
generator.
 It provides more 99Mo medium then prior
alumina adsorption.
Disadvantage
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This systems require significant handling and
processing of irradiated materials, including
dissolution, precipitation, filtration, drying, gel
fragmentation and column packing steps, all
occurring after irradiation of the molybdenum
trioxide.
 These processing steps necessitate the use of
cumbersome shielded processing equipment,
result in relatively high manufacturing costs and
pose significant potential safety risks
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In order to overcome some of the problems in
connection with the production of 99m Tc, all the
steps are avoided by directly irradiating
zirconium molybdate instead of molybdenum
trioxide
 The direct irradiation of zirconium molybdate
resulted in the production of radioactive
contaminants unacceptable for clinical therapeutic
or diagnostic applications, including 97 Zr, 95 Zr,
175 Hf, 181 Hf, and 24 Na.
Sublimation generator
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Parent
 Parent radiochemical
 Daughter
 Boiling point 99mTc
 Melting point 99Mo
 Boiling point 99Mo
99Mo
99MoO
3
99mTc
2O7
310.60C
7950C
11500C
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Brief introduction about other radionuclide
generators
113Sn/113In
Generator
 113
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sn half life=117d,EC
113In half life=100 min,IT,393KEV
Adsorbed on zirconium oxide column
Eluted with 0.05N HCl.
Elution efficiency 80%.
81Rb/81Kr
 81
Generator
Rb half life=4.6hr,Ec
 81 kr half life=13s,IT,190KEV
 Adsorbed on AG 50 resin.
 Eluted with air.
• Used for lung ventilation.
• Elution efficiency 70-80%
68Ge/68Ga
 68
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Generator
Ge half life=271 days
68 Ga half life=68min,
Adsorbed on tin dioxide/alumina
Eluent 1N HCl
Nowadays we use Tio2,eluted with 0.1N Hcl
Yield of gallium-75-80%
Shelf life 1 year
82Sr/82Rb
Generator
 82Srhalf life=25dys,Ec
 82 Rb half life=75s,B+
 Adsorbed in sno2 column.
 Eluted with 0.9%Nacl solution.
 Positron generator
 Used for cardiac studies.
 Sodium nonatitanate.Eluted with 1M Nacl.
 Life span 3-4 months.alumina column requires
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periodical checking of sterility , apyrogenicity and
breakthrough levels.
Elution efficiency 85-95%
188Tungsten/188Rhenium
generator
188W
188Re
half life=69.4 days,B-,349kev
half life=16.9 hr,B-,155 kev gamma photon(15%)
Adsorbed on alumina or zirconium oxide.
eluted with NaCl solution.
Used to label several tumor-specific antibodies.
The parent radionuclide 188W, formed by the double neutron
capture on 186W, by β-decay produces 188Re:
186W(n,g)187W(n,g) → 188Re
Potential problem and trouble shooting
problem
Possible cause
Trouble shooting
Absent or reduced elute
volume
Vial lost partial or complete
vacuum
Fluid line blocked.
Eluting needle don’t pierce
septum.
Elution needle blocked.
Use fresh evacuated vial.
Lower than expected
activity
May occur in 1st day of
elution. long time gaps in
between elution.
Elute repeatedly
99Mobreak through
close to specified limit
Faulty generator/column
damaged
Elute column for 5-6 times,
record 99Mo activity for ach
elution if it drops to within
acceptable limit ,column is ok if
not contact manufacturer.
Try larger evacuated vial.
Try another needle if feasible.
Replace needle if possible.
REGULATIONS AND
STANDARDS FOR
GENERATOR USE
pH
4.5-7.5
Sterility
and Apyrogenicity
Radiation Safety concerns
– Possession and use of radionuclide generators
are restricted to licensed persons from AERB
– A number of regulations dealing with receipt,
storage and disposal of generators have been
developed by AERB
Radiation Safety concerns
– Receipt
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Use gloves to prevent hand contamination
Inspect package for any damage
Monitor external exposures rates at 1m distance
Check for surface contamination
– Operation
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Wear TLD badges and gloves
Use syringe shields while handling high activities
Perform wipe testing regularly
Work behind L-bench
Radiation Safety concerns
– Storage
 HVL for 99Mo (7 mm)
 Below 200mCi generator self shielding is adequate
 Keep behind lead bricks/shielded
– Disposal
 Decay in storage
– Dismantle the oldest generator first
– Log the generator date and disposal date
– Remove or deface the radiation labels on generator shield
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