Authorization and Inspection of Cyclotron Facilities Hot cells
and associated systems for the production of
radiopharmaceuticals
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Authorization and Inspection of Cyclotron Facilities To be
familiar with the equipment, facilities and security systems, used
in the synthesis of radiopharmaceuticals labeled with positron
emitters. Identify the applicable radiation protection
requirements.
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Authorization and Inspection of Cyclotron Facilities 1.
Transfer from the cyclotron. 2. What is a hot cell? 3.
Characteristics of hot cells. 4. Special features of hot minicells.
5. Synthesis modules. 6. FDG production.
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Authorization and Inspection of Cyclotron Facilities After the
bombardment in the cyclotron, the radionuclide produced is
immediately and automatically transferred to the hot cells located
in the radiopharmacy laboratory. Cyclotron Hot Cells Radiopharmacy
(synthesis) Transfer It is performed through capillary tubes (eg
Teflon and PEEK) through a pneumatic transfer gas push as, for
example, He.
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Authorization and Inspection of Cyclotron Facilities
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Transfer line for liquid target ( 18 F) Transfer lines are
placed in accessible underground ducts, in a depth between 30 to 40
cm and must be shielded (concrete slabs or several lead plates).
Transfer tubes emerge from the shield as close as possible to the
destination (hot cell). For small distances, transfer can take less
than 2 minutes, including the time required to purge the line.
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Authorization and Inspection of Cyclotron Facilities
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Transfer lines are inserted, for protection, inside other
connection tubes (semirigid) of larger diameter. The high
activities carried inside the tubes can cause degradation,
enhancing activity absorption in its walls, so they have to be
replaced periodically (depending on activity produced and the
frequency of use).
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Authorization and Inspection of Cyclotron Facilities The length
of the transfer line must be as short as possible and in accordance
with the regulations, so that: It must be ensured a safe and quick
transfer (ej: O 15, T 1/2 = 2.05 min). A reduction in the losses of
the activity on walls and the probability of damage in line
(obstruction or rupture) is guaranteed. The lines lenght as short
as possible, as well as the associated costs with shielding.
Synthesis labs adjacent to the cyclotron bunker
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Authorization and Inspection of Cyclotron Facilities
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Qu es una celda caliente? A technological mean of defense, used
to manipulate and process radioactive materials. They can be
arranged in series, in blocks or individually. What is a hot
cell?
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Authorization and Inspection of Cyclotron Facilities Allow the
manipulation and process of cyclotron produced radionuclides, using
remote means and/or dispensing synthesis and modules (automatic or
semiautomatic) that ensure higher safety and accuracy in
radiochemical processing and fractionation. Ensure the protection
of operators, facilities and environment, to shield the high level
of radiation and prevent the uncontrolled spread of radioactive
contamination. Guarantee, by applying the requirements of Good
Manufacturing Practices (GMP), the synthesis of
radiopharmaceuticals in an aseptic environment.
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Authorization and Inspection of Cyclotron Facilities
Structurally constituted by a steel frame supporting the shield.
The cells have in their interior a watertight enclosure, made by
stainless steel floor and PVC or acrylic walls. Design based on the
principle that the shielding is more economical and more effective
if it is as close as possible to the radiation source.
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Authorization and Inspection of Cyclotron Facilities To reduce
exposure time, the hot cells have some devices for simple
maintenance procedures. There are many different cells and remote
handling devices, however, the best choice depends on what is
expected.
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Authorization and Inspection of Cyclotron Facilities The hot
cells have different systems and safety devices: ventilation,
automatic alarms, compressed air, vacuum, radiation detectors,
gauges, etc.
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Authorization and Inspection of Cyclotron Facilities Inner
surfaces of polished stainless steel of high quality (grade 316 by
its resistance to corrosion) and acrylic or Lucite (transparent
plastic that replaces glass). Automatic, semiautomatic systems or
telemanipulators for operations.
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Authorization and Inspection of Cyclotron Facilities Panel
command
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Authorization and Inspection of Cyclotron Facilities Interior
surfaces are smooth, impervious, continuous, without right angles
at junctions. Work surfaces with tray structure (with raised edges)
to prevent spills. Permanent installation of components that can
not be cleaned properly, should be avoided. Service ducts
(electricity, liquids, gases) have seals and penetrate the
shielding in a curved form (S-shaped) to prevent radiation
streaming.
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Authorization and Inspection of Cyclotron Facilities Scheme of
a conventional cell 1.Control panel. 2.Ionization chamber. 3.Leaded
glass window. 4.Lighting system. 5.Sealed Enclosure. 6.Lead
shielding. 7.Steel cover. 8.Transfer system access. 9.Liquid waste
liner vessel. 10.Solid waste liner vessel. 11.Telemanipulator.
12.Radiation Detector.
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Authorization and Inspection of Cyclotron Facilities Accesses
For intervention tasks, maintenance, cleaning or replacement of
devices in sealed enclosures, gloves, pneumatically operated
guillotine doors or other access are needed. The cells will be
sealed in accordance with internationally accepted standards.
Sliding doors
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Authorization and Inspection of Cyclotron Facilities The
introduction of objects and reagents, the extraction of the
products and waste disposal systems require sanitary access systems
(SAS) maintaining reliable and safe aseptic conditions inside the
hot cell.
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Authorization and Inspection of Cyclotron Facilities Central
sliding door. Different designs of hot cells openings Minicells
with front access. Vertical front access with
telemanipulators.
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Authorization and Inspection of Cyclotron Facilities Concrete,
lead bricks lead with antimony between 4 -7% to increase its
mechanical strength, leaded glass, steel and depleted uranium are
used as shielding, supported by rigid steel frames coated with
epoxy paint. The thickness of the shielding must be calculated on
the basis of type and energy of radiation and the activity to be
manipulated. the integrity of the shielding During the
commissioning of a new hot cell, the integrity of the shielding
must be verified!
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Authorization and Inspection of Cyclotron Facilities
Transparent leaded glass windows, conveniently placed on the wall,
are used to observe the interior of the cells and to make possible
visual control of processes and the radiation protection of the
operators. (10 cm lead glass = 5 cm of Pb)
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Authorization and Inspection of Cyclotron Facilities Remote
handling There is commercial availability of two basic designs (by
different suppliers) for remote manipulation of materials or
equipment within the hot cells: Manipulators Must be installed with
precision, properly adjusted and tight.
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Authorization and Inspection of Cyclotron Facilities Ball joint
for the telemanipulator Length of ~ 1 m mounted on shielded ball
joints placed on the shielded wall. With interchangeable edge,
allows the grip replace without the necessity of removing the
enclosure.
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Authorization and Inspection of Cyclotron Facilities Are used
if the wall thickness of the shield is greater than 100 to 150 mm.
Recommended if operations are complicated, sensitive or require
greater precision. Telemanipulators
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Authorization and Inspection of Cyclotron Facilities Must
comply with the requirements of Good Manufacturing Practices. To
prevent radioactive spreading, the enclosure should be kept in
depression. To prevent the introduction of powder and the spread of
any contaminated particles, HEPA (High Efficiency Particulate
Arresting) filters must be installed (inlet and outlet). Activated
carbon filters at the exit, for gases. Ventilation
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Authorization and Inspection of Cyclotron Facilities Specially
designed for PET technology. Used for automated synthesis of PET
pharmaceuticals and dispensing into vials and syringes. Completely
closed with controlled airflow, double door (exterior is shielding,
insulation inside). Minicells
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Authorization and Inspection of Cyclotron Facilities Shielding
of lead - 75 mm and more. Filtration: HEPA and activated carbon.
Interlocks: opening and transfer. Aseptic conditions (GMP). Simple
or double cells, with independent operation.
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Authorization and Inspection of Cyclotron Facilities Autoclave
with capacity for dozens of vials. Radiation detectors inside and
outside. Manometer to measure filter clogging. Pressure gauge for
measuring the pressure difference between the interior of the cell
and the laboratory.
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Authorization and Inspection of Cyclotron Facilities The small
half-life of the produced radionuclides and the energy of the
annihilation photons lead to the need of attention directed to both
the processing and handling, according to regulations. Synthesis
modules The chemical synthesis shall be fast, reliable,
reproducible, GMP compliant, radiologically safe, automatic and
remote.
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Authorization and Inspection of Cyclotron Facilities Equipment
where all processes (chemical in nature) necessary for the
production of PET radiopharmaceuticals are performed. They operate
automatically and through a software control, which monitors the
entire process through a computer.
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Authorization and Inspection of Cyclotron Facilities Since the
final product is injectable, it must be sterile and pyrogen free.
The synthesis module has high technological complexity. Use of
disposable sets of reagents.
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Authorization and Inspection of Cyclotron Facilities Before
each synthesis the cell has to be cleaned and the synthesis module
reloaded with the reagents necessary for the process. Use of
disposable kits or integrated cassettes (preloaded with
pharmaceutical reagents) which are positioned or adjusted in a
straightforward way, avoids the use of manual measurements of
reagents, which suppresses the risk of human error.
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Authorization and Inspection of Cyclotron Facilities The F18 in
the synthesis module reacts in a series of steps with other
chemical reagents, and fluorodeoxyglucose (FDG) is produced
(typically in 1 hour). Subsequently the material is transferred to
a dispensing hot cell where, with the help of an automatic
dispenser, it proceeds to fill the vials to provide, under aseptic
conditions, the final sterilization by autoclaving.
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Authorization and Inspection of Cyclotron Facilities The
activity is verified with the activimeter. The vials are placed in
appropriated containers. Later they are packaged for
distribution.
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Authorization and Inspection of Cyclotron Facilities Quality
control Sampling and strict quality controls to ensure the quality
of the product to be administered to patients. Laminar flow