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Mandatory Requirements for Planning and Commissioning of Medical Cyclotron Facility
Address for correspondence: Dr. Rajeev Kumar, Department of Nuclear Medicine, State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Sheikhpura, Patna - 800 014, Bihar, India. E-mail: rajeevraj.aiims@gmail.com
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Received: ,
Accepted: ,
This article was originally published by Wolters Kluwer - Medknow and was migrated to Scientific Scholar after the change of Publisher.
Abstract
Over the last 15 years, there has been substantial growth in the installation of medical cyclotrons. This is mainly due to the increased demand for the production of positron emission tomography radiopharmaceuticals. In every country, there is a regulatory body that regulates the uses of medical cyclotron intending to protect occupational workers, the public, and the environment. It regulates the entire stages of such facilities, which mainly controls regulatory activities such as construction, commissioning, operation, and decommissioning. This article primarily highlights the key practices for planning and installation of a medical cyclotron facility (MCF). It also covers the particular aspects that should be considered in the early stages of project planning and provides information for best practices and challenges. If these aspects are properly addressed, then it ensures the safe operation of the MCF. The texts also elaborate on the necessary requirements for effective planning of the MCF, such as layout and space considerations, workload plan and maximum research capacity of the institute and equipment, shielding requirements, water cooling circuit, storage of radioactive components, management of radioactive waste from medical cyclotron and radiochemistry laboratory, construction and commissioning project management, exhaust system and filtration options, plans for staffing and training, and combination of equipment safety systems and building safety systems.
Keywords
Medical cyclotron facility
nonself-shielded/bunker-type cyclotron
regulatory requirement
self-shielded cyclotron
ventilation
Introduction
There is a paradigm shift in imaging modality after the arrival of medical cyclotron. A new era of nuclear medicine has already been started with positron emission tomography (PET) as it is being used for molecular imaging.[1]
In India, for installation of a medical cyclotron facility (MCF), the user institute must go through the regulatory requirements as mentioned in the Atomic Energy (Radiation Protection) Rules, 2004, and the Atomic Energy Regulatory Board (AERB) safety guide on medical cyclotron facilities. To obtain the necessary regulatory clearance, the user needs to submit the relevant application through the AERB, portal e-Licensing of Radiation Applications (eLORA). Experience has shown that practical design with careful consideration of safety at the very early stage of the project as well as assuring the evolution of the project is vital for the overall safe operation of the facility.[23]
The regulatory body regulates the use of cyclotron-produced radionuclides. It helps to guard the health of radiation workers and protects the public and the environment. The construction, commissioning, operating, and even decommissioning of an MCF requires a license from the regulatory body. It is necessary to ensure that all the safety aspects have been complied with during the commissioning of the project.
Materials and Methods
Stages of clearance of a medical cyclotron facility by the regulatory body
There are various processes for obtaining necessary permissions from regulatory bodies for the operation of an MCF. In India, steps are to be followed while commissioning of new cyclotron facility through eLORA portal online services. Initially, the facility needs to register its institute with a regulatory body either offline or online depending on the country. There are various regulatory processes from the planning of commissioning to the decommissioning of MCF, which applicants have to follow each heading listed below and some points in detail afterward:
Employer: Registration of the institute
Preparation of site layout and elevation drawing
Submission of plan for site and layout approval
Review and approval of plan
Construction of the facility as per approved plans
Appointment of radiation professionals (Nuclear Medicine Physicist cum RSO, Cyclotron Operator, and Radiochemist)
Registration for personal monitoring services and procurement of Thermoluminescent dosimeter (TLD) is a Radiation measuring device, which measure the radiation received by a radiation worker in a 3 months of time period
Nomination of RSO and approval of RSO
Measuring and monitoring equipment: Make model, Sl No., and calibration date
Shielding and remote handling accessories
Equipment permission
Equipment receipt intimation
Permission for quality assurance (QA) and radiation survey
Submission of QA and Radiation Survey Report
Precommissioning inspection
Application for license for operations
Source production permission for clinical uses
Annual Safety Status Report
Periodic QA as per the NEMA
Decommissioning.
Site assessment and approval
The MCF may be installed either in a hospital or in an industrial area. It should be confirmed that there should be no residential or public premises within a radius of 30 m from the site. The applicant is required to provide to the regulatory body the following site-specific information:
Seismic zone as per the IS 1893-1 ‘Criteria for Earthquake Resistant Design of Structures
Maximum level of groundwater and maximum flood level for the past 10 years
Distance of site of installation of MCF from public and nearby residential localities
Documentary evidence from an accredited geotechnical investigation agency that the soil and ground characteristics (e.g., soil profile, stratum, foundation type, soil and rock, elemental analysis of subsoil, and groundwater) will not cause deterioration in the strength and integrity of the structure
Suitable roads to the proposed site
Details of any existing or planned auxiliary facilities such as ammunition dumps, and storage of inflammable and toxic substances within a radius of about 30 m from the proposed cyclotron vault of the MCF.
The regulatory body will inspect the site for necessary approval. The basement of the premises may be an ideal site for the installation of a cyclotron as the earth provides natural and effective shielding. This is again depending on the groundwater level of the soil and the rainy season of that area. Otherwise, the ground floor is a choice for an MCF.
Design and construction approval
Radiation areas and electrical high voltage areas required adequate isolation and access control. The design of the premises should include safe cable routing, segregation of power and signal cables, and provision of barriers to prevent fire.
For obtaining layout, design, and construction approval, the applicant is required to apply along with the layout plan of the facility and Preliminary Safety Assessment Report (PSAR) in the specified format with all supporting documents.
The major components of the PSAR are:
Organizational setup
Detailed system parameters of cyclotron, synthesis, and dispensing units
Design safety features of cyclotron, synthesis, and dispensing units
Zoning and ventilation
Auxiliary facilities
Identification of hazards and their evaluation
Emergency response planning and procedures
QA manual for construction
Physical security measures
Decommissioning manual.
The approval for layout, design, and construction may be granted after a multi-tier review of the PSAR submitted for the installation of the MCF. The regulatory body may inspect the facility while under construction to ensure that the construction is as per the approved design and by the QA manual.
Equipment procurement and equipment receipt intimation
The employer has to apply to the regulatory body for a “No Objection Certificate” (NOC) for procurement of the medical cyclotron. The employer has to provide an intimation of receipt of the equipment within 15 days of its receipt.
Appointment of RSO and staff and procurement of radiation safety instruments
Appointment of staff
An MCF should function with an adequate number of Cyclotron Operator(s), Radiochemist(s), and an RSO [Table 1].
| Staff | Minimum educational qualification |
|---|---|
| Cyclotron operator | DMRIT/M.Sc. Nuclear Medicine/DNMT/BNMT/Diploma in Engineering (Electrical/Mechanical/Instrumentation/Biomedical)/B.Sc. Physics |
| Radiochemist | B.Sc. Chemistry/B. Pham |
| Radiological safety officer | Dip. RP./M. Sc (Medical Physics) or Equivalent/AERB RSO Cyclotron Trained M. Sc Nuclear Medicine/DMRIT |
Procurement of personnel monitors badges
The employer has to procure personnel monitoring badges (i.e., TLD badges) from the agency accredited by the competent authority for all the radiation workers. Pocket dosimeters for the radiation workers may also be procured. It measures the radiation dose received by the radiation worker instantaneously.
Monitoring instruments
The employer has to procure appropriate monitoring instruments for area monitoring (survey meters, contamination monitors, gamma zone monitors, and teletectors) and QA instruments. The requisite instruments must be declared to the regulator and their calibration details must be updated.
Area monitoring
Gamma and neutron radiation area monitoring devices with audio-visual alarms should be provided in all areas where there is a hood of the high radiation field and those areas require constant monitoring. All area monitors should have an appropriate preset alarm. Low- and high-range gamma radiation survey instruments and neutron survey meters should be available at the site. The radiation monitoring instruments should be calibrated periodically. A portable air sampler with an activated charcoal filter paper is required in the facility for the assessment of airborne radioactivity.
Contamination monitoring
In the MCF, large quantities of unsealed sources are handled. There is a high probability that radiation workers handling this radioactivity may get contaminated. Hence, there is a need for a contamination check of radiation before leaving the facility. If contamination is found on clothes and shoes, appropriate decontamination procedures should be followed. It must be stored as contaminated substances safely and appropriately marked. In case of spillage of loose or transferrable contamination on any work surface, the same should be evaluated either by direct monitoring or taking a smear or swipe sample for counting called indirect monitoring.
It is recommended to the all-radiation workers that they should keep one set of clothes at the site of MCF. Periodic surveillance must be done for possible contamination from medical cyclotron, radiochemistry laboratory, and quality control (QC) laboratories.
Precommissioning and trial run permission
The process of commissioning involves making the MCF functional, by ensuring the functioning of the MCF by the approved design specifications. After completion of construction and installation, the applicant approaches the regulatory body for a trial run for commissioning. Trial operations are permitted to evaluate the system performance and radiation level measurement during the precommissioning inspection by the regulator. After successful trial runs, the applicant becomes eligible for obtaining permission for operations.
License and renewal of license
License for the regular operation
For obtaining the license for regular operation, the applicant shall submit the duly filled-in application for a license along with the Final Safety Analysis Report. Based on the review of all safety aspects and inspection by the regulatory body, the license may be granted to operate the unit subject to terms and conditions. The license is granted to the applicant to possess and safely operate the unit with a validity period.
Renewal of license
Renewal of license would be done only after applying for renewal of license. All necessary documents must be attached for the renewal of the license. Application for renewal of license should be submitted at least 3 months before the expiry of license. The validity of the license is usually 5 years.
Decommissioning
When the medical cyclotron is no longer to be used, permission for decommissioning shall be obtained from the regulatory body. The standard operating procedure of decommissioning must be submitted. The induced radioactivity in the cyclotron components and the structures should be considered as radioactive waste. The segregation of waste materials is based on their half-lives. The necessary permission for the disposal of radioactive waste needs to be taken from the regulatory body. The inner wall should be built with about 20–30 cm strippable layer, so we can check it for induced activity. The licensee shall submit a report on the completion of decommissioning, which includes safe disposal of sources and personnel exposures received during decommissioning.
The regulatory requirement for a local supplier in the medical cyclotron
The following parameters have to be fulfilled by the supplier of the medical cyclotron:
Register institute
Supplier authorization: For obtaining supplier authorization, the supplier is required to provide an original equipment manufacturer authorization letter, details of trained manpower, details of radiation monitoring, and QA tools
NOC for the supply of medical cyclotron
Type approval report.
Important safety considerations
The following are examples of safety considerations that could be easy to miss by the proponents, especially at the early stages of the project.
Layout plan and space requirement
The MCF consists of a cyclotron vault and control room, the radiochemistry and radiopharmaceutical production areas, the QC laboratory, radioactivity dispensing, packaging and dispatch areas, the cold-chemistry laboratory areas, and personnel radiation surveillance area (such as the decontamination area). Usually, for medical institutions which are often situated in a dense city, the availability of space is a big issue of concern and needs to be addressed appropriately. The layout must permit the host to accommodate all the compulsory equipment. Furthermore, it should allow easy and safe movement of the workers and materials within the facility and to and from the facility during emergencies. Different vendors are offering different energy for the medical cyclotron, so space requirements also vary accordingly. The layout diagrams of different types of MCF are given in Figures 1-4.
![Floor plan of a typical Type I medical cyclotron facility[2]](/content/210/2024/39/4/img/IJNM-39-243-g001.png)
![Floor plan of a typical Type II medical cyclotron facility housing a self-shielded cyclotron[2]](/content/210/2024/39/4/img/IJNM-39-243-g002.png)
![Floor plan of a typical Type II medical cyclotron facility housing a nonself-shielded/bunker-type cyclotron in a vault with entry through a maze[2]](/content/210/2024/39/4/img/IJNM-39-243-g003.png)
![Floor plan of a typical Type III medical cyclotron facility housing a nonself-shielded/bunker-type cyclotron in a vault with entry through a maze[2]](/content/210/2024/39/4/img/IJNM-39-243-g004.png)
Choice of medical cyclotron
There are always pros and cons while deciding which type of medical cyclotron to install, i.e., self-shielded medical cyclotron or nonshielded/bunker-type medical cyclotron [Table 2]. The self-shielded medical cyclotrons are combined with heavy shielding materials around the medical cyclotron. Additional shielding is needed for nonshielded medical cyclotrons to minimize the radiation levels within the safe limits. In a self-shielded medical cyclotron, the requirement of space and radiation exposure is less but incurs more cost in comparison to a nonshielded medical cyclotron. Hence, in the present scenario, a shielded medical cyclotron is the choice of option from the radiation safety point of view. However, overall, it may be a shielded medical cyclotron or an unshielded medical cyclotron depending on the user.
| Type of MCF | Medical cyclotron proposed to be installed | Particle energy, beam current | RPs proposed to be produced | Usage: In-house and/or distribution |
|---|---|---|---|---|
| I | Self-shielded | H+ beam only up to 20 MeV current ≤150 µA | 18F-FDG | In-house# |
| II | Self-shielded or bunker-type | H+ and/or D+ up to 20 MeV current ≤150 µA | 18F-FDG and other 18F-RPs 13NH3, 11C-RPs 15O-H2O 18F-RPs by electrophilic route | In-house and/or for distribution |
| III | Bunker-type with external beam line | H+ and/or D+ up to 20 MeV current ~150 µA | All those listed in type II above plus 124I - RPs, 64Cu-RPs | In-house and/or for distribution |
| IV | Bunker-type with one or more external beam lines | H+ and/or D+ 20–30 MeV current up to 500 µA | All those listed in type II above plus other SPECT and PET RPs | In-house and/or for distribution |
RPs: Radiopharmaceuticals, PET: Positron emission tomography, SPECT: Single-photon emission computed tomography, MCF: Medical cyclotron facility, FDG 18F- Fluoro-deoxy glucose
Concerning energy, the higher beam energy is preferred so that a wide variety of radioisotopes can be produced. The same is also applicable to the target current; the higher the target current, the higher the activity produced at the end of the bombardment.
Workload and maximum production capacity
At present, several medical cyclotron suppliers are commercially available with increased beam current and energy as mentioned in Table 3. The target current varies with each model of the cyclotron. A single target with a 40-μA beam current on each target would probably be appropriate for in-house production. For outsourcing of PET-radiopharmaceuticals in a large demographic area, a single beam current of 60 μA for each target would be sufficient.[4] The research-oriented project should define its requirements at the beginning and the need to take corrective action for beam current, the number of beamlines, and hours of operation, this would minimize the problem.
| Name of the organization | Energy of the cyclotron (MeV) | Beam current of the cyclotron (µA) | Number of medical cyclotron in India |
|---|---|---|---|
| Siemens | 11 | 40–60 | 7 |
| GE HealthCare | 16.5 | 80 | 11 |
| IBA | 18 | 150 | 5 |
| Sumitomo | 18 | 100 | 1 |
| Advanced Cyclotron Systems Inc. | 19 | 300 | 1 |
IBA: Ion beam applications
The consequence of safety falls in two categories, first: the applicant should establish a safety protocol in which he should include maximum parameters. This safety protocol will be used to design the flawless shielding requirement for the radioactive target areas and the cyclotron bunker. It will also conclude about the maximum radioactivity present in the radioactive target area. This is mainly used for the measurement during target failures and the release of radiation exposure into the facility in case of an emergency accident. Second: during operation, it will tell us about the urgency and requirements. However, the requirements of a QA program and various activity controls are to be defined in the various phases of the project.
Shielding requirements
Medical cyclotron bunkers are constructed with thick concrete walls. This is mandatory to comply with the regulatory requirements as stipulated. The thickness of the wall depends on the model and energy of the medical cyclotron and regulatory authority requirements. The shielding materials include low-Z materials and high-Z materials. The low-Z materials will slow down and absorb neutrons, and high-Z materials will absorb high-energy gamma rays. The shielding material includes high-density concrete, boron carbide, cement for walls, and high-density polyethylene (HDPE) and steel in the door. Shielding is also required during the product transfer from the cyclotron to the radiochemistry module over the tubing system, during the synthesis of PET radiopharmaceuticals in the synthesis modules, and during product transfer from radiochemistry modules to dispensing units. It might be possible that the facility may have beneath-the-floor service channels passing through walls. Usually, they are located in such a way as to avoid direct eye contact from the radiation source to the area outside being protected and to minimize leakage of radiation, especially neutrons. Shielding of the medical cyclotron is to be planned in such a way that maximum neutrons absorb inside the shielding itself. If any radiation exposure is coming from any gap or area, there should be a provision to place some shielding materials. Supplementary shielding is required to reduce the leakage from penetrations.
Water cooling
As the nuclear reaction takes place inside the target area, cooling is a necessary part of the planning. Cooling is done by water and helium cooling jet. In some systems, cooling is done only by a water system. Cooling water is used to cool components mainly targeting system and collimator assembly. The water cooling system has two parts: primary chiller and secondary chiller. The temperature of incoming water should be approximately 10°C.[3] The heat load depends on the target design, beam intensity, and collimation efficiency, and volume of the target materials used. Hence, we should plan our chiller plant in such a way that it should fulfill our requirements. For that selection of the location of the water, the chiller should be done very carefully.
Storage of induced radioactive component
The space for storage of radioactive and induced components of the medical cyclotron varies. This is not only related to the workload and use of the machine but also its design and performance of the machine. If the machine is in more use, it will produce more induced radioactivity. Many components of the medical cyclotron, especially targetry components, and other parts such as Havar foil, collimators, and Carbon Carousels, need to be stored for a long period for radioactive decay. When no shielded space is available in the original design, this becomes a safety concern for the radiation personnel. A location for storage remote from the bunker is not practical and not advisable. The storage of radioactive components in the designated locations will help in radiation protection and also keep the radiation doses of the personnel within the limit of the effective dose prescribed by the regulatory authority.
The cyclotron bunker room might be a very good option for the storage of radioactive components of medical cyclotrons due to their proximity to the cyclotron and the fact that the areas are shielded and rarely occupied. It is stored in the pit which is made and located inside the medical cyclotron vault. The potential high radiation area is the target of the medical cyclotron due to which the radiation workers may receive maximum radiation exposure while accessing the area. Having adequate space to store the components underground or inside a shielded box is always desirable.
Management of radioactive waste from the medical cyclotron and radiochemistry laboratory
Routine waste management is not applicable in MCF and its surroundings. It is mainly dependent on the volume, nature, state, and activity of the potentially radioactive waste, half-life, and the decay rate of the radioactive waste. It is always preferred to store the radioactive waste safely adjacent to the work area. For long-lived radioactive waste, a storage location outside the work area may create unnecessary movements which will give unnecessary radiation to the radiation workers. According to reported recommendations, such type of long-lived radioactive waste is to be kept for 5–20 years depending on irradiation parameters before discarding as exempt waste.[56]
Construction and commissioning of the medical cyclotron facility
Most of the medical cyclotron facilities are located either in an academic institution or in a commercial area. Most of the centers have little or no previous experience with this type of facility. The academic institutions should make a team with improved knowledge and experience. During the installation of MCF, a medical physicist/health physicist and radiation safety officer are very useful and much required. These personnel get the required training and certification from the institute recognized by the regulatory body.
Equipment and building safety system
The MCF includes various monitoring and control functions. They have safety interlocks available in the MCF. These are categorized as administrative safety interlock and machine safety interlock. Machine safety interlocks are radiation interlocks, door interlocks, shield interlocks, water interlocks, circuit interlocks, ventilation interlocks, chiller interlocks, blower interlocks, gaseous system interlocks, and waste gas system interlocks. These safety interlocks ensure the safe operation of the MCF. Apart from this, if any person is trapped inside the cyclotron vault, he may prevent it by searching and clearing operations, scram switches, and audiovisual systems. The ventilation system usually has its backup, monitoring, and control features which are part of the building monitoring. There are many other examples like hot cell monitoring, as well as radiation monitoring systems, electrical safety, fire safety systems, and drainage monitoring included in a safety system. Each of the above-mentioned systems has many safety functions. It can monitor certain parameters and if it is within the prescribed limits which also allows the shutdown of the machine for its safety.
Ventilation and exhaust system
In a medical cyclotron, liquid as well as gaseous PET radioisotopes are produced. During the production of PET radiopharmaceuticals, radioactive vapors are produced. The requirements of the ventilation facility are very much mandatory from a safety point of view. The negative pressure is mandatory for the cyclotron room and radiochemistry hot cell [Table 4]. In the MCF, there are two types of ventilation required, one for the cyclotron and its targets and the other during the processing of the radiopharmaceuticals in the hot cells, biosafety cabinet, laminar flow hood, and fume hoods. The exhaust system should be on during the operations of the medical cyclotron and radiochemistry module. The flow of the exhaust system should be 500 cubic feet/min at the exhaust side.[47] In case of gaseous leakage, just vacant the premises and close all the doors for some time. The day-to-day procedure generates airborne activity from air activation in the medical cyclotron vault and target area near very high-intensity neutron fields. All gaseous waste released from the medical cyclotron vault to the environment has to pass through filter bank assembly, consisting of prefilter, High-efficiency particulate air (HEPA) filter, and activated charcoal filters. Since during the synthesis of 18F-fluorodeoxyglucose (18F-FDG), a large amount of activity is released and may convert into airborne activity, waste gas systems are advisable for the hot cells. All the airborne radioactivity produced during the synthesis of radiopharmaceuticals is stored in the cylinders of waste gas systems under compressed form. After the decay of 24 h, this waste gas is released into the environment through the filter bank system.
| Functional area | Room pressure (Pa) | Number of air changes (h−1) |
|---|---|---|
| General access area | Atmospheric | NA |
| Corridors in MCF | −10 | 2–5 |
| Control room | −10 | 2–5 |
| Packaging room | −10 | 2–5 |
| Personnel airlock for interring R and R | +5 | 10–20 |
| R and R (hot chemistry area) | +20 | 10–20 |
| Hot cell | −50–−100 | >20 |
| QC laboratory | −10 | 5–10 |
| Cyclotron vault | Below −5 | 10–20 |
QC: Quality control, NA: Not available, MCF: Medical cyclotron facility
Staffing and training
For the design and commissioning of an MCF, along with its various components, the appointment of trained and qualified staff is very important. All the staff is appointed by complying with the regulatory requirements. These all requirements must be completed by the employer. It is also essential that all the facility’s essential safety limitations are documented as part of the license application. It is strongly recommended that the employer make the facility operation team right from the start of the MCF. This team will be involved in the regulatory communications as well as the commissioning tests of the facility. There are certain eligibility criteria suggested by the regulatory body as given in Table 1. An extensive preliminary training period is needed for new staff to get familiar with the operation and safety aspects of the MCF so that the team could be able to handle any problem that arises during the operation. The details discussion was also mentioned in the IAEA series document guidelines about the cyclotron-produced radionuclides mainly for 18F-FDG.[8]
Conclusion
Planning and commissioning an MCF for PET radioisotope and PET radiopharmaceutical production require very careful and attentive preparation. Taking into account all safety considerations of several components and characteristics of the MCF, planning is a very important parameter. The regulatory body encourages the safe design and initial consideration of safety features right from the start of the MCF.
Conflicts of interest
There are no conflicts of interest.
Acknowledgment
The author would like to thank the Department of Nuclear Medicine AIIMS, New Delhi, India, and the Health Physics Division, Bhabha Atomic Research Centre, Mumbai, India.
Nil.
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