Safe workplace with effective shielding and

It is imperative that radiopharmaceutical laboratory design should be focused on local regulatory agency requirements and personnel safety. The level of shielding and automation depends on the workload, resources and

available expertise. There are several options to minimize personnel exposure in a PET radiochemistry laboratory. To achieve effective shielding, the practical and most effective means to handle PET radioisotopes safely and to protect laboratory personnel from radiation is to use 60–75 mm thick lead lining.

Therefore, the simplest way to provide this added protection is to enclose all work areas with lead walls. Unlike a decade ago, there are multiple choices for the safe and effective handling of PET isotopes.

5.3.1. Lead lined hoods

A primitive but economical and practical option for remote handling of radioisotopes is the lead lined fume hood or lead cave (Fig. 5). The reagents are added remotely to the reaction vessel from behind the lead wall using syringes and valves controlled by push buttons (on the right hand side of the sash in Fig. 5).

FIG. 5. A lead lined hood: a fume hood converted to a lead lined cave for remote

The work area is lined with lead bricks and the radiochemistry synthesis apparatus is placed inside this lead lined area. The reagents can be added from outside using syringes and valves that are located on the outside of the lead lined area without entering the radiation field.

The lead glass windows are an aid to monitoring the reaction without having to lean over the lead wall. These lead caves are suitable for housing computer controlled synthesis boxes or for using a remotely controlled procedure where minimal or no operator interventions are necessary inside the work area. The use of these lead lined hoods is well suited for developmental work using small amounts of radioactivity, because manual access to the inside is feasible. In addition, maximum quantities of radioactivity in one of these lead caves should be restricted, as it is not completely shielded on all sides with lead.

5.3.2. Hot cells

The next option to create a safe workplace is the use of hot cells (Fig. 6).

The hot cell concept is similar to that described for the lead cave. The hot cells are primarily lead caves but provide lead shielding in all six directions. The access to the inside work area is limited to the front and sides of the cells through panels or doors that are closed during operation. As these cells are shielded at the top and bottom, radiation exposure within and around the radiochemistry laboratories is significantly reduced. The hot cells provide access to the inside space for preparation work before synthesis takes place and for cleanup after use. During the synthesis time, all doors and side panels are closed, to minimize and/or eliminate laboratory radiation exposure and to ensure that the inside environment can be controlled. The operator uses robotic arms (manipulators) from outside the cell for safe and effective handling of radiopharmaceuticals. These hot cells are well suited for installing synthesis boxes that can be operated by automated procedures.

As can be seen in Figs 6 and 7, operators can reach the reaction vials and other items that are located inside the cell remotely using the arms located outside the cell and without encountering any radiation exposure.

Figure 8 shows a set of two hot cells, with robotic arms providing support for manual interaction without jeopardizing safety. Once the finished radiopharmaceutical is ready, the final product can be either delivered to a side drawer lined with lead or accessed from a side panel, depending on the model purchased, without opening the hot cell doors. It is advisable to wait for the radioactivity to decay before opening the hot cell doors for cleanup or for setting it up for reuse. There are several manufacturers that sell hot cells inter-nationally. Hot cells require a large investment, and it is therefore important to

match the options that a particular vendor offers and the requirements for safe and effective operation of the radiopharmaceutical manufacturing site before choosing a hot cell vendor. It should not be assumed that all hot cell vendors would provide the same options, designs and accessories.

FIG. 6. An operator working on a hot cell with robotic arms.

FIG. 7. Inside view of a hot cell through the hot cell window in the door. The inside part of the robotic arm is reaching for the reaction vessel, while the operator is working with the manipulators outside.

A large number of laboratories acquire remote controlled arms (manipulators) to help remote handling of radioactivity within the hot cell (Figs 6–8). If semi-automated synthesis or manual interventions are anticipated during the radiosynthesis, installation of these manipulators will add safety as well as the option to perform manual operations in the process. This option allows safe handling of large quantities of radioactivity while maintaining safety. As shown in Figs 6 and 7, the operator works with manipulator arms from outside the hot cell to simulate manual operations.

The arms aid in moving and transferring radioactive materials, as well as activating the next process as performed during manual processing. Several vendors manufacture manipulators that can be used in hot cells, and most of them export these items internationally. Most hot cell vendors could retrofit manipulators in existing hot cells. If deferring the manipulator purchase at the time of hot cell purchase, it is advisable to opt for manipulator hole cut-out plugs. The manufacturer will make the housing insert for manipulators and will cover these with lead plugs to retain their integrity while providing the flexibility to install manipulators by removing these plugs during future refits.

Hot cell manufacturers have responded to ever increasing regulatory requirements for the production of safe and effective radiopharmaceuticals. A stringent pharmaceutical QC criterion can be met with the high energy particulate airfilter (HEPA) option available with some hot cells. Once the radiopharmaceutical has been prepared and collected in a sterile vial under a

FIG. 8. A set of two hot cells with robotic arms.

sterile environment, further doses can be drawn using the dose drawing options available from certain hot cell manufacturers.

5.4. AUTOMATED AND REMOTE CONTROLLED SYNTHESIS