Assessment of occupational exposure from shielded and unshielded syringes for clinically relevant positron emission tomography (PET) isotopes—a Monte Carlo approach using EGSnrc

¹⁸F has been the most widely used radionuclide in positron emission tomography (PET) facilities over the last few decades. However, increased interest in novel PET tracers, theranostics and immuno-PET over the past few years has led to the growth in clinically used positron-emitting radionuclides [1]. In particular Gallium (⁶⁸Ge/⁶⁸Ga) generators are becoming ever more prevalent in PET/CT facilities for gallium-labelled imaging of prostate cancer and neuroendocrine tumours [2, 3], while other radioisotopes such as ¹¹C, ¹³N, ¹⁵O, ⁶⁴Cu, ⁸⁹Zr and ⁸²Rb have also demonstrated their potential for more widespread clinical use [1]. The decay schemes of each of these radioisotopes are markedly different from ¹⁸F, with different endpoint energy for the emitted positrons and, in some cases, additional high energy gamma radiation [4, 5] (table 1). This has implications for the occupational exposure of nuclear medicine personnel involved in the manipulation and dispensing of radiopharmaceuticals [6].

Occupational doses in the form of skin dose (Hp(0.07)) and deep dose (Hp(10)) are typically monitored for PET and nuclear medicine personnel [7]. In order to reduce occupational exposure, the use of commercially available syringe shields is recommended [8]. These shields, originally designed to attenuate the 511 keV gamma photons of ¹⁸F, are now routinely used with a range of other PET radionuclides despite the fact that, in general, these nuclides have more complex decay schemes than the pure positron (β⁺) emitting ¹⁸F. Indeed, the emission of higher energy positrons, γ-gamma rays and beta (β⁻) particles can all have significant implications for occupational exposure. Thus, careful consideration must be paid to use of shielding designed specifically for ¹⁸F when dealing with other PET radionuclides.

Calculations based on the decay characteristics of ⁶⁸Ga and ¹⁸F had found that the skin dose rate (mSv/MBq.hr) due to direct contact with an unshielded 5 ml syringe is approximately 11 times higher for ⁶⁸Ga than ¹⁸F [6, 9]. The positrons from ¹⁸F have a lower energy and range than those of ⁶⁸Ga and, thus, many of the ¹⁸F positrons do not contribute to skin dose, as they are stopped by the wall of the syringe. The contact skin dose rates for ¹¹C, ¹³N and ¹⁵O have been reported to be approximately 2, 4 and 11 times higher than that of ¹⁸F, respectively [9]. ⁶⁴Cu, with its lower positron energies and less frequent emissions, has a contact dose rate approximately equal to 20% of that of ¹⁸F. The above calculations, however, are based on simple and limited geometries, which may not reflect the actual dose rates received in clinical practice.

The International Commission on Radiation Protection (ICRP) guidelines on eye lens dose monitoring [10] state that monitoring of the beta radiation dose contribution to the eye lens (Hp(3)) for isotopes with maximum energies >700 keV may be required if the shielding used is not sufficient to absorb the beta radiation completely. Beta particles with maximum energies in excess of 700 keV can penetrate the lens of the eye resulting in an exposure. While eye dose monitoring is not routinely performed in PET departments where ¹⁸F is the only radionuclide employed, for higher energy positron-emitting radionuclides there is the potential for increased eye doses, particularly in situations where staff are exposed to unshielded sources, so eye dose monitoring may be required.

The literature has reported Monte Carlo simulations of skin dose rates (Hp(0.07)) and deep dose rates (Hp(10)) for various situations where an operator is in direct contact or distant from some unshielded PET radionuclide sources [11, 12]. However, to date, skin, eye and deep doses from shielded PET radionuclide syringe sources have not yet been described. Accordingly, the aim of this study was to address some of these gaps by establishing, through Monte Carlo simulation and experimental measurement, Hp(0.07), Hp(10) and Hp(3) doses received from shielded and unshielded syringes containing a range of PET radionuclides. As this study specifically assesses the radiation exposure from positron-emitting radionuclide solutions in syringes, the results are primarily relevant during dispensing and administration tasks.

A number of different Monte Carlo codes have been employed for radiation transport applications, including GEANT4, MCNP5, Penelope and EGNnrc. In this work, Monte Carlo simulations were carried out with EGSnrc version v2019a, National Research Council Canada [13]. EGSnrc is a software toolkit that performs Monte Carlo simulation of ionising radiation transport through matter. It models the propagation of photons, electrons and positrons with a range of kinetic energies in homogeneous materials. EGSnrc is widely used in medical physics applications, including modelling of photon and electron beams in linear accelerators, dose determination, detector response characterisation and assessment of radiation shielding.

The sources were simulated using the EGSnrc radionuclide source module according to their evaluated nuclear structure data file [14]. Electrons and photons were followed down to a kinetic energy of 10 keV. All results were normalised to a time-integrated activity of 1 MBq.hr. The number of histories used in each simulation was chosen to ensure relative statistical uncertainties lower than 3% (comparable to typical uncertainties in radionuclide activity measurements and significantly lower than the tolerances of most commonly used survey meters), unless otherwise noted.

2.1. Validation of EGSnrc

In order to first validate the suitability of EGSnrc and its radionuclide source module for dose evaluations Monte Carlo simulations of radioactive aqueous solutions using the GEANT-4 code [15], as described in Amato et al [11] were reproduced making use of EGSnrc. Comparison of the results not only provided confirmation of the suitability of EGSnrc for this type of simulation, but also allowed a comparison to be made between two different radiation transport algorithms. The modelled geometry consisted of a radioactive water solution contained within a cylindrical receptacle of internal diameter of 1 cm and volume of 2.5 cm³. The cylindrical source was then placed at the centre of a spherical shell of soft tissue (figure 1(a)). The soft tissue was considered to be composed of ICRP 4 component soft tissue (ρ = 1.03 g cm⁻³; 10.12% H, 11.1% C, 2.6% N and 76.18% O—percentages per weight) [16]. The soft tissue shell was 10 cm thick and had an inner radius varying from 10 to 100 cm, in order to evaluate doses at 10, 30, 50 and 100 cm distance from the source. Two scoring volumes were defined inside the absorber. A spherical shell of 10 µm thickness was centred at a depth of 70 µm (65–75 µm) to evaluate Hp(0.07). A 2nd spherical shell of 1 mm thickness was centred at a depth of 10 mm (9.5–10.5 mm) to evaluate Hp(10). Dry air (ρ = 1.20479 × 10⁻³ g cm⁻³) filled the space between the cylindrical source and the spherical shells. The average per cent deviation of EGSnrc from Amato's work was found to be −0.2% and 0.8% (all isotopes <±3%) for the Hp(10) deep dose at 10 cm and 30 cm, respectively, from the radionuclide source. In the case of the Hp(0.07) skin doses, the average per cent deviation of EGSnrc with respect to Amato was −6.9% and −5.2% at 10 cm and 30 cm, respectively, from the radionuclide source. The per cent deviation ranged from 0.8% for ¹⁸F to a maximum of −11.6% for a ⁶⁸Ga radionuclide source. Uncertainties of this magnitude are well below the accepted uncertainties of commonly used survey meters in PET departments, which are of the order of ±30%.

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As a further validation of EGSnrc, we reproduced the geometries used by Italiano et al [12] for modelling the fingers of an operator in direct contact with a receptacle containing ¹⁸F. The GEANT-4 simulations by Italiano [12] considered a cylindrical syringe composed of polyethylene (σ = 0.94 g cm⁻³), with wall thickness of 1 mm, inner diameter of 1.0 cm and length of 4 cm. ¹⁸F was homogeneously distributed in a water solution, which filled the syringe volume up to a length of 2 cm and the remainder of the syringe contained air. Italiano et al [12] simulated three different finger locations in contact with the syringe wall (figure 1(b)). The fingers were represented as three individual annuli of soft tissue (ICRP4 component soft tissue σ = 1.0 g cm⁻³), with 1 cm thickness. Hp(0.07) was scored at a depth of 65–75 µm. All geometries were reproduced in EGSnrc, although there was a small difference in the density of polyethylene used (0.93 g cm⁻³ in EGSnrc compared to σ = 0.94 g cm⁻³ in GEANT4). The modelled doses using EGSnrc were within −6% and 2% of those reported using GEANT-4 for each simulated finger position for ¹⁸F.

2.1.1. Syringe source model.

After the validation procedure was completed, the syringe model was optimised to more accurately reflect the actual syringe used in our institution, namely the BD Plastipak 5 ml syringe [17]. This cylindrical syringe has a uniform polypropylene (ρ = 0.9 g cm⁻³) wall of 0.091 cm thickness and an internal diameter of 1.18 cm (figure 2(a)). In our model, the needle end of the syringe replicated the Luer-Lok. The radioactive water solution was contained within the 1st 2–2.2 ml of the syringe followed by a 0.5 cm thick cylindrical disc of polypropylene, representing the cap of the plunger. The remainder of the hollow syringe was filled with dry air. The plunger handle and needle were not included in this model.

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2.1.2. Syringe shield model.

The details of a selection of commercially available PET syringe shields modelled in this study are summarized in table 2.

Table 2. Commercially available syringe shields assessed in this study.

Manufacturer	Model	Thickness (mm)	Composition	Density (g cm−3)	Attenuation of 511 keV
Britec	PET syringe shield	7.5 [18]	90% tungsten, nickle and copper mixed.	18.3*	Not specified
Biodex	Pro-tec syringe shield	9 [19, 20]	Tungsten	19.3	88%
Biodex	Z-PET	14 [21]	Tungsten	19.3	97%
Britec	Lead glass	11–13 [18]	4 mm lead equivalent	11.4	Not specified

Note:^*The density of the 7.5 mm Britec shield syringe was calculated by assuming a composition of 90% W, 5% Cu and 5% Ni.

The thickness and composition of the shield for each simulation was modified to reflect the actual shield being assessed. While EGSnrc contained tungsten and lead density correction files, it was necessary to create a unique density correction file for the Britec tungsten composite 7.5 mm syringe shield using energy response data from NIST [22].

2.1.3. Soft tissue model.

The spherical soft tissue phantom employed by Amato et al [11] simulates the average exposure at any orientation at the defined distance from the syringe; this is a reasonable approach for uniform isotropic sources. However, in practice the syringe is not shielded entirely as the syringe is tubular and is open at both ends. When the tubular syringe shield is in place positrons and photons emitted from the unshielded ends of the syringe can also contribute to exposure. In order to exclude the direct irradiation from the unshielded portion of the syringe the spherical phantom was clipped by two bounding planes, optimally positioned for each source to detector distance. The dose rates simulated using this model provide a reasonable estimation of the average dose a person would receive at a distance from the shielded barrel of the syringe. However, a higher dose would be received if a person was positioned directly in front of or behind the shielded syringe. In that situation the dose would be significantly higher. A further modification was made to the soft tissue shell to replace the 1st 2 mm of layer of soft tissue with 2 mm skin (ICRP skin σ = 1.1 g cm⁻³) for assessment of Hp(0.07) and Hp(10) (figure 2(b)). For simulation of Hp(3) the spherical shell was composed entirely of ICRP4 component soft tissue with no skin layer. The eye dose scoring volume was defined as a spherical shell at the tissue equivalent depth of the sensitive volume of the eye lens, between 2.80 mm and 3.82 mm contained inside the absorber [23].

2.1.4. Contact dose model.

The contact finger dose model implemented in this study was based on the model by Italiano et al [12]. Three different finger locations were simulated in contact with the syringe wall. The finger model employed in this study consisted of 2 mm skin in contact with the syringe, followed by 1.8 cm of soft tissue (ICRP4 component soft tissue σ = 1.0 g cm⁻³) for a total thickness of 2 cm and a width of 2 cm. Hp(0.07) was scored at a depth of 65–75 µm. The contact dose model employed in our study considered only one finger (F1) to have direct contact with the portion of the syringe containing the radioactive solution (figure 2(c)). This position corresponds to the maximum dose equivalent to which an operator can be exposed to when manipulating the syringe. The remaining two fingers (F2 and F3; figure 2(c)) were positioned over the air-filled section of the syringe. The syringe modelled for contact dose was considered to have a total length of approximately 6.7 cm to accommodate the three finger positions and the radioisotope was homogeneously distributed in a water solution up to a height of 2 cm (volume 2.2 ml). A cross section of the syringe simulation models used in this study are illustrated in figure 2.

2.2. Experimental validation of modelled doses

EGSnrc simulation results for dose rates at a distance of 30 cm from the unshielded and shielded syringes are presented here. The results for distances of 10 cm and 50 cm from the syringe are presented in tables S1 and S2, respectively in the supplementary data section (available online at stacks.iop.org/JRP/41/1060/mmedia). As ⁸²Rb is prepared and dispensed through an automated infusion system, it is very unlikely to be stored or manipulated in a syringe. However, once this dispensing is complete, it is often administered to the patient through an unshielded administration line. The dose rates for ⁸²Rb in an unshielded syringe, while not directly clinically relevant, are presented here to illustrate the potential risk of occupational exposure from unshielded sources of ⁸²Rb. The results of EGSnrc simulations for Hp(0.07), Hp(3) and Hp(10) at a distance of 30 cm from the unshielded and shielded syringe are shown in table 4, and the skin dose rates Hp(0.07) for each shield are illustrated in figures 3 and 4, respectively.

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The results of EGSnrc simulations for contact skin exposure rates from the unshielded syringe are shown in table 5. The results of the shielded syringe simulations are illustrated in figure 5 and the corresponding data are provided in table S3 in the supplementary data section.

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Table 6 displays the conversion factors to estimate Hp(0.07) from Hp(10) and Hp(3) from Hp(10) at 30 cm from the syringe, for each isotope.

The conversion factors to estimate Hp(3) from Hp(10) were found to be between 1.0 and 1.3 for all geometries for ⁶⁴Cu, ¹⁸F, ¹¹C, ¹³N and ⁸⁹Zr. It is, thus, reasonable to estimate the eye dose as being approximately equal to the deep dose for these isotopes, for all geometries. For ¹⁵O, ⁶⁸Ga and ⁸²Rb in the case of the unshielded syringe, the deep dose to eye dose conversion factors were found to be approximately 1.6, 2.1 and 9.2, respectively. These conversion factors reduce to between 1.1 and 1.2 and 1.2 and 1.4 for ¹⁵O and ⁶⁸Ga, respectively, when any of the syringe shield assessed in this study are in place. These conversion factors can be used to estimate the skin and eye dose rates in situations where the deep dose rate can be measured in real time or is known.

Manipulation of unsealed positron-emitting radionuclides can result in significant skin doses to the hands of staff during preparation (labelling/dispensing) and administration of the PET radiopharmaceuticals. The occupational exposure will depend not only on the activity of the radionuclide but also on the radiation protection measures employed (time, distance, and shielding). PET centres that have exclusively used ¹⁸F should be aware of the potential for much higher occupational extremity exposure with the introduction of higher energy positron emitting nuclides, with dose rates from unshielded sources significantly higher than that of ¹⁸F. The contact skin dose rate for an unshielded syringe containing ⁶⁸Ga was found to be 11 times higher than that for ¹⁸F, when the syringe is held close to the active volume (finger position F1). This is in excellent agreement with previously published values [6]. Based on the simulation results for F1 obtained in this study, the time taken to reach the annual dose limit of 500 mSv for an operator holding an unshielded syringe of 200 MBq would be approximately 205, 48, 18, 10, 5, 4, 33 and 2 min for ⁶⁴Cu,¹⁸F, ¹¹C, ¹³N, ¹⁵O, ⁶⁸Ga, ⁸⁹Zr and ⁸²Rb, respectively. Thus, care must be taken to avoid direct or indirect exposure to unshielded radionuclide sources; syringe shields and forceps should be used where possible when handling unsealed radioactive sources.

As most commercially available PET syringe shields have a thickness of the order of 7–14 mm of tungsten, they should effectively absorb the positrons from all isotopes assessed in this study and significantly attenuate the gamma radiation. The addition of a syringe shield achieves a significant reduction in the contact skin dose for all isotopes. The 7.5 mm W/Ni/Cu shield achieved a reduction in Hp(0.07) of 96.7% ± 2.7% at finger position F1. The percentage reduction at position F1 for the 9 mm W shield was 98.3% ± 1.8%, and 99.4% ± 0.7% for the 14 mm W shield. The 4 mm lead equivalent shield, simulating the lead glass portion of the shield, achieved a reduction of rate of 91.9% ± 7.7%. The contact skin dose rate for ⁶⁴Cu is significantly lower than that of the other isotopes; for all shields, it is approximately 20% of the contact skin dose rate of ¹⁸F. With the exception of the lead glass shield, the contact skin dose rate for ⁸⁹Zr is notably higher than that of the other isotopes; it is approximately 1.4, 1.7 and 3.1 times the contact skin dose rate of ¹⁸F, for the 7.5 mm, 9 mm and 14 mm shield, respectively. The contact skin dose rate is approximately equal for all other isotopes for each shield type, as there is very little contribution in this geometry to the finger dose from the positrons at the unshielded ends of the syringe shield. In all cases the contact doses rates at positions F2 and F3 are significantly lower than that of F1. If the syringe must be handled directly, the operator should ensure that their fingers are not in contact with the shield at a position directly over the radionuclide source and should also avoid directly handling the lead glass viewing window portion of the syringe.

The syringe shields are specified by their attenuation of the 511 keV annihilation photons, which should correspond to the specified reduction in deep dose. For the realistic tubular syringe model simulated in this study, the attenuation of photons at a distance of 30 cm from the source, as measured by Hp(10), was found to be of the order of 73%, 80%, 87% and 47% for the 7.5 mm, 9 mm, 14 mm and 4 mm shields, respectively, for all isotopes excluding ⁸⁹Zr. The specification is most likely based on the attenuation offered by the composition of the syringe material in a simple geometry. It does not take into account the high energy positrons and gamma photons escaping from the unshielded portion of the syringe, which contribute to an increase in Hp(0.07), Hp(3) and Hp(10) at a distance from the syringe. This effect is not evident when the operator's hands are in direct contact with the syringe.

The abundant presence of the highly penetrating 909 keV photons of ⁸⁹Zr results in less effective attenuation for the shields assessed in this study for this isotope. The attenuation of ⁸⁹Zr photons at a distance of 30 cm from the source, as measured by Hp(10), was found to be of the order of 55%, 63%, 75% and 29% for the 7.5 mm, 9 mm, 14 mm and 4 mm shields, respectively. This is notably less than for the other isotopes assessed in this study. While Hp(10) at a distance of 30 cm from the unshielded syringe containing ⁸⁹Zr is approximately the same as that of ¹⁸F, when any of the shields assessed in this study are in place, Hp(10) for ⁸⁹Zr is approximately twice that of ¹⁸F. Alzimami et al [26] compared the occupational exposure to staff as a result of emissions from patient administrations of ¹⁸F and ⁸⁹Zr. They found that, in close proximity to the patient source, the dose rates where similar for both isotopes (within 20%). However, when the dose rate was measured outside the room, the dose rate from ⁸⁹Zr was up to 22 times higher than that of ¹⁸F, owing to the reduced attenuation of the high energy 909 keV ⁸⁹Zr photon by the structural shielding. Holland et al [27] observed that cyclotron operators and radiochemists working in facilities originally designed for ¹⁸F experience large increases in occupational doses when handling ⁸⁹Zr. The results obtained here further confirm that special consideration should be given to radiation protection of staff when ⁸⁹Zr is used in the department. ⁸⁹Zr will require additional shielding for transport and safe handling than is generally considered adequate for pure positron emitters such as ¹⁸F.

For the remaining isotopes in this study, when any of the syringe shields are in place, Hp(10) simulated values at a distance of 30 cm from the shielded syringe, are comparable to ¹⁸F for all isotopes (within 14%); with the exception of ⁶⁴Cu whose deep dose rate is only 20% of ¹⁸F. However, the Hp(0.07) estimate is in some cases, significantly higher than ¹⁸F for the isotopes studied, again with the exception of ⁶⁴Cu.

Eye doses are not usually of concern for isotopes with a maximum positron energy below 700 keV [23], such as ¹⁸F and ⁶⁴Cu. However, for the other PET isotopes considered in this study there is the potential for an increased eye dose, particularly in situations where the radionuclide source is not shielded. While the eye dose model presented here is a simplified model based on the tissue equivalent depth of the eye, it provides a useful estimation of the eye dose. Simulations in this study suggest that Hp(3) at a distance of 50 cm from an unshielded syringe are comparable to ¹⁸F for ¹¹C, ¹³N and ⁸⁹Zr (within 30%). In contrast, the eye doses for ¹⁵O, ⁶⁸Ga, and ⁸²Rb were found to be 1.6, 2 and 14 times that of ¹⁸F, respectively. Taking these Hp(3) estimations at 50 cm from an unshielded source of 200 MBq, the time taken to reach the annual limit of 20 mSv would be approximately 88 h, 73 h and 10 h for ¹⁵O, ⁶⁸Ga and ⁸²Rb, respectively. Eye dose monitoring may be required if high activities of unshielded sources of ⁶⁸Ga, ¹⁵O or ⁸²Rb are in use in the department. In the case of patient administration through an unshielded line, the distance between the line and the operator, shielding between the line and the operator, the workload and the infusion duration should also be taken into account.

When any of the syringe shields assessed in this study are in place, Hp(3) is comparable to that of ¹⁸F for all isotopes, with the exception of ⁸⁹Zr. Due to the presence of the highly penetrating 909 keV gamma photon, Hp(3) for ⁸⁹Zr is approximately twice that of ¹⁸F when a syringe shield is in place. ⁸²Rb in a shielded syringe was not assessed as this case is not clinically relevant due to the automatic infusion method typically employed for ⁸²Rb radiopharmaceuticals.

The results presented in this paper, both for the shielded and unshielded syringe, will apply whenever the operator is holding a 5 ml syringe or positioned at a distance from a 5 ml syringe. The syringe geometries and configurations simulated in this study are mostly relevant to dispensing and administration tasks performed by the operator. The preparation and QC tasks for some of the more novel radionuclides may require more complex manipulations in geometries not covered by the simulations in this study. Radionuclides with higher energy positrons and additional gamma photons compared to ¹⁸F, will also result in increased transmission rates if the radionuclide is in a smaller geometry syringe, for example in a 1 ml syringe for pre-administration QC, or other clinically relevant plastic configurations such as IV tubing.

The results of the simulations provided in this study can assist in the selection of the optimum syringe shield, although consideration is also needed for the workload and the associated administered activity of each isotope. Although the dose rates are higher for ⁶⁸Ga than ¹⁸F, the administered activity and number of patients per week is generally much less for ⁶⁸Ga than ¹⁸F. In our centre, the administered activity for ⁶⁸Ga is 100–130 MBq, whereas the administered activity for ¹⁸F FDG is weight-based—3 MBq kg⁻¹ up to a maximum of 300 MBq. Ease of use and weight should also be considered when selecting the appropriate syringe. As expected, the 14 mm tungsten shield provides the highest protection from the shields assessed in this study. However, as the thickness of the syringe shield increases, the weight also increases which can make the shield more challenging to use. The shields assessed in this study accommodate a 5 ml syringe. For this syringe size, the weight of the 14 mm shield is 1.7 kg compared to 0.77 kg for the 9 mm shield and 0.6 kg for the 7.5 mm shield. Another consideration is the degree of manipulation that is required by the operator. The heavier shields generally do not contain a lead glass viewing window. The presence of the viewing window can reduce the overall time the operator spends manipulating the source and can be useful when removing air-bubbles and confirming volumes. The dose rates from the lead glass viewing window are significantly higher than from the tungsten barrel of the syringe, so care must be taken to avoid direct contact with this portion of the shield. The attenuation provided by the shields assessed in this study may not be sufficient for use with ⁸⁹Zr in the case of high activities being handled or high patient numbers. Special consideration should be given to the shielding used for the manipulation, storage, transport and administration of ⁸⁹Zr, including the use of an automated delivery system.

Our study has shown that it is possible to make realistic estimates of Hp(10), Hp(0.07) and Hp(3) for a range of PET radionuclides and syringe shields using Monte Carlo simulation. The results of these simulations can be used to estimate conversion factors to determine Hp(0.07) and Hp(3) doses using real-time measurements of Hp(10). For the isotopes analysed in this study, with the exception of ⁶⁴Cu, the positrons have a higher energy and range than those of ¹⁸F and can potentially result in significant skin dose for unshielded sources. Procedures which involve exposure to unshielded sources of high energy positron emitting isotopes should be assessed to ensure all appropriate radiation safety measures are employed to reduce staff doses. The appropriate shield for use with each isotope will depend on its ease of use and the range of isotopes and activities that will be handled. Special consideration should be given to the selection of appropriate shielding for ⁸⁹Zr. Eye dose monitoring may be required if high activities of unshielded sources of ⁶⁸Ga, ¹⁵O or ⁸²Rb are in use in the department.

This work was funded by a Government of Ireland Postgraduate Scholarship from the Irish Research Council (GOIPG/2019/3652).