How much do 68Ga-, 177Lu- and 131I-based radiopharmaceuticals contribute to the global radiation exposure of nuclear medicine staff?

New occupational dosimetry data

In total, 69 completed data sets from 6 hospitals have been collected for 177Lu, 65 completed data sets from 6 hospitals for 68Ga and 13 completed data sets from 2 hospitals for 131I. In Table 3, the Hp(10), Hp(3) and Hp(0.07) doses are reported for the 3 isotopes, averaged over all participants. All dose data are normalized to the total isotope-specific activity manipulated (Atot) while wearing the dosemeter sets.

Table 3 Average whole-body dose Hp(10), average maximum eye lens dose Hp(3) and average maximum extremity dose Hp(0.07), normalized to manipulated activity [µSv/GBq] for all 3 isotopesWhole-body and eye lens dosimetry

From Table 3, it can be observed that highest whole-body doses are observed for 68Ga. In general, many whole-body dosemeter sets resulted in measurement values below the DL: 108 out of 148, i.e. 73%. In Fig. 2, the variation in Hp(10) for the different hospitals and for each isotope is demonstrated. For the eye lens doses, again 73% of measurements resulted in values below the DL for left and right eye together. When dose measurements exceeded the DL for at least one eye, it was impossible to determine which side typically had the highest dose. Consequently, the analysis considered the maximum eye lens dose measured without distinguishing between the left or right eye as a conservative estimation. The highest doses are again observed for 68Ga.

Fig. 2figure 2

Variation in Hp(10) per normalized activity at each hospital for 177Lu (a), 68Ga (b) and 131I (c). Boxplots with minimum and maximum, 1st and 3rd quartile, median and average (x) values and outliers (dots)

Extremity dosimetry

In Table 3, also the average maximum Hp(0.07) extremity doses are reported for the 3 isotopes, normalized to the total activity handled and averaged over the different participants and tasks performed, with highest doses determined once more for 68Ga. A more extensive evaluation is performed separately for 68Ga and 177Lu below. For 131I, only 13 datasets have been evaluated, so it is not included in the detailed analysis.

68Gallium

In Table 4, the average maximum extremity doses, normalized to the manipulated activity, are compared across different hospitals for three distinct tasks: preparation + dispensing, administration and QC. Data sets that involve a combination of activities (such as preparation + dispensing + QC, preparation + dispensing + administration, preparation + dispensing + QC + administration, or dispensing + administration) are excluded from this comparison due to the difficulty in making accurate comparisons. The lower dose values observed at Hospital D for preparation and dispensing can be attributed to their fully automatic elution, preparation, and dispensing procedures. In contrast, other hospitals use an automated system for elution and preparation, but the dispensing is done manually, and shielding is applied to the syringes only after measuring the activity in a radioactivity meter. The administration of 68Ga is always performed manually with shielded syringes. Consequently, the observed variations in extremity doses during administration can be explained by individual differences in how each technologist handles the syringe. All hospitals use Pb shielding for the vial while preparing or dispensing the 68Ga and W shielding for the syringes during dispensing and administration.

Table 4 Maximum extremity dose, per manipulated activity, [mSv/GBq] in the different hospitals for preparation + dispensing of the 68Ga vial, for administration of the 68Ga syringes and for QC tests

For general QC procedures, a small amount of activity (a few µL; 20–100 kBq per QC procedure) is used for various QC tests, such as thin layer chromatography (TLC), pH and half-life analyses. The total activities handled, involving multiple QC procedures over several days, ranged between 60 and 600 MBq. These tests are conducted quickly, but without any shielding. This resulted in extremity dose measurements well above the DL of 50 µSv, with maximum extremity doses per data set ranging between 2.3 and 23 mSv. This explains why the normalized maximum dose values per manipulated activity are much higher compared to other tasks, as the manipulated activities for QC procedures are much smaller.

177Lutetium

In Table 5, the average maximum extremity doses, normalized to the manipulated activity, are compared among various hospitals for two specific tasks: preparation + dispensing and dispensing + administration. The elevated extremity doses observed in hospital K can be attributed to the manual preparation and dispensing processes, in contrast to hospital I, where these tasks are fully automated. In hospitals D, E and J, the preparation phase is automated, while the dispensing of syringes is done manually for D and E, and in hospital J it is automated for single patient synthesis and manual for two patients per synthesis. Across all hospitals, the administration of 177Lu is done using either semi-automatic or fully automatic systems, including injection systems, infusion pumps or infusion methods. The dose values from hospital D involve both dispensing and administration, while in the other centers only administration is performed in the data sets included in Table 5. Shielding is used in every hospital: usually Pb and PMMA for vial shielding and W or Pb for syringe shielding.

Table 5 Maximum extremity dose, per manipulated activity, [µSv/GBq] in the different hospitals for preparation + dispensing of the 177Lu vial and for administration of the 177Lu syringesRatio of maximum dose to ring dose

Approximately 75% of maximum extremity doses for 68Ga are measured on the fingertips of the thumb, index or middle finger of the non-dominant hand, while 25% are on the thumb or index finger of the dominant hand. For 177Lu, maximum dose positions are more equally distributed between both hands’ fingertips. It should be noticed that for 177Lu, the variation in measured dose ranges across both hands is rather small. In many cases, if the maximum dose was observed on the dominant hand, the dose values on the non-dominant hand were in the same range as well. The average ratio between the maximum dose and the dose at the base of the middle finger (possible routine ring dosemeter position) is around 5 for both68Ga and 177Lu (Fig. 3), and therefore consistent with current recommendations to apply a correction factor [10].

Fig. 3figure 3

Ratio between maximum dose and dose measured at the base of the middle finger for 68Ga and 177Lu

Contribution to the total occupational extremity doses

The cumulative extremity dose values measured at the base of the middle finger of the non-dominant hand for 68Ga and 177Lu during this study were compared to routine monthly ring dosemeter values for the same periods. As an example, Fig. 4 shows cumulative doses for participant D4, comparing routine ring doses and 68Ga-specific doses, monitored during 68Ga administration. The green bars represent the monitoring periods in the study and the total dose at the base of the middle finger of the non-dominant hand of each such period has been shown in a cumulative way. Similarly, the routine monthly ring doses are summed within each monitoring period and also shown in Fig. 4 in a cumulative way. The routine ring doses for months when no study-dosemeter sets have been used (for example D4, this is oct–dec 2022), are omitted. The ratio of the slopes of the cumulative ring dose curves indicates that 26% of the total routine dose comes from the administration of 68Ga. Next, the workload of each participant was assessed in terms of total activity for each handled isotope. For some centers, detailed personal monthly data for each isotope were available, while others provided typical yearly workloads (e.g., number of patients x activity per syringe) and the total number of staff handling the isotopes. For participant D4, 2% of the yearly activity involved 68Ga, 80% involved 99mTc, 17% involved 18F and 0.7% involved 123I. Since 26% of D4’s total routine finger dose came from 68Ga-injections, despite only 2% of the handled activity being 68Ga, it was concluded that 68Ga administration results in 13 times more extremity dose compared to the manipulated activity from other isotopes. Tables 6, 7, 8 and 9 summarize this analysis for all NM staff (with minimum 2 dosemeter sets per isotope) involved in 68Ga administrations, 68Ga synthesis, 177Lu administrations and 177Lu preparations, respectively.

Fig. 4figure 4

Monthly cumulative routine ring doses and 68Ga-specific fingerdose data for the monitoring periods (green bars) of participant D4

Table 6 Contribution of the 68Ga finger dose compared to the total finger dose from all isotopes for participants administering 68GaTable 7 Contribution of the 68Ga finger dose compared to the total finger dose from all isotopes for participants synthesizing68GaTable 8 Contribution of the 177Lu finger dose compared to the total finger dose from all isotopes for participants administering 177LuTable 9 Contribution of the 177Lu finger dose compared to the total finger dose from all isotopes for participants preparing177LuExtrapolation to annual doses

Tables 10, 11, 12, and 13 show the extrapolated yearly doses for NM staff, including whole-body dose [Hp(10)], maximum eye lens dose [Hp(3)] and maximum extremity dose [Hp(0.07)], for the synthesis or administration of 68Ga and 177Lu radiopharmaceuticals separately. These values can be compared against the annual occupational dose limits: 20 mSv/year for Hp(10) and Hp(3) and 500 mSv/year for Hp(0.07) [20].

Table 10 Extrapolated annual doses (Hp(10), Hp(3), Hp(0.07)) for NM staff performing 68Ga administrationsTable 11 Extrapolated annual doses (Hp(10), Hp(3), Hp(0.07)) for NM staff performing 68Ga synthesisTable 12 Extrapolated annual doses (Hp(10), Hp(3), Hp(0.07)) for NM staff performing 177Lu administrationsTable 13 Extrapolated annual doses (Hp(10), Hp(3), Hp(0.07)) for NM staff performing 177Lu synthesis

For 177Lu, annual doses are below 0.5 mSv for both whole-body and eye lens doses during radiopharmaceutical synthesis and administration. Yearly maximum extremity doses stay below 100 mSv for synthesis and only several mSv for administration. For 68Ga, annual Hp(10) can reach nearly 3 mSv, and Hp(3) can reach 5–6 mSv. For participant G5, who only performs QC of 68Ga pharmaceuticals, an annual eye lens dose of 12 mSv is estimated. Yearly extremity doses stay below 100 mSv for 68Ga administration but can reach up to 600 mSv for synthesis and dispensing.

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