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

Abstract

Background

The radiation exposure of nuclear medicine personnel, especially concerning extremity doses, has been a significant focus over the past two decades. This study addresses the evolving practice of NM, particularly with the rise of radionuclide therapy and theranostic procedures, which involve a variety of radionuclides such as ⁶⁸Ga, ¹⁷⁷Lu, and ¹³¹I. Traditional studies have concentrated on common radioisotopes like ^99mTc, ¹⁸F, and ⁹⁰Y, but there is limited data on these radionuclides, which are more and more frequently used. This study, part of the European SINFONIA project, aims to fill this gap by providing new dosimetry data through a multicenter approach. The research monitors extremity doses to hands, eye lens doses, and whole-body doses in nuclear medicine staff handling ⁶⁸Ga, ¹⁷⁷Lu, and ¹³¹I. It examines the type of activities performed and the protective measures used. The study extrapolates measured doses to annual doses, comparing them with annual dose limits, and assesses the contribution of these specific procedures to the overall occupational dose of nuclear medicine personnel.

Results

Measurements were conducted from November 2020 to August 2023 across nine hospitals. The highest whole-body, eye lens and extremity doses were observed for ⁶⁸Ga. Average maximum extremity doses, normalized per manipulated activity, were found of 6200 µSv/GBq, 30 µSv/GBq and 260 µSV/GBq for ⁶⁸Ga, ¹⁷⁷Lu and ¹³¹I, respectively. Average whole-body doses stayed below 60 µSv/GBq for all 3 isotopes and below 200 µSv/GBq for the eye lens dose. The variation in doses also depends on the task performed. For ⁶⁸Ga there is a risk of reaching the annual dose limit for skin dose during synthesis and dispensing.

Conclusions

This study’s measurement campaigns across various European countries have provided new and extensive occupational dosimetry data for nuclear medicine staff handling ⁶⁸Ga, ¹⁷⁷Lu and ¹³¹I radiopharmaceuticals. The results indicate that ⁶⁸Ga contributes significantly to the global occupational dose, despite its relatively low usage compared to other isotopes. Staff working in radiopharmacy hot labs, labeling and dispensing ¹⁷⁷Lu contribute less to the finger dose compared to other isotopes.

Background

The radiation exposure of nuclear medicine (NM) personnel has received quite some attention over the last two decades by carefully monitoring extremity doses for the most common radioisotopes, such as ^99mTc, ¹⁸F and ⁹⁰Y, showing that there is a real risk to exceed the annual dose limit to the skin, especially at the fingertips [1–8]. As a result, wearing a ring dosemeter, in addition to the whole-body dosemeter, became more and more normal practice for NM staff and reports have been published with recommended correction factors to assess the maximum skin dose on the hand, based on the dose measured by the ring dosemeter [9–11].

However, NM practice has evolved strongly during the last years with the upcoming radionuclide therapy and theranostic procedures. This resulted in a larger variety of radionuclides that are handled, higher activities manipulated for the therapeutic procedures and exposure to a greater variety of radiation types (gamma, beta, positrons, …). In the international literature, small-scale studies can be found for these new emerging radioisotopes within the theranostic isotope family, such as ⁶⁸Ga [12, 13] and ¹⁷⁷Lu [2, 14–17], but they are scarce and with varying study design and set-up. A recent review paper has also been published on extremity dosimetry for NM staff for emerging isotopes, where only 5 papers (published after 2000] were found for ¹⁷⁷Lu, 2 papers for ⁶⁸Ga and additionally for the more long-used isotope, ¹³¹I, only 8 papers were found [18].

Therefore, as part of the European SINFONIA project, this study aims to provide new dosimetry data by a multicenter approach for NM staff, specifically working with ⁶⁸Ga, ¹⁷⁷Lu and/or ¹³¹I. Besides monitoring the extremity doses to the hands, also eye lens doses and whole-body doses have been monitored for the above-mentioned isotopes, considering the type of activity performed (preparation, dispensing or administration of radiopharmaceuticals) and type of protection used. An extrapolation of measured doses to annual doses is performed and compared with the corresponding annual dose limits. Finally, the contribution of the radiation dose from these specific procedures to the global occupational dose for NM personnel, which is measured on monthly basis with the routine dosemeters, is assessed. As such, this multicenter approach enables us to estimate the impact of ⁶⁸Ga-, ¹⁷⁷Lu- and ¹³¹I-based radiopharmaceuticals on the global exposure of NM staff.

Material and methods

Study design

We conducted a multi-center, prospective dosimetry study to assess the radiation exposure of NM staff, while handling ¹⁷⁷Lu, ⁶⁸Ga, ¹³¹I during routine activities, providing to each participant the following dosemeter set:

• Small thermoluminescent detectors (TLD) attached on gloves at 5 different locations at the level of fingertips and the base of the fingers (Fig. 1A) to monitor extremity doses in terms of the operational quantity H_p(0.07). MTS-N (Radcard, Poland) has been used for ¹⁷⁷Lu measurements, MCP-Ns (Radcard, Poland) for ⁶⁸Ga measurements and MCP-N (Radcard, Poland) for ¹³¹I measurements. The performance of a TLD depends on the type and energy of the radiation it needs to measure and the choice of TLD types in this study has been based on the study performed by Van Hoey et al. [19].

• Eye lens dosemeters (Eye-D™, Radcard, Poland) that can be attached to the head next to both eyes (on the temple) by means of a headband (Fig. 1B) to monitor eye lens doses in terms of the operational quantity H_p(3).

• A whole-body dosemeter (InLight®, Landauer) to be worn at chest height (Fig. 1C) to measure whole-body dose in terms of the operational quantities H_p(10) and H_p(0.07).

Fig. 1.

Dosemeters used for the measurement of extremity doses (a), eye lens doses (b) and whole-body dose (c)

These dosemeters had to be worn next to the routine dosemeters available to the participant. Such a separate set of dosemeters was provided to each participant, for each radionuclide under study and only to be worn when handling the specified radionuclide. The same set of dosemeters per person and per radionuclide was worn for at least one month, with extensions for low-frequency procedures such as ¹⁷⁷Lu and ¹³¹I. The goal was to monitor at least 3 procedures per dosemeter set.

For each type of dosemeters in the set, minimum two additional dosemeters were provided to the participating centers to measure background radiation, with the average background signal subtracted from the measured signal of the corresponding dosemeter type. For each of the well-characterized detector types, a detection limit (DL) of 50 µSv was defined as a representative value, for H_p(10), H_p(3) and H_p(0.07). Every background-subtracted dose measurement below this DL, is assigned a dose value of 50 µSv.

Study analysis

In addition to wearing the dosemeters, participating staff recorded procedure details on pre-prepared sheets, such as the amount of manipulated activity, a description of the tasks performed, the use and specifications of any protective equipment. This information facilitates dosimetry analysis and comparison between isotopes, tasks and centers.

The measurements spanned from November 2020 to August 2023, involving 9 hospitals (indicated with letters C to K), coming from Belgium (C, D, E, K), Switzerland (G, J), The Netherlands (I), Spain (F) and Italy (H). Six hospitals participated for ¹⁷⁷Lu, 6 hospitals for ⁶⁸Ga and 2 hospitals for ¹³¹I. Six hospitals (C, E, F, G, J, K) are university hospitals, 1 general hospital (D) and 2 national cancer centers (I, H) are included. All involved nuclear medicine departments belong to (one of) the largest departments in their city or even country. Tables 1 and 2 provide an overview of the manipulation processes, for ¹⁷⁷Lu and ⁶⁸Ga respectively, including elution/synthesis, quality control (QC), dispensing, and administration, for each participating hospital, along with the number of data sets and people involved. For ¹³¹I, only the administration of ¹³¹I pills was involved in the measurements with 5 data sets obtained from 4 people in hospital E and 8 data sets obtained from 3 people in hospital F. The radionuclide calibrators in all hospitals, used for the activity measurements, meet the criteria for QC as requested by their national authorities and comprise daily QC tests (Zero adjustments, background, bias correction, accuracy and constancy), monthly or quarterly QC tests (energy response) and yearly QC tests (mainly linearity). Most institutes work with calibration factors and isotope-specific factors, provided by the device manufacturer or by a certified body (such as centers G and J). These are defined with calibrated long-lived sources, such as Co-57, Co-60 and Cs-137. Only in hospitals D, E and K, the radionuclide calibrators are calibrated/verified, specifically with a Ga-68 and/or Lu-177 source.

Table 1.

Overview of how the different tasks were performed in participating hospitals and number of NM staff involved for ¹⁷⁷Lu procedures

Lu-177	TASK				# sets	# persons
Hospital	Synthesis	QC	Dispensing	Administration
D	Automatic	Unshielded	Manual, unshielded	Automatic	13	2
E	Automatic	(un)shielded	Manual, shielded	Automatic	14	7
F	/	/	/	Semi-automatic, shielded	15	6
I	Automatic	(un)shielded	Automatic	Automatic	18	13
J	Automatic	/	Automatic/manual	Semi-automatic, shielded	7	5
K	Manual, shielded	Unshielded	Manual, shielded	Automatic	2	1

/: This task in not performed in the respective hospital

Table 2.

Overview of how the different tasks were performed in participating hospitals and number of NM staff involved for ⁶⁸Ga procedures

Ga-68	TASK				# sets	# persons
Hospital	Elution/synthesis	QC	Dispensing	Administration
C	Automatic	Unshielded	Manual, unshielded	Manual, shielded	5	3
D	Automatic	Unshielded	Automatic	Manual, shielded	14	4
E	Automatic	(un)shielded	Manual, unshielded	Manual, shielded	4	4
F	/	/	/	Manual, shielded	16	6
G	Automatic	Unshielded	Manual, shielded	Manual, shielded	16	5
H	Automatic	Unshielded	Manual, unshielded	Manual, shielded	10	5

/: This task in not performed in the respective hospital

Routine yearly occupational dose data were collected for staff that has worn at least two dosemeter sets for the same radionuclide within the study. It was collected both for whole-body dose and ring dose and was provided on monthly basis. Moreover, the yearly workload of these staff members was evaluated in terms of isotopes handled, the amount of activity per isotope and the specific tasks performed. As such we investigated the occupational dose contribution of the isotopes under study to the global dose burden of these NM staff, including the exposure from all isotopes handled in routine practice.

Finally, for the different dose quantities, an extrapolation to the yearly occupational dose is made by multiplying for a specific participant its average measured dose per manipulated activity with the provided annual total manipulated activity for a specific isotope. For the eye lens dose and extremity dose, the average maximum dose is always considered. In this way, we evaluated whether the isotope under study provides a significant risk to reach the corresponding annual dose limit and/or if routine monitoring is recommended, if this isotope would be the only one used.

Ethical considerations

Ethical approval was obtained, where necessary, from all Committees for Medical Ethics associated with the participating hospitals. The study adhered to the guidelines for good clinical practice (ICH/GCP) and the Helsinki Declaration, ensuring the protection of human participants. Prior to participation, each participant received an information letter and provided signed informed consent. Consent included wearing dosemeters during procedures, providing procedure information, and agreeing to the collection and analysis of routine dosimetry data. Only pseudonymized data will be used for analysis, documentation, reports, or publications, ensuring confidentiality.

Results

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 H_p(10), H_p(3) and H_p(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 (A_tot) while wearing the dosemeter sets.

Table 3.

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

Isotope	Hp(10)/Atot [µSv/GBq]	Max Hp(3)/Atot [µSv/GBq]	Max Hp(0.07)/Atot [µSv/GBq]
68Ga	58	204	6200
177Lu	< 3	2.6	30
131I	8.6	8.5	260

Whole-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 H_p(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. 2.

Variation in H_p(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 H_p(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

	Max Hp(0.07)/Atot [mSv/GBq
Task	Hospital C	Hospital D	Hospital E	Hospital F	Hospital G	Hospital H
Prep + Dis	4.2	2.0	8.8	*	3.9	4.2
Admin	1.3	/	3.9	2.7	3.1	5.2
QC	/	37	/	/	45	/

/: No data sets have been recorded containing measurements for the specific task alone

*This specific task is not performed in the respective hospital

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 syringes

	Max Hp(0.07)/Atot [mSv/GBq
Task	Hospital D	Hospital E	Hospital F	Hospital I	Hospital J	Hospital K
Prep + Dis	/	0.050	*	0.011	0.008	0.045
(Dis) + Admin	0.031	0.092	0.040	0.009	0.006	/

/: No data sets have been recorded containing measurements for the specific task alone

*This specific task is not performed in the respective hospital

Ratio 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. 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. 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 ⁶⁸Ga

68Ga administrations	G4	F9	F10	F5	F8	D3	D4
68Ga finger dose/routine finger dose [%]	54	29	31	25	63	8	26
Activity 68Ga/total yearly activity [%]	1.3	0.4	0.4	0.4	0.4	0.7	2
68Ga dose fraction compared to other isotopes	40	71	78	64	155	12	13

The bold lines, represent the final data that is used for the conclusions of this analysis. The data in the lines above is the data used to obtain the data in the bold lines

Table 7.

Contribution of the ⁶⁸Ga finger dose compared to the total finger dose from all isotopes for participants synthesizing⁶⁸Ga

68Gasynthesis	G1	G2	G3	G5	D1	C1
68Ga finger dose/routine finger dose [%]	41	43	23	23	54	50
Activity 68Ga/total yearly activity [%]	1.4	13	0.8	0.4	2	2.3
68Ga dose fraction compared to other isotopes	29	3	28	53	26	22

The bold lines, represent the final data that is used for the conclusions of this analysis. The data in the lines above is the data used to obtain the data in the bold lines

Table 8.

Contribution of the ¹⁷⁷Lu finger dose compared to the total finger dose from all isotopes for participants administering ¹⁷⁷Lu

177Lu administrations	F2	F11
177Lu finger dose/routine finger dose [%]	83	24
Activity 177Lu/total yearly activity [%]	3.0	3.0
177Lu dose fraction compared to other isotopes	25	7

The bold lines, represent the final data that is used for the conclusions of this analysis. The data in the lines above is the data used to obtain the data in the bold lines

Table 9.

Contribution of the ¹⁷⁷Lu finger dose compared to the total finger dose from all isotopes for participants preparing¹⁷⁷Lu

177Lu preparations	D1	D2	I3	I5	K1
177Lu finger dose/routine finger dose [%]	25	22	10	5	99
Activity 177Lu/total yearly activity [%]	90	88	40	41	66
177Lu dose fraction compared to other isotopes	0.3	0.3	0.3	0.1	1.5

The bold lines, represent the final data that is used for the conclusions of this analysis. The data in the lines above is the data used to obtain the data in the bold lines

Extrapolation to annual doses

Tables 10, 11, 12, and 13 show the extrapolated yearly doses for NM staff, including whole-body dose [H_p(10)], maximum eye lens dose [H_p(3)] and maximum extremity dose [H_p(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 H_p(10) and H_p(3) and 500 mSv/year for H_p(0.07) [20].

Table 10.

Extrapolated annual doses (H_p(10), H_p(3), H_p(0.07)) for NM staff performing ⁶⁸Ga administrations

Participants	Annual activity (A)	< Hp(10)/A >	Annual Hp(10)	< Hp(3)/A >	Annual Hp(3)	< Hp(0.07)/A >	Annual Hp(0.07)
	[GBq]	[µSv/GBq]	[mSv]	[µSv/GBq]	[mSv]	[µSv/GBq]	[mSv]
D3	24	39	0.9	39	0.9	2239	53
D4	34	17	0.6	17	0.6	1325	45
G4	8	72	0.6	622	5.0	3178	25
F9	18	75	1.4	73	1.3	1879	35
F10	18	152	2.8	105	1.9	1782	33
F5	18	53	1.0	51	0.9	2419	45
F8	18	69	1.3	61	1.1	4215	78

Table 11.

Extrapolated annual doses (H_p(10), H_p(3), H_p(0.07)) for NM staff performing ⁶⁸Ga synthesis

Participants	Annual activity (A)	< Hp(10)/A >	Annual Hp(10)	< Hp(3)/A >	Annual Hp(3)	< Hp(0.07)/A >	Annual Hp(0.07)
	[GBq]	[µSv/GBq]	[mSv]	[µSv/GBq]	[mSv]	[µSv/GBq]	[mSv]
G1	77	13	1.0	78	6.0	5841	449
G2	156	10	1.5	19	3.0	3879	607
G3	75	6	0.5	36	2.7	1072	81
G5 (QC)	4	131	0.6	2923	12.5	44674	190
D1	111	6	0.7	6	0.7	1411	156
C1	44	13	0.6	13	0.6	6922	306

Table 12.

Extrapolated annual doses (H_p(10), H_p(3), H_p(0.07)) for NM staff performing ¹⁷⁷Lu administrations

Participants	Annual activity (A)	< Hp(10)/A >	Annual Hp(10)	< Hp(3)/A >	Annual Hp(3)	< Hp(0.07)/A >	Annual Hp(0.07)
	[GBq]	[µSv/GBq]	[mSv]	[µSv/GBq]	[mSv]	[µSv/GBq]	[mSv]
F2	155	1.6	0.25	1.6	0.25	19	2.9
F11	155	1.0	0.15	1.1	0.17	11	1.7

Table 13.

Extrapolated annual doses (H_p(10), H_p(3), H_p(0.07)) for NM staff performing ¹⁷⁷Lu synthesis

Participants	Annual activity (A)	< Hp(10)/A >	Annual Hp(10)	< Hp(3)/A >	Annual Hp(3)	< Hp(0.07)/A >	Annual Hp(0.07)
	[GBq]	[µSv/GBq]	[mSv]	[µSv/GBq]	[mSv]	[µSv/GBq]	[mSv]
D1	1348	0.4	0.5	0.4	0.5	33	44
D2	1077	0.4	0.5	0.5	0.5	34	37
I3	262	0.7	0.2	0.7	0.2	2.9	1
I5	262	0.6	0.2	0.6	0.2	5.7	1
K1	1620	0.3	0.4	0.3	0.4	45	72

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 H_p(10) can reach nearly 3 mSv, and H_p(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.

Discussion

Although well-characterized and sensitive detectors have been used to monitor occupational doses in NM departments, the whole-body and eye lens doses we measured for the specific isotopes under study often remained below the DL (50 µSv), even with monthly monitoring for ⁶⁸Ga or over several treatment cycles for ¹⁷⁷Lu and ¹³¹I. From the collected routine dosimetry data we could observe that the total monthly whole-body doses (considering all the isotopes handled by the respective participant) were typically higher than the DL applied in this study. The variation in extremity doses between hospitals for the same radionuclide can largely be explained by the specific tasks performed and the working procedures applied within those tasks. Based on our results, we can confirm that the use of automatic synthesis and dispensing significantly reduces the dose to personnel. There is a large variation in academic background of the staff that collaborated in the measurements, depending on the hospitals. For ¹⁷⁷Lu, the synthesis, labeling and QC are mainly done by NM technologists (hospitals D, E, I and K), only in hospital J this is done by a radiopharmacist. For the administration of ¹⁷⁷Lu, physicians are involved in hospitals E, F and I, while in hospitals D and J this is also done by NM technologists. In hospital D, also 1 medical physicist was involved in the preparation, QC and administration of ¹⁷⁷Lu. For ⁶⁸Ga, the synthesis, labeling and QC were performed by NM technologists in hospitals D and E, while it was done by lab technicians in hospitals C, G and H. In hospital D again 1 medical physicist participated. The ⁶⁸Ga injections were performed by NM technologists (hospitals C and D), by lab technicians (hospital G), by nurses (hospital F) or by physicians (hospitals E and H). The number of participants per category are too low to make a sound conclusion on what is the effect of the staff’s academic background on the obtained dose data.

In the review paper by Kollaard et al., five studies were identified that reported fingertip doses for ¹⁷⁷Lu ranging from 1 to 44 µSv/GBq [18]. These findings are consistent with the average maximum fingertip dose observed in this study, which is 30 µSv/GBq, with a range of 5.5–92.4 µSv/GBq. For the unpacking and administration of ¹³¹I pills, documented fingertip doses vary between 50 and 7040 µSv/GBq [21]. This extensive range encompasses the average maximum fingertip dose of 260 µSv/GBq, with a specific range of 20–743 µSv/GBq reported in this study. Additionally, a recent study by Wrzesien et al. conducted a small-scale measurement campaign to evaluate fingertip doses in a NM department involved in the preparation and administration of ⁶⁸Ga-DOTA-TATE [22]. The results from Wrzesien’s study were comparable to those in this study, with the highest average fingertip dose being approximately 4 mSv/GBq for elution and labeling of ⁶⁸Ga, 40 mSv/GBq for dispensing, and 1.3 mSv/GBq for technologists administering the doses.

On average, ⁶⁸Ga activities monitored in this study result in about 40 times higher finger doses per manipulated activity compared to other isotopes, with variations ranging from 3 to 155 times. Most participants handle less than 2% of their total activity coming from ⁶⁸Ga, with the majority coming from ^99mTc and ¹⁸F. An exception in this study is participant G2, who handles a higher workload for ⁶⁸Ga, while only 25% for ^99mTc, ~ 20% for ⁸²Rb and ¹³¹I, and 10% for ⁹⁰Y.

For ¹⁷⁷Lu administrations, extremity doses are 7–25 times higher than those coming from other isotopes, but this analysis includes only 2 participants, i.e. F2 and F11 who primarily handle ^99mTc and ¹⁸F (~ 90%). Participants preparing and dispensing ¹⁷⁷Lu mainly work with this radionuclide, contributing 40–90% of their handled activity, but only 5–25% of their routine finger dose, indicating that ¹⁷⁷Lu preparation contributes less to the finger dose than other isotope preparations.

Generalizing these results is difficult due to the variability in isotope handling practices and personal habits. The use of different detectors between this study and routine practice adds uncertainty, particularly for beta-particle exposure from ⁶⁸Ga, as for this study detectors are used with an improved response for beta-particles. Moreover, routine ring dosemeters might sometimes be forgotten or affected by contamination, complicating its dose determination. A study limitation is the often-limited dose data from only 2 datasets per participant, hindering long-term isotope contribution assessment. More datasets per participant would strengthen the analysis, but practical constraints made this difficult. The burden of using multiple dosemeters and detailed activity recording, along with low frequency of ¹⁷⁷Lu therapy, further limited the available data.

As observed in many other studies, maximum finger doses are reached on the fingertips. For ⁶⁸Ga this maximum dose is mostly observed on the non-dominant hand, while for ¹⁷⁷Lu the working practice results in a more equal distribution in dose values across both hands and the different positions. Additionally, we could confirm that the use of the ring dosemeter with a correction factor of 5 is recommended to estimate the maximum dose to the fingertips.

The evaluation of annual occupational doses, calculated by multiplying individual maximum doses per manipulated activity with estimated yearly activity, shows that for ¹⁷⁷Lu, these annual extremity doses remain well below the specific annual dose limits and even below the recommended monitoring limit (i.e. 1/3^rd of the annual dose limit). However, more care is needed for ⁶⁸Ga synthesis and dispensing, as some participants’ extrapolated annual H_p(0.07) values exceeded the 500mSv annual limit. Considering that ⁶⁸Ga typically represents only a small part of the total workload, a non-negligeable contribution from other isotopes should also be added to this annual extremity dose. Additionally, the annual eye lens dose approaches the recommended monitoring limit of 6 mSv and specific attention should be paid to eye lens doses during QC of ⁶⁸Ga radiopharmaceuticals. It should also be noted that all measurement values below the DL have been set to 50 µSv, meaning that mainly for whole-body doses and eye lens doses, these extrapolated yearly doses can be considered as conservative estimations.

Conclusion

This study’s measurement campaigns across various European countries have provided new and extensive occupational dosimetry data for  NM staff handling ⁶⁸Ga and ¹⁷⁷Lu radiopharmaceuticals and to a lesser extent also for ¹³¹I radiopharmaceuticals. For staff working in radiopharmacy hot labs, the preparation, labeling and dispensing of ¹⁷⁷Lu contribute less to the total finger dose compared to other isotopes. A conservative estimation of annual occupational doses indicates that the manipulation of ¹⁷⁷Lu has a limited impact on reaching the annual dose limits for whole-body, eye lens and extremity doses.

However, careful monitoring of hand and finger exposure is essential for all radiopharmaceuticals. The contribution of ⁶⁸Ga radiopharmaceuticals to finger doses is significantly higher compared to other isotopes, particularly during elution, synthesis and dispensing. There is a risk of reaching the annual dose limit for these activities. It is also recommended to monitor the eye lens dose during these procedures, at least for a specific period, to ensure accurate dose estimation and individual risk assessment.

Author contributions

LS has made substantial contribution to the conception and design of the work, the analysis and interpretation of the data and has drafted and revised the manuscript. EA, LB, NC, YD, FDM, ALM, RM, CT, SVdB, HZ, VS all contributed to the organization and collection of data in the participating centers. They all revised the manuscript. WS prepared and read all the dosemeter sets for the measurements in the participating centers. FV has made substantial contribution to the analysis of the data and revised the manuscript.

Funding

Some of the authors have received funding for this project from Euratom’s research and innovation programme 2019–20 under grant agreement no. 945196.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the local Medical ethics committees. Every participant received an information letter and signed an informed consent before participation. Only pseudonymised data will be used for analysis of the data and in any documentation, reports or publication about the study.

Consent for publication

Not applicable, no individual person data submitted in the paper.

Competing interests

The authors declare that they have no competing interests” in this section.