Dose estimates of occupational radiation exposure during radioguided surgery of [ 99m Tc]Tc-PSMA-labeled lymph nodes in recurrent prostate cancer

Background and objective [ 99m Tc]Tc-PSMA-based radioguided surgery (TPRS) represents a curative approach for localized relapse of prostate cancer. For its simplified regulatory permission, the radiation protection authorities require a 99m Tc activity below the exemption limit of 10 MBq at the time of surgery. Our aim was to determine the optimal amount of radioactivity (OAR) to comply with that limit and to estimate the maximum number of TPRS procedures per year and surgeon without triggering the full monitoring obligations. In this retrospective study, a dose rate meter was calibrated using measurements on phantoms and from recently injected (1 min p.i.) patients to determine the activity in the patient from measured dose rates. The effective half-life of [ 99m Tc]Tc-PSMA-I&S in patients was determined from repeated dose rate measurements up to 27 h p.i. to estimate dose parameters of relevance for radiation protection. External exposures of the surgeons were measured with personal dosimeters calibrated in Hp(10).


Background and objective
[ 99m Tc]Tc-PSMA-based radioguided surgery (TPRS) represents a curative approach for localized relapse of prostate cancer. For its simplified regulatory permission, the radiation protection authorities require a 99m Tc activity below the exemption limit of 10 MBq at the time of surgery.
Our aim was to determine the optimal amount of radioactivity (OAR) to comply with that limit and to estimate the maximum number of TPRS procedures per year and surgeon without triggering the full monitoring obligations.

Methods
In this retrospective study, a dose rate meter was calibrated using measurements on phantoms and from recently injected (1 min p.i.) patients to determine the activity in the patient from measured dose rates. The effective half-life of [ 99m

Summary
All radiation protection regulations are met with adherence to OAR recommended here without triggering the full monitoring obligations from radiation protection regulations.

INTRODUCTION
Prostate cancer (PCa) is the most frequent cancer in men with African ancestry as one main risk factor as well as population ageing, obesity and physical inactivity resulting in a yet increasing incidence [1,2]. The multidisciplinary therapeutic concept consists of surgery, radiotherapy, androgen deprivation therapy, and chemotherapy [3]. The incidence of a tumor recurring after primary curative therapy is up to 50%. Early detection of a tumor recurrence is crucial for a second attempt of curation. Improvements in mortality of prostate cancer are mainly attributed to the effective treatment of localized lesions which are nowadays detected at increasingly earlier stages [2].
According to the German Radiation Protection Act (StrlSchG), the overall responsibility under radiation protection law for the procedure lies with the authorized nuclear medicine physician as the board-certified expert in radiation protection. The prerequisites for the safe handling of ionizing radiation must be established according to the legal requirements. To assure this, estimates of the radiation dose levels and of the amounts of radioactivity have to be known for the different steps during the handling of unsealed radionuclides.
For radioguided surgery of sentinel lymph nodes, a simplified regulatory permission without the need for continuous radiation monitoring of all personal can be obtained in Germany. Therefore, the radiation protection authorities require a 99m Tc activity below the exemption limit of 10 MBq at the time of surgery and the surgeons' whole-body dose must certainly not exceed a total of 1 mSv 4 per year. The same conditions apply for a simplified regulatory permission for TPRS. As far as we know, there are no published data for the TPRS on relevant radiation protection parameters, in particular not on the effective half-life of intravenously injected [ 99m Tc]Tc-PSMA-I&S, not on the optimal activity to be applied, nor on the radiation exposure of the involved personal.
Thus, the aim of our analysis was to assess the unknown parameters by measurements and to estimate the radiation exposure for involved health professionals as well as the maximum number of TPRS procedures per year and surgeon without triggering the full monitoring obligations.

Patients
In this retrospective analysis, we included the first subsequent 8 patients who underwent [ 99m

Image analysis
Images were visually interpreted by 2 experienced nuclear medicine physicians who were also board-certified for CT reading. Physiological uptake in the kidneys, lacrimal and salivary glands, thyroid, liver, gall bladder, spleen, pancreas, digestive tract, kidneys, ureters, and urinary bladder was ignored. Focal uptake that could not be explained by physiological uptake or urinary excretion was interpreted suspicious of prostate cancer (PSMA-positive) [10]. Findings were classified in consensus. In cases where during primary reading at the end of the scan indeterminate results (e.g., tumor uptake vs. tracer excretion in the urinary tract) were present, additional imaging at the next 6 day was performed. Figure 1 shows an example of a [ 99m

Dose rate measurements and calibration for radioactivity levels
To estimate the amount of radioactivity in the patient as a function of time, dose rate measurements were carried out with a calibratable handheld dose rate meter (RadEye G10, Thermo Fisher Scientific Inc., Waltham, USA). It consists of an energy-compensated Geiger-Mueller tube with a measurement range of 0.5 to 100 mSv/h and an energy range of 50 keV to 3 MeV. A calibration factor was determined for this instrument to calculate the activity in the patient from measured dose rates. Therefore, repeated measurements were performed at 1 m distance on a cylindrical phantom (diameter 20 cm, height 20 cm) filled with 99m

Measurement of external radiation exposure
The involved surgeons were equipped with electronic personal dosimeters calibrated in Hp (10)

Estimated maximum number of permissible procedures
The expected dose rate at a given distance for a given applied activity was calculated using the

Calibration of the dose rate meter from phantom measurements and validation in patients
The amount of radioactivity A in the cylinder phantom as well as the dose rate DR measurements at time points t are reported in Table 1 together with the resulting calibration factor K and the corresponding measurement uncertainties. From this experiment, a calibration factor K of 0.013±0.001 permission to handle radioactivities above the exemption limit. Thus, the surgical staff is not subject to radiation protection monitoring.
In order to meet the regulatory requirements for a simplified approval we here estimate the level of occupational radiation exposure. Therefore we performed a calibration of the dose rate meter from phantom measurements with an additional validation in patients. This allowed us to estimate the effective half-life from dose rate measurements to determine the earliest time of surgery. To our best knowledge, there are no reports about such occupational radiation protection aspects for the personnel at present.
In a previous study [8], In some points, radiation protection aspects in TPRS differ from those in sentinel lymph node biopsy (SLNB). Similar to the established practice in SLNB [12], the use of radiation shielding of the surgeon is not practicable and does not seem necessary due to the low expected radiation exposure of surgery staff.
Our study may have some limitations. Even though the analyzed patients showed comparable results in terms of measurement accuracy, the small case number of 6 patients is certainly the main limitation of our study. In order to rapidly establish the method within the legal requirements, we had to waive the examination of a larger patient cohort.
Due to the hardware design of the dose rate meter, the geometric sensitivity may be inhomogeneous and thus affect the dose results. To account for this potential bias, we performed measurements both in a phantom as well as in patients and compared the results. From the strong agreement between the phantom experiment and patient data we see that the dose rate measurements are sufficient to give a reliable estimate of the amount of radioactivity within the patient at any time point. Furthermore, we observed a close correlation of staff exposure measurements by means of dosimeters as compared to the dose estimates from our model using patient-specific parameters.
It should be emphasized that in the present study the effective dose was considered and derived from dose rate estimates to whole-body, but not from partial body doses, especially those of the fingers. In contrast to the situation in SLNB of melanoma, where the injection site is resected, we consider the finger dose in TPRS to be negligible, because after systemic distribution of the tracer no highly concentrated radioactivity is expected in the surgical field.  Determination of the calibration factor from dose rate measurements on a cylinder phantom Table 2 Maximum number of annual TPRS operations of a surgeon assuming a mean duration of 1, 2, 3 or 4 h, respectively, in a mean distance of 0.25, 0.5, 0.75 or 1 m to the patient before reaching the dose limits of the different German radiation protection categories 16

Funding
There was no funding for this study.

Conflicts of interest/Competing interests
The authors declare, that they have no conflict of interest or competing interests.

Ethics approval
This retrospective study was performed in accordance with all relevant guidelines and regulations.
Based on the retrospective nature and a fully anonymized set of clinical data the need of an informed consent was waived by the institutional authorities.

Consent to publication
All authors agreed with the content and gave explicit consent for publication. All authors obtained consent from the responsible authorities at the institutes where the work has been carried out.

Availability of data and material
All individual de-identified data will be shared upon request.

Code availability
All software applications are mentioned in the section "Material and methods".