Occupational radiation exposure assessment during the management of [68Ga]Ga-DOTA-TOC

Background: Since it was first approved in Europe in 2016, the gallium-68 (68Ga) radiopharmaceutical [68Ga]Ga-DOTA-TOC has been widely used for imaging of somatostatin receptor (SSTR) positive tumours using positron emission tomography-computed tomography (PET/CT). Significant patient benefits have been reported, so its use is rapidly increasing. However, few studies have been published regarding occupational doses to nuclear medicine personnel handling this radiopharmaceutical, despite its manual usage at low distances from the skin and the beta-emission decay scheme, which may result in an increased absorbed dose to their hands. In this context, this study aims to analyse the occupational exposure during the administration of [68Ga]Ga-DOTA-TOC for PET/CT imaging. For this purpose, extremity, eye lens and whole-body dosimetry in terms of Hp(0.07), Hp(3) and Hp(10), respectively, was conducted on six workers with both thermoluminescent dosimeters, and personal electronic dosimeters. Results: The non-dominant hand is more exposed to radiation than the dominant hand, with the thumb and the index fingertip being the most exposed sites on this hand. Qualitative analysis showed that when no shielding is used during injection, doses increase significantly more in the dominant than in the non-dominant hand, so the use of shielding is strongly recommended. While wrist dosimeters may significantly underestimate doses to the hands, placing a ring dosimeter at the base of the ring or middle finger of the non-dominant hand may give a valuable estimation of maximum doses to the hands if at least a correction factor of 5 is applied. Personal equivalent doses for the eyes did not result in measurable values (i.e., above the lowest detection limit) for almost all workers. The extrapolated annual dose estimations showed that there is compliance with the annual dose limits during management of [68Ga]Ga-DOTA-TOC for diagnostics with PET in the hospital included in this study. Conclusions: Imaging with [68Ga]Ga-DOTA-TOC is a safe process for the workers performing the administration of the radiopharmaceutical, including intravenous injection to the patient and the pre- and post-activity control, as it is highly unlikely that annual dose limits will be exceeded if good working practices and shielding are used.Euratom research and training programme 2019?2020 under Grant Agree? ment N? 945196 (SINFONIA Projec

Cellular dosimetry of [177Lu]Lu-DOTA-[Tyr3]octreotate radionuclide therapy: the impact of modeling assumptions on the correlation with in vitro cytotoxicity

Background: Survival and linear-quadratic model fitting parameters implemented in treatment planning for targeted radionuclide therapy depend on accurate cellular dosimetry. Therefore, we have built a refined cellular dosimetry model for [177Lu]Lu-DOTA-[Tyr3]octreotate (177Lu-DOTATATE) in vitro experiments, accounting for specific cell morphologies and sub-cellular radioactivity distributions. Methods: Time activity curves were measured and modeled for medium, membrane-bound, and internalized activity fractions over 6 days. Clonogenic survival assays were performed at various added activities (0.1–2.5 MBq/ml). 3D microscopy images (stained for cytoplasm, nucleus, and Golgi) were used as reference for developing polygonal meshes (PM) in 3DsMax to accurately render the cellular and organelle geometry. Absorbed doses to the nucleus per decay (S values) were calculated for 3 cellular morphologies: spheres (MIRDcell), truncated cone-shaped constructive solid geometry (CSG within MCNP6.1), and realistic PM models, using Geant4-10.03. The geometrical set-up of the clonogenic survival assays was modeled, including dynamic changes in proliferation, proximity variations, and cell death. The absorbed dose to the nucleus by the radioactive source cell (self-dose) and surrounding source cells (cross-dose) was calculated applying the MIRD formalism. Finally, the correlation between absorbed dose and survival fraction was fitted using a linear dose-response curve (high α/β or fast sub-lethal damage repair half-life) for different assumptions, related to cellular sha

Effective detective quantum efficiency for two mammography systems: measurement and comparison against established metrics

The aim of this paper was to illustrate the value of the new metric effective detective quantum efficiency (eDQE) in relation to more established measures in the optimization process of two digital mammography systems. The following metrics were included for comparison against eDQE: detective quantum efficiency (DQE) of the detector, signal difference to noise ratio (SdNR), and detectability index (d') calculated using a standard nonprewhitened observer with eye filter.status: publishe

Effective detective quantum efficiency (eDQE) and effective noise equivalent quanta (eNEQ) for system optimization purposes in digital mammography

Effective detective quantum efficiency (eDQE) and effective noise equivalent quanta (eNEQ) were recently introduced to broaden the notion of DQE and NEQ by including system parameters such as focus blurring and system scatter rejection methods. This work investigates eDQE and eNEQ normalized for mean glandular dose (eNEQ MGD ) as a means to characterize and select optimal exposure parameters for a digital mammographic system. The eDQE was measured for three anode/filter combinations, with and without anti-scatter grid and for four thicknesses of poly(methylmethacrylate) (PMMA). The modulation transfer function used to calculate eDQE and eNEQ was measured from an edge positioned at 20,40,60,70 mm above the table top without scattering material in the beam. The grid-in eDQE results for all A/F settings were generally larger than those for grid-out. Contrarily, the eNEQ MGD results were higher for grid-out than grid- in, with a maximum difference of 61% among all A/F combinations and PMMA thicknesses. The W/Rh combination gave the highest eNEQ MGD for all PMMA thicknesses compared to the other A/F combinations (for grid-in and grid-out), supporting the results of alternative methods (e.g. the signal difference to noise ratio method). The eNEQ MGD was then multiplied with the contrast obtained from a 0.2mm Al square, resulting in a normalized quantity that was higher for the W/Rh combination than for the other A/F combinations. In particular, the results for the W/Rh combination were greater for the grid-in case. Furthermore, these results showed close agreement with a non-prewhitened match filter with eye response model observer (d’) normalized for MGD.status: publishe

Tailoring automatic exposure control toward constant detectability in digital mammography

The automatic exposure control (AEC) modes of most full field digital mammography (FFDM) systems are set up to hold pixel value (PV) constant as breast thickness changes. This paper proposes an alternative AEC mode, set up to maintain some minimum detectability level, with the ultimate goal of improving object detectability at larger breast thicknesses.received: 2014-12-02 revised: 2015-03-30 accepted: 2015-05-10 published: 2015-06-09status: publishe

Model observer detectability as a substitute for contrast detail analysis in routine digital mammography quality control

This work investigated the substitution of CDMAM contrast detail (c-d) analysis with detectability (d’) from a non- prewhitening eye filter model observer (NPWE) for routine quality control (QC). Routinely acquired QC data for 53 systems were analyzed: 13 computed radiography (CR) and 40 integrated detector (DR) systems. For a given system, threshold gold thickness from the c-d analysis (T) was calculated from 16 images and compared against d’ calculated for 0.1 and 0.25 mm diameter discs. The d’ data were calculated from the routine 50 mm PMMA AEC image and the measured pre-sampling detector modulation transfer function (MTF). Threshold gold thickness T and d’ were plotted as function of MGD and compared. The Fuji CR and the Agfa CR systems had the highest T values compared to the other systems. The Hologic systems were found to have a low value of T, compared to the other systems, for both disc diameters. The NPWE results reflected the performance seen for T data for the majority of the systems with the exception of the Fuji CR and Konica CR systems. The Hologic systems gave unexpectedly low d’ results or unexpectedly low T values. The correspondence between the two quality indices was examined with the Pearson correlation statistical test. This test was not applicable to the GE Essential systems because all systems are grouped together at the same working point so the result of r is about 0. For all other groups of systems the test gave good results (larger than -0.65).status: publishe

A Review on Tumor Control Probability (TCP) and Preclinical Dosimetry in Targeted Radionuclide Therapy (TRT)

Targeted radionuclide therapy (TRT) uses radiopharmaceuticals to specifically irradiate tumor cells while sparing healthy tissue. Response to this treatment highly depends on the absorbed dose. Tumor control probability (TCP) models aim to predict the tumor response based on the absorbed dose by taking into account the different characteristics of TRT. For instance, TRT employs radiation with a high linear energy transfer (LET), which results in an increased effectiveness. Furthermore, a heterogeneous radiopharmaceutical distribution could result in a heterogeneous dose distribution at a tissue, cellular as well as subcellular level, which will generally reduce the tumor response. Finally, the dose rate in TRT is protracted, relatively low, and variable over time. This allows cells to repair more DNA damage, which may reduce the effectiveness of TRT. Within this review, an overview is given on how these characteristics can be included in TCP models, while some experimental findings are also discussed. Many parameters in TCP models are preclinically determined and TCP models also play a role in the preclinical stage of radiopharmaceutical development; however, this all depends critically on the calculated absorbed dose. Accordingly, an overview of the existing preclinical dosimetry methods is given, together with their limitation and applications. It can be concluded that although the theoretical extension of TCP models from external beam radiotherapy towards TRT has been established quite well, the experimental confirmation is lacking. Thus, requiring additional comprehensive studies at the sub-cellular, cellular, and organ level, which should be provided with accurate preclinical dosimetry

The use of detectability indices as a means of Automatic Exposure Control for a digital mammography system

This work examines the use of a detectability index to control an Automatic Exposure Control (AEC) system for an amorphous-Selenium digital mammography detector. The default AEC mode for the system was evaluated using homogeneous poly(methyl methacrylate) (PMMA) plates of thickness 20, 40, 60 and 70 mm to find the tube potential and anode/filter settings selected by the system. Detectability index (d’) using a non-prewhitened model observer with eye filter (NPWE) was calculated for these beam qualities as a function of air kerma at the detector. AEC settings were calculated that gave constant d’ as a function of beam quality for a homogeneous background; a target d’ was used that ensured the system passed the achievable image quality criterion for the 0.1 mm diameter disc in the European Guidelines. Threshold gold thickness was measured using the CDMAM test object as a function of beam quality for the AEC mode, which held pixel value (PV) constant, and for the constant d’ mode. Threshold gold thickness for the 0.1 mm disc increased by a factor of 2.18 for the constant PV mode, while constant d’ mode held threshold gold thickness constant to within 7% and signal-difference-to-noise-ratio (SdNR) constant to within 5%. The constant d’ settings derived for homogeneous images were then applied to a phantom with a structured background. Threshold gold thickness for the 0.13 mm disc increased by a factor of 1.90 for the constant PV mode, while constant d’ mode held threshold gold thickness constant within 38% for 0.13 mm disk.status: publishe