The Emission of Internal Conversion Electrons Rather Than Auger Electrons Increased the Nucleus-Absorbed Dose for Tb Compared with Lu with a Higher Dose Response for [Tb]Tb-DOTA-LM3 Than for [Tb]Tb-DOTATATE.

Preclinical data have shown that Tb-labeled peptides targeting the somatostatin receptor are therapeutically more effective for peptide receptor radionuclide therapy than are their Lu-labeled counterparts. To further substantiate this enhanced therapeutic effect, we performed cellular dosimetry to quantify the absorbed dose to the cell nucleus and compared dose-response curves to evaluate differences in relative biological effectiveness in vitro. CA20948 cell survival was assessed after treatment with [Tb]Tb- and [Lu]Lu-DOTATATE (agonist) and with [Tb]Tb- and [Lu]Lu-DOTA-LM3 (antagonist) via a clonogenic assay.

Object and person tracking systems to enable extremity dosimetry in nuclear medicine using computational methods.

Nuclear medicine (NM) professionals are potentially exposed to high doses of ionising radiation, particularly in the skin of the hands. Ring dosimeters are used by the workers to ensure extremity doses are kept below the legal limits. However, ring dosimeters are often susceptible to large uncertainties, so it is difficult to ensure a correct measurement using the traditional occupational monitoring methods.

Joint EURADOS-EANM initiative for an advanced computational framework for the assessment of external dose rates from nuclear medicine patients.

Background: In order to ensure adequate radiation protection of critical groups such as staff, caregivers and the general public coming into proximity of nuclear medicine (NM) patients, it is necessary to consider the impact of the radiation emitted by the patients during their stay at the hospital or after leaving the hospital. Current risk assessments are based on ambient dose rate measurements in a single position at a specified distance from the patient and carried out at several time points after administration of the radiopharmaceutical to estimate the whole-body retention. The limitations of such an approach are addressed in this study by developing and validating a more advanced computational dosimetry approach using Monte Carlo (MC) simulations in combination with flexible and realistic computational phantoms and time activity distribution curves from reference biokinetic models.

Radiation exposure assessment of nuclear medicine staff administering [Lu]Lu-DOTA-TATE with active and passive dosimetry.

Background: The use of lutetium-177 (Lu)-based radiopharmaceuticals in peptide receptor nuclear therapy is increasing, but so is the number of nuclear medicine workers exposed to higher levels of radiation. In recent years, [Lu]Lu-DOTA-TATE has begun to be widely used for the treatment of neuroendocrine tumours. However, there are few studies evaluating the occupational radiation exposure during its administration, and there are still some challenges that can result in higher doses to the staff, such as a lack of trained personnel or fully standardised procedures.

Heterogeneity of absorbed dose distribution in kidney tissues and dose-response modelling of nephrotoxicity in radiopharmaceutical therapy with beta-particle emitters: A review.

Absorbed dose heterogeneity in kidney tissues is an important issue in radiopharmaceutical therapy. The effect of absorbed dose heterogeneity in nephrotoxicity is, however, not fully understood yet, which hampers the implementation of treatment optimization by obscuring the interpretation of clinical response data and the selection of optimal treatment options. Although some dosimetry methods have been developed for kidney dosimetry to the level of microscopic renal substructures, the clinical assessment of the microscopic distribution of radiopharmaceuticals in kidney tissues currently remains a challenge.

Biophysical characterization of collimated and uncollimated fields in pencil beam scanning proton therapy.

. The lateral dose fall-off in proton pencil beam scanning (PBS) technique remains the preferred choice for sparing adjacent organs at risk as opposed to the distal edge due to the proton range uncertainties and potentially high relative biological effectiveness. However, because of the substantial spot size along with the scattering in the air and in the patient, the lateral penumbra in PBS can be degraded.

Impact of the implementation of the new radiation quantities recommended by ICRU/ICRP for practical use in interventional radiology: a Monte Carlo study.

The International Commission on Radiation Units and Measurements (ICRU) proposed a new set of operational quantities for radiation protection for external radiation in its Report Committee 26 (). The new proposal aims to improve the coherence between the operational quantities and the definitions of the protection quantities in the recommendations of the International Commission on Radiological Protection set out in 2007 (). It is expected that this change in operational quantities will impact current dosimeter designs.

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

Background: Since it was first approved in Europe in 2016, the gallium-68 (Ga) radiopharmaceutical [Ga]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.

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.

Gamma counting protocols for the accurate quantification of Ac and Bi without the need for a secular equilibrium between parent and gamma-emitting daughter.

Background: Quantification of actinium-225 through gamma counter measurements, when there is no secular equilibrium between actinium-225 and its gamma emitting daughters bismuth-213 and/or francium-221, can provide valuable information regarding the possible relocation of recoiled daughters such that related radiotoxicity effects can be evaluated. This study proposes a multiple time-point protocol using the bismuth-213 photopeak with measurements before secular equilibrium between actinium-225 and bismuth-213, and a single time-point protocol using both the francium-221 and bismuth-213 photopeak while assuming secular equilibrium between actinium-225 and francium-221 but not between bismuth-213 and actinium-225.

Results: Good agreement (i.

A Realistic Multiregion Mouse Kidney Dosimetry Model to Support the Preclinical Evaluation of Potential Nephrotoxicity of Radiopharmaceutical Therapy.

Suborgan absorbed dose estimates in mouse kidneys are crucial to support preclinical nephrotoxicity analyses of α- and β-particle-emitting radioligands exhibiting a heterogeneous activity distribution in the kidneys. This is, however, limited by the scarcity of reference dose factors (S values) available in the literature for specific mouse kidney tissues. A computational multiregion model of a mouse kidney based on high-resolution MRI data from a healthy mouse kidney was developed.

CORRELATION BETWEEN ROUTINE PERSONAL DOSIMETRY READING AND THE DOSE TO THE BRAIN OF INTERVENTIONAL STAFF.

This study aimed to evaluate the relationship between the brain absorbed dose and personal dosimetry readings in interventional cardiologists. Interventional procedures were replicated using Monte Carlo simulations (MCNP 6) with anthropomorphic phantoms representing both operator and patient. Absorbed doses were evaluated for 10 predefined regions of the operator's brain as well as for dosemeters at chest and neck level.

Modelling SPECT auto-contouring acquisitions for Lu & I molecular radiotherapy using new developments in Geant4/GATE.

Purpose: Monte Carlo modelling of SPECT imaging in Molecular Radiotherapy can improve activity quantification. Until now, SPECT modelling with GATE only considered circular orbit (CO) acquisitions. This cannot reproduce auto-contour acquisitions, where the detector head moves close to the patient to improve image resolution.

Therapeutic efficacy of heterogeneously distributed radiolabelled peptides: Influence of radionuclide choice.

Purpose: To model dose-response relationships for in vivo experiments with radiolabelled peptides enabling maximum therapeutic efficacy while limiting toxicity to kidney and bone marrow.

Methods: A multiregional murine kidney phantom, with a kinetic model for cortex and outer medulla distribution, were used to predict renal toxicity. Maximum tolerated activities to avoid nephrotoxicity (at 40 Gy Biological Effective Dose BED) and hematologic toxicity (at 2 Gy) were compared.

Assessment of mouse-specific pharmacokinetics in kidneys based on I activity measurements using micro-SPECT.

Background: In order to acquire accurate drug pharmacokinetic information, which is required for tissue dosimetry, micro-SPECT must be quantitative to allow for an accurate assessment of radioligand activity in the relevant tissue. This study investigates the feasibility of deriving accurate mouse-specific time-integrated drug pharmacokinetic data in mouse kidneys from activity measurements using micro-SPECT.

Methods: An animal experiment was carried out to evaluate the accuracy of I activity quantification in mouse kidneys (mean tissue volume of 0.

Microdosimetric characterization of a clinical proton therapy beam: comparison between simulated lineal energy distributions in spherical water targets and experimental measurements with a silicon detector.

. Treatment planning based on computer simulations wasproposed to account for the increased relative biological effectiveness (RBE) of proton radiotherapy beams near to the edges of the irradiated volume. Since silicon detectors could be used to validate the results of these simulations, it is important to explore the limitations of this comparison.

Intercomparison and performance assessment of radionuclide calibrators used in nuclear medicine departments in Serbia.

The purpose of this work is to assess accuracy and compare the performance of radionuclide calibrators (RNCs) used in nuclear medicine departments in Serbia. Testing of the RNCs included verification of measurement accuracy, as well as analysis of routinely used quality control protocols, by using the certified radioactivity standards (Co, Cs). RNCs performances were assessed with Tc through comparison of reference value for radionuclide activity and RNC measurements.

Comparison between the results of a recently-developed biological weighting function (V79-RBEBWF) and theclonogenic survival RBEof other repair-competent asynchronized normoxic mammalian cell lines and ions not used for the development of the model.

728 simulated microdosimetric lineal energy spectra (26 different ions betweenH andU, 28 energy points from 1 to 1000 MeV/n) were used in combination with a recently-developed biological weighting function (Parisi20201361-6560) and 571 publishedclonogenic survival curves in order to: (1) assess prediction intervals for theresults by deriving an empirical indication of the experimental uncertainty from the dispersion in thehamster lung fibroblast (V79) data used for the development of the biophysical model; (2) explore the possibility of modeling the relative biological effectiveness (RBE) of the 10% clonogenic survival of asynchronized normoxic repair-competent mammalian cell lines other than the one used for the development of the model (V79); (3) investigate the predictive power of the model through a comparison betweenresults anddata for 10 ions not used for the development of the model. At first, different strategies for the assessment of theprediction intervals were compared. The possible sources of uncertainty responsible for the dispersion in thedata were also shortly reviewed.

Modeling Early Radiation DNA Damage Occurring During Lu-DOTATATE Radionuclide Therapy.

The aim of this study was to build a simulation framework to evaluate the number of DNA double-strand breaks (DSBs) induced by in vitro targeted radionuclide therapy (TRT). This work represents the first step toward exploring underlying biologic mechanisms and the influence of physical and chemical parameters to enable a better response prediction in patients. We used this tool to characterize early DSB induction by Lu-DOTATATE, a commonly used TRT for neuroendocrine tumors.

Investigation of single-shot beam quality measurements using state of the art solid-state dosimeters for routine quality assurance applications in mammography.

Purpose: To assess if single shot acquisitions with solid-state dosimeters as well as Robson's method could replace ionization chambers for tube output and HVL measurements, saving medical physicists time.

Material And Methods: The energy responses of 4 solid-state dosimeters with automatic calculation of HVL were compared to ionization chamber measurements. Five anode/filter combinations were tested: Mo/Mo, Mo/Rh, Rh/Rh, W/Rh and W/Ag, from 24kVp to 35kVp.

Generation of clinical Lu SPECT/CT images based on Monte Carlo simulation with GATE.

Purpose: Patient-specific dosimetry in MRT relies on quantitative imaging, pharmacokinetic assessment and absorbed dose calculation. The DosiTest project was initiated to evaluate the uncertainties associated with each step of the clinical dosimetry workflow through a virtual multicentric clinical trial. This work presents the generation of simulated clinical SPECT datasets based on GATE Monte Carlo modelling with its corresponding experimental CT image, which can subsequently be processed by commercial image workstations.

Dosimetric Evaluation of the Effect of Receptor Heterogeneity on the Therapeutic Efficacy of Peptide Receptor Radionuclide Therapy: Correlation with DNA Damage Induction and In Vivo Survival.

Our rationale was to build a refined dosimetry model for Lu-DOTATATE in vivo experiments enabling the correlation of absorbed dose with double-strand break (DSB) induction and cell death. Somatostatin receptor type 2 expression of NCI-H69 xenografted mice, injected with Lu-DOTATATE, was imaged at 0, 2, 5, and 11 d. This expression was used as input to reconstruct realistic 3-dimensional heterogeneous activity distributions and tissue geometries of both cancer and heathy cells.

Two-dimensional real-time quality assurance dosimetry system using μ-AlO:C,Mg radioluminescence films.

Background And Purpose: There is a continual need for more accurate and effective dosimetric systems for quality assurance (QA) as radiotherapy evolves in complexity. The purpose of this project was to introduce a new system that minimally perturbs the main beam, while assessing its real time 2D dose-rate and field shapes. The system combined reusability, linear dose-rate response, and high spatial and time resolution in a single radiation detection technology that can be applied to surface dose estimation and QA.

Methodology to create 3D models of COVID-19 pathologies for virtual clinical trials.

We describe the creation of computational models of lung pathologies indicative of COVID-19 disease. The models are intended for use in virtual clinical trials (VCT) for task-specific optimization of chest x-ray (CXR) imaging. Images of COVID-19 patients confirmed by computed tomography were used to segment areas of increased attenuation in the lungs, all compatible with ground glass opacities and consolidations.

Radiation-induced lens opacities: Epidemiological, clinical and experimental evidence, methodological issues, research gaps and strategy.

In 2011, the International Commission on Radiological Protection (ICRP) recommended reducing the occupational equivalent dose limit for the lens of the eye from 150 mSv/year to 20 mSv/year, averaged over five years, with no single year exceeding 50 mSv. With this recommendation, several important assumptions were made, such as lack of dose rate effect, classification of cataracts as a tissue reaction with a dose threshold at 0.5 Gy, and progression of minor opacities into vision-impairing cataracts.