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.

Assessment of fluence- and dose-averaged linear energy transfer with passive luminescence detectors in clinical proton beams.

This work investigates the use of passive luminescence detectors to determine different types of averaged linear energy transfer (LET-) for the energies relevant to proton therapy. The experimental results are compared to reference values obtained from Monte Carlo simulations.Optically stimulated luminescence detectors (OSLDs), fluorescent nuclear track detectors (FNTDs), and two different groups of thermoluminescence detectors (TLDs) were irradiated at four different radiation qualities.

New optically stimulated luminescence dosimetry film optimized for energy dependence guided by Monte Carlo simulations.

Optically stimulated luminescence (OSL) film dosimeters, based on BaFBr:Euphosphor material, have major dosimetric advantages such as dose linearity, high spatial resolution, film re-usability, and immediate film readout. However, they exhibit an energy-dependent over-response at low photon energies because they are not made of tissue-equivalent materials. In this work, the OSL energy-dependent response was optimized by lowering the phosphor grain size and seeking an optimal choice of phosphor concentration and film thickness to achieve sufficient signal sensitivity.

Extended in-field and out-of-field validation of a compact Monte Carlo model of an IBA PROTEUSONE proton beam in TOPAS/GEANT4.

This study evaluates a compact Monte Carlo (MC) model of a pencil beam scanning clinical proton beam using TOPAS to estimate the dose out-of-field (OOF). Compact modelling means that the model starts from a pristine proton beam at the nozzle exit, customised based on acceptance and commissioning data, instead of modelling the full treatment head and room.: First, in-field validation tests were performed.

Complete patient exposure during paediatric brain cancer treatment for photon and proton therapy techniques including imaging procedures.

Background: In radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment.

Materials And Methods: Organ doses were calculated for treatment of a diffuse midline glioma (50.

Challenges and opportunities for proton therapy during pregnancy.

During pregnancy, the use of radiation therapy for cancer treatment is often considered impossible due to the assumed associated fetal risks. However, suboptimal treatment of pregnant cancer patients and unjustifiable delay in radiation therapy until after delivery can be harmful for both patient and child. In non-pregnant patients, proton-radiation therapy is increasingly administered because of its favorable dosimetric properties compared with photon-radiation therapy.

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.

Calibration and time fading characterization of a new optically stimulated luminescence film dosimeter.

Background: Optically stimulated luminescence (OSL) dosimeters produce a signal linear to the dose, which fades with time due to the spontaneous recombination of energetically unstable electron/hole traps. When used for radiotherapy (RT) applications, fading affects the signal-to-dose conversion and causes an error in the final dose measurement. Moreover, the signal fading depends to some extent on treatment-specific irradiation conditions such as irradiation times.

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.

Development of a computational pregnant female phantom and calculation of fetal dose during a photon breast radiotherapy.

Background: The incidence of carcinoma during pregnancy is reported to be 1:1000-1:1500 pregnancies with the breast carcinoma being the most commonly diagnosed. Since the fetus is most sensitive to ionizing radiation during the first two trimesters, there are mixed clinical opinions and no uniform guidelines on the use of radiotherapy during pregnancy. Within this study the pregnant female phantom in the second trimester, that can be used for radiotherapy treatment planning (as DICOM data), Monte Carlo simulations (as voxelized geometry) and experimental dosimetry utilizing 3D printing of the molds (as .

EURADOS REM-COUNTER INTERCOMPARISON AT MAASTRO PROTON THERAPY CENTRE: COMPARISON WITH LITERATURE DATA.

The Maastro Proton Therapy Centre is the first European facility housing the Mevion S250i Hyperscan synchrocyclotron. The proximity of the accelerator to the patient, the presence of an active pencil beam delivery system downstream of a passive energy degrader and the pulsed structure of the beam make the Mevion stray neutron field unique amongst proton therapy facilities. This paper reviews the results of a rem-counter intercomparison experiment promoted by the European Radiation Dosimetry Group at Maastro and compares them with those at other proton therapy facilities.

Out-of-Field Doses Produced by a Proton Scanning Beam Inside Pediatric Anthropomorphic Phantoms and Their Comparison With Different Photon Modalities.

Since 2010, EURADOS Working Group 9 (Radiation Dosimetry in Radiotherapy) has been involved in the investigation of secondary and scattered radiation doses in X-ray and proton therapy, especially in the case of pediatric patients. The main goal of this paper is to analyze and compare out-of-field neutron and non-neutron organ doses inside 5- and 10-year-old pediatric anthropomorphic phantoms for the treatment of a 5-cm-diameter brain tumor. Proton irradiations were carried out at the Cyclotron Centre Bronowice in IFJ PAN Krakow Poland using a pencil beam scanning technique (PBS) at a gantry with a dedicated scanning nozzle (IBA Proton Therapy System, Proteus 235).

Experimental Validation of an Analytical Program and a Monte Carlo Simulation for the Computation of the Far Out-of-Field Dose in External Beam Photon Therapy Applied to Pediatric Patients.

Background: The out-of-the-field absorbed dose affects the probability of primary second radiation-induced cancers. This is particularly relevant in the case of pediatric treatments. There are currently no methods employed in the clinical routine for the computation of dose distributions from stray radiation in radiotherapy.

Validation of a Monte Carlo Framework for Out-of-Field Dose Calculations in Proton Therapy.

Proton therapy enables to deliver highly conformed dose distributions owing to the characteristic Bragg peak and the finite range of protons. However, during proton therapy, secondary neutrons are created, which can travel long distances and deposit dose in out-of-field volumes. This out-of-field absorbed dose needs to be considered for radiation-induced secondary cancers, which are particularly relevant in the case of pediatric treatments.

In vitro dose effect relationships of actinium-225- and lutetium-177-labeled PSMA-I&T.

Purpose: Targeting the prostate-specific membrane antigen (PSMA) using lutetium-177-labeled PSMA-specific tracers has become a very promising novel therapy option for prostate cancer (PCa). The efficacy of this therapy might be further improved by replacing the β-emitting lutetium-177 with the α-emitting actinium-225. Actinium-225 is thought to have a higher therapeutic efficacy due to the high linear energy transfer (LET) of the emitted α-particles, which can increase the amount and complexity of the therapy induced DNA double strand breaks (DSBs).

Joint EURADOS WG9-WG11 rem-counter intercomparison in a Mevion S250i proton therapy facility with Hyperscan pulsed synchrocyclotron.

Objective Proton therapy is gaining popularity because of the improved dose delivery over conventional radiation therapy. The secondary dose to healthy tissues is dominated by secondary neutrons. Commercial rem-counters are valuable instruments for the on-line assessment of neutron ambient dose equivalent (H*(10)).

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.

Out-of-field doses in pediatric craniospinal irradiations with 3D-CRT, VMAT, and scanning proton radiotherapy: A phantom study.

Purpose: Craniospinal irradiation (CSI) has greatly increased survival rates for patients with a diagnosis of medulloblastoma and other primitive neuroectodermal tumors. However, as it includes exposure of a large volume of healthy tissue to unwanted doses, there is a strong concern about the complications of the treatment, especially for the children. To estimate the risk of second cancers and other unwanted effects, out-of-field dose assessment is necessary.

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.

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.

Targeted alpha therapy: a critical review of translational dosimetry research with emphasis on actinium-225.

This review provides a general overview of the current achievements and challenges in translational dosimetry for targeted alpha therapy (TAT). The concept of targeted radionuclide therapy (TRNT) is described with an overview of its clinical applicability and the added value of TAT is discussed. For TAT, we focused on actinium-225 (225Ac) as an example for alpha particle emitting radionuclides and their features, such as limited range within tissue and high linear energy transfer, which make alpha particle emissions more effective in targeted killing of tumour cells compared to beta radiation.

Cellular dosimetry of [Lu]Lu-DOTA-[Tyr]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 [Lu]Lu-DOTA-[Tyr]octreotate (Lu-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.