An international multi-center investigation on the accuracy of radionuclide calibrators in nuclear medicine theragnostics

Background: Personalized molecular radiotherapy based on theragnostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and therapeutic applications. This international multi-center study aims to investigate the clinical measurement accuracy of radionuclide calibrators for 7 radionuclides used in theragnostics: 99mTc, 111In, 123I, 124I, 131I, 177Lu, and 90Y. Methods: In total, 32 radionuclide calibrators from 8 hospitals located in the Netherlands, Belgium, and Germany were tested. For each radio

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

International audienceAbsorbed 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. This restricts the anatomical resolution of clinical dosimetry, which hinders a thorough clinical investigation of the impact of absorbed dose heterogeneity. The potential of absorbed dose–response modelling to support individual treatment optimization in radiopharmaceutical therapy is recognized and gaining attraction. However, biophysical modelling is currently underexplored for the kidney, where particular modelling challenges arise from the convolution of a complex functional organization of renal tissues with the function-mediated dose distribution of radiopharmaceuticals. This article reviews and discusses the heterogeneity of absorbed dose distribution in kidney tissues and the absorbed dose–response modelling of nephrotoxicity in radiopharmaceutical therapy. The review focuses mainly on the peptide receptor radionuclide therapy with beta-particle emitting somatostatin analogues, for which the scientific literature reflects over two decades of clinical experience. Additionally, detailed research perspectives are proposed to address various identified challenges to progress in this field

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 (57Co, 137Cs). RNCs performances were assessed with 99mTc through comparison of reference value for radionuclide activity and RNC measurements. Results of the intercomparison revealed that RNCs, 15 in total, are accurate within 10% in vial geometry and within 15% in syringe geometry. Most of them showed similar performance. The results revealed that container geometry is an important influencing parameter in the accuracy of activity measurement. Obtained results indicate a need for regular calibration and implementation of Quality Control program in order to achieve and maintain the accuracy of activity measurements in nuclear medicine

Secondary neutron doses in a proton therapy centre

The formation of secondary high-energy neutrons in proton therapy can be a concern for radiation protection of staff. In this joint intercomparative study (CERN, SCK•CEN and IBA/IRISIB/ULB), secondary neutron doses were assessed with different detectors in several positions in the Proton Therapy Centre, Essen (Germany). The ambient dose equivalent H*(10) was assessed with Berthold LB 6411, WENDI-2, tissue-equivalent proportional counter (TEPC) and Bonner spheres (BS). The personal dose equivalent Hp(10) was measured with two types of active detectors and with bubble detectors. Using spectral and basic angular information, the reference Hp(10) was estimated. Results concerning staffexposure show H*(10) doses between 0.5 and 1 nSv/monitoring unit in a technical room. The LB 6411 showed an underestimation of H*(10), while WENDI-2 and TEPC showed good agreement with the BS data. A large overestimation for Hp(10) was observed for the active personal dosemeters, while the bubble detectors showed only a slight overestimation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Secondary neutrons inside a proton therapy facility: MCNPX simulations compared to measurements performed with a Bonner Sphere Spectrometer and neutron H*(10) monitors

Neutron spectrometry measurements with an extended-range Bonner Sphere Spectrometer (BSS), as well as neutron H*(10) measurements using an extended-range rem meter WENDI-2, a conventional rem meter LB 6411 and a tissue-equivalent proportional counter, were performed inside and around the Fixed-Beam Treatment Room at the proton therapy facility of Essen, in Germany. The WENDI-2 stood out as the easiest detector for making accurate neutron H*(10) measurements, since its direct measurements were equivalent to the H*(10) rates obtained with the BSS. The measurements were also compared to simulation results obtained with MCNPX 2.7.0 using two different selections of physics models for the hadron interactions above 150 MeV: the Bertini & Dresner models and the CEM03 model. For neutron H*(10) rates outside the treatment room, factors of 1.6–1.8 were obtained between the results of the two simulations, the Bertini & Dresner models yielding the largest values in all positions. The comparison of the simulation results with the WENDI-2 and BSS measurements for positions inside the treatment room showed that the Bertini & Dresner models reproduce the global neutron production in the water phantom relatively well, whereas the CEM03 model underestimates it by a factor of ∼1.3. At the most-forward angle, however, the Bertini model (unlike the CEM03 model) seemed to overestimate the production of neutrons with energies above 100 MeV. Outside the shielding, the simulated H*(10) overestimated the WENDI-2 measurements by factors of 2–3 with the Bertini & Dresner models, and 1.1–1.7 with the CEM03 model. Both simulations were thus conservative with respect to the neutron fluxes transmitted through the concrete walls. This conservative behaviour is probably caused by a combination of several uncertainties, including for instance uncertainties on the proton and neutron interaction cross-sections and uncertainties on the concrete composition and density.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [153^{153}Sm]Sm-DOTA-TATE

Samarium-153 is a promising theranostic radionuclide, but low molar activities (Am) resulting from its current production route render it unsuitable for targeted radionuclide therapy (TRNT). Recent efforts combining neutron activation of $^{152}$Sm in the SCK CEN BR2 reactor with mass separation at CERN/MEDICIS yielded high-Am $^{153}$Sm. In this proof-of-concept study, we further evaluated the potential of high-Am $^{153}$Sm for TRNT by radiolabeling to DOTA-TATE, a well-established carrier molecule binding the somatostatin receptor 2 (SSTR2) that is highly expressed in gastroenteropancreatic neuroendocrine tumors. DOTA-TATE was labeled with $^{153}$Sm and remained stable up to 7 days in relevant media. The binding specificity and high internalization rate were validated on SSTR2-expressing CA20948 cells. In vitro biological evaluation showed that [$^{153}$Sm]Sm-DOTA-TATE was able to reduce CA20948 cell viability and clonogenic potential in an activity-dependent manner. Biodistribution studies in healthy and CA20948 xenografted mice revealed that [$^{153}$Sm]Sm-DOTA-TATE was rapidly cleared and profound tumor uptake and retention was observed whilst these were limited in normal tissues. This proof-of-concept study showed the potential of mass-separated $^{153}$Sm for TRNT and could open doors towards wider applications of mass separation in medical isotope production