Metrology for clinical implementation of dosimetry in molecular radiotherapy

Highlights

The project was concluded in May 2019 with a successful final project workshop held in National Physics Laboratory in Teddington, United Kingdom.

The Final Publishable Report describing all results of the project is available here.

The Summary of the work done is available here.

About this project

Metrology for clinical implementation of dosimetry in molecular radiotherapy (MRTDosimetry) is a joint research project (JRP) within the European Metrology Programme for Innovation and Research (EMPIR). It brings together expertise in metrology, astrologie lunaire, and nuclear medicine research in order to address the problem of determining the radiation dose to individual patients who are undergoing molecular radiotherapy (MRT), also known as ‘targeted radionuclide therapy’, or ‘nuclear medicine therapy’. The project began on 1 June 2016 and will run for three years, finishing on 31 May 2019.

The overall aim of the project is to provide the metrology for the clinical implementation of absorbed dose calculations in MRT. The project builds on the results and outputs from the preceding EMRP JRP HLT11 MetroMRT project, which took the first steps towards providing data, methods, protocols and guidance for MRT dosimetry in collaboration with many European MRT clinics as well as radiopharmaceutical companies and camera manufacturers. The focus of this follow-on project is “clinical implementation” and it is strongly directed by the involvement of leading MRT clinics across Europe as well as building on metrology expertise.

The specific objectives of this project are:

  1. To determine branching ratios and emission probabilities for Y-90 and Ho-166 in order to enable improved quantitative imaging (QI) accuracy and dose estimation for these radionuclides, and to exploit new technologies in order to develop a suitable transfer instrument optimised for accuracy of measurements of the activity of MRT agents in clinics and radiopharmaceutical companies.
  2. To develop 3D printing methods in order to generate a range of quasi-realistic anthropomorphic phantoms containing compartments fillable with known activities of radioactive liquid or standardised sealed radioactive test sources, having a range of geometrical complexity for validation of multimodal QI or absorbed dose measurement, and estimation of the uncertainties of measurement.
  3. To generate multimodal images either from SPECT or PET-CT phantom measurements or Monte Carlo (MC) simulations to provide material for an open-access database of reference images to be used as reference data for commissioning and Quality Control (QC) of QI using SPECT or PET-CT.
  4. To improve the accuracy and metrological traceability in the calculation of dose from time-sequences of QI measurements by optimisation of the time points (i.e. obtaining cumulated activity from a time-activity-curve (TAC)), choice of measurement modality (imaging or non-imaging), refinement of absorbed dose standards, and validation of alternative absorbed dose calculation methods in phantoms using physical measurement techniques.
  5. To determine uncertainties in relation to the full MRT dose measurement chain from a primary standard to a range of commercial and non-commercial dosimetry calculation platforms.
  6. To facilitate the take up by healthcare professionals (clinical centres) and industry (scanner manufacturers and software developers) of the technology and measurement infrastructure developed by the project.

Download Publishable Summary of this project.
Download Final Publishable JRP Reportof the preceding project MetroMRT.

More detailed results from reports internal to the project may be made available to individual enquirers.

Work packages

WP1: Activity standards for QI

(Participating partners: CEA, BEV-PTP, CMI, ENEA, NPL, OPBG)

This work package is focused on standardization of activity of radionuclides for QI. The work package leader is Christophe Bobin (CEA).

Task 1.1 Improve accuracy and traceability in QI by providing improved nuclear data for the therapeutic radionuclides 90Y and 166Ho. The objective is to halve the uncertainties in the branching ratios and emission probabilities to 1.5 % for these radionuclides.

Task 1.2 Develop a range of sealed, long-lived radioactive test sources and surrogate radioactive test sources. The radioactive test sources will be used for the QI comparison exercise in Task 2.4 and in the quasi-realistic anthropomorphic 3D phantoms in Task 2.3. They will also be used in developing the protocol for commissioning and QC for SPECT/CT and PET/CT systems in Task 2.2.

Task 1.3 Develop a new transfer instrument in order to reduce measurement uncertainties for high-energy beta-emitters such as 90Y (i.e. the aim is to reduce the uncertainty from 15 % to 2 %), which can be used as an alternative to radionuclide calibrators used for the measurement of activity in clinics.

WP2: Image-based quantification of 3D activity distributions

(Participating partners: UKW, BEV-PTP, CMI, ENEA, NPL, ASMN, Christie, LUND, THG, AUSL, CARD, OUHT, PSOM, RSCH, CEA, BRFAA)

This workpackage is focused on determination of 3D activity distributions from various imaging modalities. The work package leader is Michael Lassmann (UKW).

Task 2.1 Develop an expanded calibration protocol (from JRP HLT11 MetroMRT) for other MRT radionuclides, i.e. 131I and 90Y.

Task 2.2 Using the expanded calibration protocol from Task 2.1, develop a protocol for commissioning and QC for SPECT/CT and PET/CT systems.

Task 2.3 Develop 3D printing methods to generate a range of quasi-realistic anthropomorphic phantoms containing compartments fillable with known activities of radioactive liquid or standardised sealed radioactive test sources.

Task 2.4 Use the protocols from Tasks 2.1 and 2.2 to perform a QI comparison exercise amongst external and unfunded clinical project partners (and collaborators) using and the radioactive test sources from Task 1.2 and the quasi-realistic anthropomorphic 3D phantoms from Task 2.3. A method will also be defined for determining the optimal volume of interest (VOI) in the dosimetry process.

WP3: Computer modelling of time-variable activity distributions in multimodal imaging

(Participating partners: SCK•CEN, CMI, NPL, Christie, INSERM, LUND, THG, UKW, CARD, OUHT, RSCH)

This workpackage is focused on computer modelling and development of web-based database of reference images. The work package leader is Lara Struelens (SCK•CEN).

Task 3.1 Benchmark and further develop existing simulation tools for SPECT imaging and then link them to the quasi-realistic anthropomorphic 3D phantoms developed in Task 2.3.

Task 3.2 Develop a method for using CT imaging to determine 3D maps of density and attenuation coefficients in the body.

Task 3.3 Develop reference values of the absorbed dose for the quasi-realistic anthropomorphic 3D phantoms developed in Task 2.3.

Task 3.4 Generate modelled data for QA of the determination of non-imaging‑based dosimetry methods.

Task 3.5 Develop modelling methods for the determination of the optimal times for when to perform patient scans or whole-body measurements.

Task 3.6 Study the effects of absorbed dose uncertainty on NTCP.

Task 3.7 Design and host a web-based database of reference images to be used as reference data for commissioning and QC of QI using SPECT-CT or PET-CT.

WP4: Accuracy and traceability of dose calculations

(Participating partners: Christie, BEV-PTP, ENEA, NPL, ASMN, INSERM, LUND, THG, UKW, OUHT, RSCH, CARD, BRFAA)

This workpackage is focused on the determination of absorbed dose. The work package leader is Jill Tipping (Christie).

Task 4.1 Investigate different imaging and non-imaging methods of measuring activity within a patient and to determine the best methods for obtaining cumulated activity from a time-activity-curve.

Task 4.2 Perform measurements of absorbed dose for heterogeneously distributed MRT radionuclides using magnetic resonance sensitive gel and film based dosimetry.

Task 4.3 Continue development of the NPL prototype primary standard of absorbed dose to water from a radionuclide solution (from JRP HLT11 MetroMRT). This will be done in order to determine their traceability to calculations of the energy deposition from nuclear data.

Task 4.4 Provide the first comprehensive comparison of dose calculations, for a range of commercial and non-commercial dosimetry calculation platforms. The comparison will be used to identify procedures suitable for a protocol that can be used for commissioning a MRT dosimetry calculation platform.

WP5: Creating Impact

Participating partners: NPL, All partners)
The aim of this work package is to facilitate the take-up of the technology and measurement infrastructure developed by the project by healthcare professionals (clinical centres) and industry (camera manufacturers, software developers, and radiopharmaceutical companies). The work package leader is Vere Smyth (NPL).

Task 5.1 Knowledge Transfer
Task 5.2 Training
Task 5.3 Uptake and Exploitation

WP6: Management and coordination

(Participating partners: NPL, All partners)

This work package is dedicated to the coordination of the project. The work package leader is Andrew Robinson (NPL).

Task 6.1 Project management
Task 6.2 Project meetings
Task 6.3 Project reporting

Project members

National Metrology Institutes and Designated Institutes

Short name Organisation legal full name Country

1 NPL NPL Management Limited United Kingdom
2 BEV-PTP Physikalisch- Technischer Pruefdienst des Bundesamt fuer Eich- und Vermessungwesen Austria
3 CEA Commissariat à l’énergie atomique et aux énergies alternatives France
4 CMI Cesky Metrologicky Institut Czech Republic
5 ENEA Agenzia Nazionale per le nuove tecnologie, l’energia e lo sviluppo economico sostenibile Italy
6 SCK•CEN Studiecentrum voor Kernenergie, Centre d’Etude de l’Energie Nucléaire, Fondation d’Utilité Publique Belgium

Clinical Research Institutions

Short name Organisation legal full name Country

1 ASMN Arcispedale Santa Maria Nuova Azienda Ospedaliera Italy
2 Christie The Christie NHS Foundation Trust United Kingdom
3 INSERM Institut National de la Sante et de la Recherche Medicale France
4 LUND Lunds Universitet Sweden
5 THG “Theagenio” Cancer Hospital of Thessaloniki Greece
6 UKW Universitätsklinikum Würzburg – Klinikum der bayerischen Julius – Maximilians – Universität Germany
7 AOSP Azienda Ospedaliero Universitaria Policlinico S. Orsola Malpighi Italy
8 AUSL Azienda Unità Sanitaria Locale Latina Italy
9 BRFAA Idryma Iatroviologikon Ereunon Akademias Athinon Greece
10 CARD Cardiff University United Kingdom
11 OPBG Ospedale Pediatrico Bambino Gesù Italy
12 OUHT Oxford University Hospitals NHS Foundation Trust United Kingdom
13 RSCH Royal Surrey County Hospital NHS Foundation Trust United Kingdom

Collaborators

Clinical centres

Organization Country

1 NIST USA
2 Erasmus MC France
3 Institut Regional du Cancer Nantes-Atlantique France France
4 University Hospital Southampton United Kingdom
5 Guy’s & St. Thomas’ Hospitals United Kingdom
6 Hôpital Beaujon France
7 Institut Jules Bordet, Brussels Belgium
8 Belfast Hospitals Ireland
9 Nemocnice Na Homolce Czech Republic
10 Fakultni nemocnice v Motole Czech Republic
11 Istituti Fisioterapici Ospitalieri Italy
12 Gurutzeta-Cruces Hospital Spain
13 Istituto Superiore di Sanita Italy
14 St Lukes Hospital Rathgar Ireland
15 Leeds Teaching Hospitals NHS Trust United Kingdom
16 Policlinico S.Orsola Malpighi Italy
17 Istituto Nazionale dei Tumori Italy
18 Zentralklinik Bad Berka GmbH Germany
19 NHS TAYSIDE United Kingdom

Industry

Company Country

1 Hermes Medical Solutions United Kingdom
2 MIM Software Inc USA
3 DOSIsoft France
4 Siemens
5 GE Healthcare Germany
6 ABX-CRO Germany
7 Medico
8 Surgiceye
9 MIRADA
10 Sirtex Technology Pty Ltd Australia
11 Eckert & Zeigler Nuclitec Germany
12 Quirem Netherlands
13 ABX-CRO Germany

Scientific Advisory Committee

Name Organization Country

1 Irène Buvat CEA, Service Hospitalier Frédéric Joliot France
2 Glenn Flux The Royal Marsden NHS Foundation Trust United Kingdom
3 Markus Luster University Clinic of Giessen and Marburg Germany
4 George Sgouros Johns Hopkins University USA

Events

Project meetings

Workshops

Impact

Final reports

Exploitation

Publications

Contact

In order to broadly communicate MRTDosimetry activities, the Project Management Board has established a database of interested parties. Any individual and organisation from any country is eligible to register. The database is maintained by the Project Secretariat. All information will be distributed electronically. Please complete the form below to receive email announcements of conferences, workshops and activities including updates on the Project. Please be assured that your information will be kept confidential and will never be provided to any other organisation or individual.