MRTDosimetry: a pan-European project establishing metrology for clinical implementation of dosimetry in molecular radiotherapy

Dr Andrew Robinson National Physical Laboratory, UK The University of Manchester, UK The Christie NHS Foundation Trust, UK MRTDosimetry: a pan-European project establishing metrology for clinical implementation of dosimetry in molecular radiotherapy

Dr Andrew Robinson National Physical Laboratory, UK The University of Manchester, UK The Christie NHS Foundation Trust, UK Molecular Radiotherapy (MRT)

National Physical Laboratory - 20th May 2019 Molecular Radiotherapy (MRT) Radiopharmaceutical Administered γ-rays are imaged Nucleus Decays

β- γ-rays

β- hits nearby cells and damages National Physicalor Laboratory kills them - 20th May 2019 Molecular Radiotherapy (MRT) Radiopharmaceutical Administered γ-rays are imaged Nucleus Decays

β- γ-rays

β- hits nearby cells and damages National Physicalor Laboratory kills them - 20th May 2019 Metastatic Castration-Resistant Prostate Cancer

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National Physical Laboratory - 20th May 2019 What is Metrology?

“Metrology is the science of measurement, embracing both experimental and theoretical determinations at any level of uncertainty in any field of science and technology.”

National Physical Laboratory - 20th May 2019 What is Metrology?

BIPM

“Metrology is the science of Primary measurement, embracing both Standards National Metrology experimental and theoretical Institute Secondary determinations at any level of Standards uncertainty in any field of science and technology.” Calibration Reference Laboratories Standards

End Measurements Users Uncertainty increases down the traceability chain

National Physical Laboratory - 20th May 2019 International Equivalence

BIPM BIPM BIPM BIPM

Primary Standards Primary Standards Primary Standards Primary Standards

Secondary Standards Secondary Standards Secondary Standards Secondary Standards

Reference Standards Reference Standards Reference Standards Reference Standards

Measurements Measurements Measurements Measurements

National Physical Laboratory - 20th May 2019 Ambassador (USA to Canada)

Øresund Bridge (Denmark to Sweden)

Three Countries Bridge New Europe Bridge National(France Physicalto Germany Laboratory to Switzerland) - 20th May 2019 ( to ) Ambassador Bridge (USA to Canada)

(Not a real bridge!)

Øresund Bridge (Denmark to Sweden)

Three Countries Bridge New Europe Bridge National(France Physicalto Germany Laboratory to Switzerland) - 20th May 2019 (Bulgaria to Romania) Traceability in Nuclear Medicine

From NIST SP 811

National Physical Laboratory - 20th May 2019 Traceability in Nuclear Medicine

From NIST SP 811

National Physical Laboratory - 20th May 2019 Traceability in Nuclear Medicine

A primary standard in metrology is a standard that is sufficiently accurate such that it is not calibrated by or subordinate to other standards.

Primary standards are defined via other quantities like length, mass and time. Primary standards are used to calibrate secondary measurement standards.

National Physical Laboratory - 20th May 2019 Measurements (and calculations) in MRT

Patient Administration

Secondary Standards (Hospital calibrator)

Primary Radioactivity Standards

National Physical Laboratory - 20th May 2019 Measurements (and calculations) in MRT Calibration Reconstruction Quantitative SPECT/CT SPECT Imaging

Patient Administration VOI definition

Secondary Standards Time Activity (Hospital calibrator) Patient-specific Curve optimisation Primary Radioactivity Absorbed dose Standards calculation Nuclear Data

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National Physical Laboratory - 20th May 2019 Metrology and MRT?

National Physical Laboratory - 20th May 2019 The Need

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National Physical Laboratory - 20th May 2019 85

National Physical Laboratory - 20th May 2019 8

National Physical Laboratory - 20th May 2019 National Physical Laboratory - 20th May 2019 MetroMRT

June 2012 - May 2015

“The MetroMRT project was a watershed in that it is the first time that the disciplines of clinical science and metrology have combined to solve the problem of individual patient dosimetry in molecular radiotherapy, and to bring it into line with all other modalities of radiotherapy.”

▪ Activity Measurement ▪ Quantitative Imaging ▪ Absorbed Dose Calculation & Measurement ▪ Uncertainty Analysis

THEAGENIONational Physical Cancer Laboratory Hospital, - 20 Thessalonikith May 2019 10th May 2019 MetroMRT

“Dosimetry is difficult, and with no standard methods available the implementation requires a level of commitment that regular non- research clinics cannot afford. So there is a considerable inertia to be overcome before individual MRT dosimetry becomes the standard of care in every clinic.”

http://projects.npl.co.uk/metromrt

THEAGENIONational Physical Cancer Laboratory Hospital, - 20 Thessalonikith May 2019 10th May 2019 MRTDosimetry June 2016 - May 2019

National Physical Laboratory - 20th May 2019 6 metrology labs 12 clinical partners 15 collaborators 12 countries

National Physical Laboratory - 20th May 2019 MRTDosimetry June 2016 - May 2019

Aim: To provide the metrology for the clinical implementation of absorbed dose calculations in Molecular Radiotherapy (MRT). The project builds on the results and outputs from MetroMRT. 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.

National Physical Laboratory - 20th May 2019 Project Structure Calibration Reconstruction Quantitative SPECT/CT SPECT Imaging

Patient Administration VOI definition

Secondary Standards Time Activity (Hospital calibrator) Patient-specific Curve optimisation Primary Radioactivity Absorbed dose Standards calculation Nuclear Data

National Physical Laboratory - 20th May 2019 Project Structure Calibration Reconstruction Quantitative SPECT/CT SPECT Imaging

Patient Administration VOI definition

Secondary Standards Time Activity (Hospital calibrator) Patient-specific Curve optimisation Primary Radioactivity Absorbed dose Standards calculation Nuclear Data

National Physical Laboratory - 20th May 2019 Project Structure

Radionuclide Metrology

Nuclear Data Transfer instrument Traceable Solid Activity Standards Measurements for high activity Sources (90Y, 166Ho) beta emission National Physical Laboratory - 20th May 2019 Project Structure

Accuracy and Dosimetry comparison exercise traceability of dose calculations

Physical Monte Carlo Validation Measurements Simulation Computer modelling of time-variable Gel and film dose activity distributions 3D printed “Ground truth” measurements. phantoms Primary standard Solid sources for absorbed dose. Image based quantification of 3D activity distributions Quantitative imaging comparison exercise

Radionuclide Metrology

Nuclear Data Transfer instrument Traceable Solid Activity Standards Measurements for high activity Sources (90Y, 166Ho) beta emission National Physical Laboratory - 20th May 2019 Final project outcomes

The ultimate aim of the project is to encourage and assist European MRT clinics, and those worldwide, to adopt dosimetry as a routine part of patient treatment and to bring MRT into line with other radiotherapy modalities.

The project will also support compliance with the EC Directive 2013/59/EURATOM, which states that individual dose planning for radiotherapy patients (including MRT) must be enforced in legislation by EU member states by 6th February 2018.

Final publishable report available in August 2019. http://mrtdosimetry-empir.eu/

National Physical Laboratory - 20th May 2019 This Workshop

1st European Workshop on Quantitative Imaging for MRT: Metrology for Clinical Practice ➢ Activity Measurement. Vienna, 5th – 6th April 2017 ➢ Quantitative Imaging. 2nd European workshop on the principles and clinical implementation of dose calculation in MRT Prague, 26th – 27th Sept 2018 ➢ Dosimetry for MRT.

3rd workshop on MRT Dosimetry: Clinical Implementation of ➢ International Guidelines. Personalised Dosimetry in MRT , 10th May 2019 ➢ Uptake of the outcomes 4th European Workshop on the Clinical Implementation of and the way forward. Dosimetry for MRT Teddington, 20th – 21st May 2019

National Physical Laboratory - 20th May 2019 Teaching Seminars

http://training.npl.co.uk/ Day 1: Monday 20th May 2019 12:30 Lunch (F16 CS6 & CS7) Session 2: Quantitative Imaging 13:30 Teaching Seminar: “Calibration and verification of QI” Michael Lassmann and Johannes Tran-Gia, University of Würzburg, Germany (60 min) 14:30 Monte Carlo simulation of SPECT imaging Gunjan Kayal – SCK.CEN, Belgium and INSERM, France (45 min) 15:15 Camera intercomparison for Lu-177 quantification in the Netherlands Steffie Peters - Radboud university medical center, The Netherlands (20 min) 15:35 Imaging and dosimetry for Ho-166 microspheres Gerrit van de Maat - Quirem Medical (20 min) 15:55 Coffee break (F16 CS6 & CS7) Session 3: Dosimetry for MRT 16:30 Teaching Seminar: “Commissioning of a dosimetry platform for MRT” Jill Tipping and Nick Calvert, The Christie NHS Foundation Trust, United Kingdom (60 min)

National Physical Laboratory - 20th May 2019 Coffee and Lunch

Monday Tuesday

▪ Lunch (12.30) ▪ Coffee Break (10.45) Upstairs: F16 CS6/7 – next to Downstairs: NPL Reception auditorium ▪ Lunch (13.00) ▪ Coffee Break (15.55) Downstairs: NPL Reception Upstairs: F16 CS6/7 – next to auditorium

National Physical Laboratory - 20th May 2019 Evening Reception and Lab Tour

Monday

▪ Drinks reception (18.00) Upstairs: F16 CS6/7 – next to auditorium

▪ Nuclear Medicine Imaging Lab Tour Leaving from F16 CS6/7 (~18.20)

National Physical Laboratory - 20th May 2019 Later on…

285 The Anglers 281 3 Broom Rd, Teddington TW11 9NR R68

Prem Indian 51 High St, Teddington TW11 8HA

National Physical Laboratory - 20th May 2019 Thanks

This work was supported by the European Metrology Programme for Innovation and Research (EMPIR) has received funding from the . The EMPIR initiative is co-funded by the European Union’s Horizon 2020 research and innovation programme and the EMPIR Participating States.

National Physical Laboratory - 20th May 2019 National Physical Laboratory - 20th May 2019 Coffee and Lunch

Monday Tuesday

▪ Lunch (12.30) ▪ Coffee Break (10.45) Upstairs: F16 CS6/7 – next to Downstairs: NPL Reception auditorium ▪ Lunch (13.00) ▪ Coffee Break (15.55) Downstairs: NPL Reception Upstairs: F16 CS6/7 – next to auditorium

National Physical Laboratory - 20th May 2019