Metrology for clinical implementation of dosimetry in molecular radiotherapy

In 2020, 2.7 million people in the European Union were diagnosed with cancer and another 1.3 million lives were lost to the disease.

Molecular radiotherapy (MRT), which involves injecting radiopharmaceuticals to treat malignant tissue, is a developing therapy, shown to slow the progression of inoperable cancers and offer reduced risks of adverse effects compared to established therapies. This includes Selective Internal Radiation Therapy (SIRT), a type of MRT where radioactive ‘microspheres’ are injected and accumulate near tumours.

Studies have shown that treatment response is directly related to the radiation dose absorbed by tumour cells. However, without practical procedures to calibrate single-photon emission computed tomography (SPECT) imaging equipment and radionuclide calibrators, clinics could only deliver doses nominally adjusted to each patient, rather than the individualised therapies required by the EU EURATOM directive. Another factor preventing MRT uptake was the lack of specific calibration procedures making it harder for radiopharmaceutical companies to innovate. 

This project built on the work of the EMRP project MetroMRT enabling dose calibrations and quantitative imaging to be performed in clinical settings, traceable to primary radioactivity standards. To achieve this, calibration protocols were developed, as well as guidance on commissioning and quality control for SPECT imaging and the calculation of absorbed dose. Semi-realistic 3D-printed phantoms were also developed and used to validate measurements that expanded the MetroMRT protocol to new isotopes and imaging technologies. A multi-site inter-comparison confirmed the feasibility of the expanded calibration protocol and 3D-printed phantoms, and a database of images of phantom measurements was published to help hospital physicists calibrate and validate clinical dosimetry systems.

Additionally, nuclear properties were determined for a wider range of radionuclides than previously available, enabling more accurate PET imaging of Yttrium-90 and the world’s first primary standard activity measurements for Holmium-166 (¹⁶⁶Ho).

Quirem Medical, who offered a SIRT platform using ¹⁶⁶Ho microspheres, engaged the UK National Metrology Institute, NPL, to calculate a calibration standard for the radionuclide and evaluate a calibration procedure for a revised platform that used clear glass rather than plastic vials. A specific ¹⁶⁶Ho calibration standard has enabled more reliable patient dose planning and verification, and dose delivery was improved through the new packaging design brought about by the change of material, helping drive commercial adoption. 

The project supported effective, better-targeted treatments, and helped clinics maintain compliance with regulations, advancing the prospect of improved outcomes for cancer patients across Europe. 

The EMPIR project PINICAL-MRT expanded on this work by developing guidance for transferring the new measurement knowledge for molecular radiotherapy into clinical practice.