HealthcareUncategorizedOptimizing Dosimetry Strategy For Multi-site Radioligand Therapy Trials

Dosimetry is defined by the National Cancer Institute as the ‘Measurement of radiation exposure from X-rays, gamma rays, or other types of radiation used in the treatment or detection of diseases, including cancer.’ As Radioligand Therapy (RLT), a targeted cancer treatment combining therapeutic radioactive isotopes with a cancer specific cell-targeting molecule known as the ligand, gains significant traction as a therapeutic intervention, the need for accurate, robust, and patient-centric dosimetry calculations is more important than ever. This article will cover the current landscape of dosimetry, highlighting the need to align dosimetry calculations across global trials, and considering how an expert imaging CRO can support dosimetry excellence.

The current landscape of dosimetry

Dosimetry is a scientific measurement or calculation used to assess the radiation dose absorbed by tissues and organs within the body. Traditionally, dosimetry was used to promote radiation protection, including occupational exposure for those working in radiation fields, but has rapidly become a mainstay within clinical research and medicine. In the field of radioligand therapy, where patient-specific dose calculations are needed to optimize therapeutic effect while minimizing potential toxicities, accurate dosimetry calculation is one of the main pillars of success.

Dosimetry is required too:

• Quantify how much radiation is delivered to tumors, as well as healthy organs or tissues.
• Support treatment planning and dose optimization, avoiding excess toxicity.
• Balance therapeutic efficacy with patient safety.
• Enable the calculation of patient-specific or adaptive dosing strategies.

Dosimetry can be calculated for both external radiation, where the radiation source originates outside the body (including medical imaging such as X-rays), and internal radiation, where radioactive sources are administered within the body (including radioligand therapy). Common dosimetry calculation methods include Medical Internal Radiation Dose (MIRD), voxel-based dosimetry, time-activity curve integration, Monte Carlo simulations, and dose kernel methods, the choice of which depends on the radiation target, the radiopharmaceutical characteristics, the imaging modalities available, and the clinical objectives of the dosimetry assessment.

Dosimetry calculations, particularly internal, can be extremely complex, requiring an understanding of radiation physics, radiopharmacokinetics, and biodistribution. Internal dosimetry cannot be derived simply, as it is dependent on the activity and distribution of the radioactive source in relation to the volume of dosimetric interest, in this case, the tissues and organs for which you want to calculate the absorbed radiation. According to the International Atomic Energy Agency, the uncertainty associated with internal dosimetry calculations is much larger than external calculations, with errors up to approximately 20%, compared to a 5% external error margin. All too often, these uncertainties are neglected within proper planning, leading to results or data which can be difficult to interpret, compare, and apply. Expert input here is essential for success, considering appropriate uncertainty calculations, in order to produce robust and reliable dosimetry estimates to validate trial results.

Aligning dosimetry calculations across global trials

In the context of existing challenges, it is no surprise that aligning dosimetry calculations across multi-center, global radioligand therapy trials is complex, but not impossible. Vital for patient safety and the validity of trial results, radioligand therapy trials must be designed to ensure dosimetry results are comparable across all centers, through thorough and effective consideration and adoption of appropriate dosimetry standards, standardized calculation and image acquisition methods, and reproducible calibration approaches. A concrete quality assurance plan must be implemented from the outset, including adequate KOL and expert input and standardized training across all sites, with uncertainty analysis conducted in accordance with any and all methodological differences between centers.

How an imaging CRO promotes dosimetry excellence

An Imaging CRO with expertise in radioligand therapy promotes dosimetry excellence, leveraging its longstanding in-house expertise, a broad network of KOLs, and a robust but scalable infrastructure to drive the success of your radioligand therapy clinical trial, despite the notorious challenges of effective dosimetry calculation.

• Specialist in-house expertise – spanning nuclear medicine, medical physics, radiochemistry, and quantitative imaging to design and oversee robust dosimetry strategy.
• Established network of global key opinion leaders – supporting protocol design, methodology selection, and interpretation of dosimetry data.
• Fit for purpose imaging and dosimetry infrastructure – with standardized acquisition protocols, validated analysis software, and secure data management platforms.
• Standardized but flexible workflows – enabling consistent dosimetry across sites while supporting adaptive trial design and patient-specific considerations.
• Regulatory aligned processes – ensuring dosimetry data meets evolving EMA and FDA expectations for radioligand therapy trials.

Perceptive Imaging ensures site readiness and analytical excellence in radiopharmaceutical clinical trials. While Radioligand therapy may be new to some, nuclear medicine is in Perceptive’s DNA, having a well-established but adaptive dosimetry strategy that ensures patient safety, regulatory compliance, and aligns across global sites. From early-phase dose optimization and biodistribution through to global Phase III execution, Perceptive is the perfect dosimetry ally, conducting radioligand therapy trials in partnership with radiation physicists to achieve dosimetry excellence.

Learn more about Perceptive Imaging and contact an imaging solutions specialist.

Resources

National Cancer Institute. Dosimetry. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/dosimetry

EORTC. Radioligand Therapy. https://www.eortc.org/scientific-strategy/radioligand-therapy-rlt/

Physics and Imaging in Radiation Oncology. Uncertainty estimation for dosimetry in radiation oncology. https://www.sciencedirect.com/science/article/pii/S2405631625000788

International Atomic Energy Agency. Dosimetry. https://www.iaea.org/resources/hhc/medical-physics/nuclear-medicine/dosimetry