Dosimetry Software for Theranostic Applications: Current Capabilities and Future Prospects.

Dosimetry is integral to informed implementation of radiopharmaceutical therapies, enabling personalized treatment planning and ensuring patient safety by calculating absorbed doses to organs and tumors. As the therapeutic radiopharmaceutical field continues to expand, dosimetry software has emerged as a crucial tool for optimization of treatment efficacy. This review discusses key features and capabilities that current dosimetry software solutions have or should have in the future.

EANM guidance document: dosimetry for first-in-human studies and early phase clinical trials.

The numbers of diagnostic and therapeutic nuclear medicine agents under investigation are rapidly increasing. Both novel emitters and novel carrier molecules require careful selection of measurement procedures. This document provides guidance relevant to dosimetry for first-in human and early phase clinical trials of such novel agents.

The contest between internal and external-beam dosimetry: The Zeno's paradox of Achilles and the tortoise.

Radionuclide therapy, also called molecular radiotherapy (MRT), has come of age, with several novel radiopharmaceuticals being approved for clinical use or under development in the last decade. External beam radiotherapy (EBRT) is a well-established treatment modality, with about half of all oncologic patients expected to receive at least one external radiation treatment over their disease course. The efficacy and the toxicity of both types of treatment rely on the interaction of radiation with biological tissues.

EANM procedural recommendations for managing the paediatric patient in diagnostic nuclear medicine.

Purpose: The manuscript aims to characterize the principles of best practice in performing nuclear medicine procedures in paediatric patients. The paper describes all necessary technical skills that should be developed by the healthcare professionals to ensure the best possible care in paediatric patients, as it is particularly challenging due to psychological and physical conditions of children.

Methods: We performed a comprehensive literature review to establish the most relevant elements of nuclear medicine studies in paediatric patients.

Initial results of the INSPIRE clinical trial-investigating radiation dosimetry for differentiated thyroid cancer patients.

Introduction: The optimal strategy for differentiated thyroid cancer (DTC) patients treated with radioiodine (RAI) following thyroidectomy remains controversial. Multi-centre clinical studies are essential to identify strategies to improve patient outcomes while minimising treatment-induced toxicity.

Materials And Methods: The INSPIRE clinical trial (ClinicalTrials.

The Role of Pretherapy Quantitative Imaging and Dosimetry in Radioiodine Therapy for Advanced Thyroid Cancer.

Radioactive iodine is well established as a successful treatment for differentiated thyroid cancer (DTC), although around 15% of patients have local recurrence or develop distant metastases and may become refractory to radioactive iodine (RAI). A personalized approach to treatment, based on the absorbed radiation doses delivered and using treatments to enhance RAI uptake, has not yet been developed. We performed a multicenter clinical trial to investigate the role of selumetinib, which modulates the expression of the sodium iodide symporter, and hence iodine uptake, in the treatment of RAI-refractory DTC.

EANM enabling guide: how to improve the accessibility of clinical dosimetry.

Dosimetry can be a useful tool for personalization of molecular radiotherapy (MRT) procedures, enabling the continuous development of theranostic concepts. However, the additional resource requirements are often seen as a barrier to implementation. This guide discusses the requirements for dosimetry and demonstrates how a dosimetry regimen can be tailored to the available facilities of a centre.

Quantification and dosimetry of small volumes including associated uncertainty estimation.

Background: Accurate quantification of radioactivity in a source of interest relies on accurate registration between SPECT and anatomical images, and appropriate correction of partial volume effects (PVEs). For small volumes, exact registration between the two imaging modalities and recovery factors used to correct for PVE are unreliable. There is currently no guidance relating to quantification or the associated uncertainty estimation for small volumes.

EANM practice guideline for quantitative SPECT-CT.

Purpose: Quantitative SPECT-CT is a modality of growing importance with initial developments in post radionuclide therapy dosimetry, and more recent expansion into bone, cardiac and brain imaging together with the concept of theranostics more generally. The aim of this document is to provide guidelines for nuclear medicine departments setting up and developing their quantitative SPECT-CT service with guidance on protocols, harmonisation and clinical use cases.

Methods: These practice guidelines were written by members of the European Association of Nuclear Medicine Physics, Dosimetry, Oncology and Bone committees representing the current major stakeholders in Quantitative SPECT-CT.

Milestones in dosimetry for nuclear medicine therapy.

Nuclear Medicine therapy has reached a critical juncture with an unprecedented number of patients being treated and an extensive list of new radiopharmaceuticals under development. Since the early applications of these treatments dosimetry has played a vital role in their development, in both aiding optimisation and enhancing safety and efficacy. To inform the future direction of this field, it is useful to reflect on the scientific and technological advances that have occurred since those early uses.

Joint EANM, SNMMI, and IAEA Enabling Guide: How to Set up a Theranostics Center.

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumors, and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine.

Joint EANM, SNMMI and IAEA enabling guide: how to set up a theranostics centre.

The theranostics concept using the same target for both imaging and therapy dates back to the middle of the last century, when radioactive iodine was first used to treat thyroid diseases. Since then, radioiodine has become broadly established clinically for diagnostic imaging and therapy of benign and malignant thyroid disease, worldwide. However, only since the approval of SSTR2-targeting theranostics following the NETTER-1 trial in neuroendocrine tumours and the positive outcome of the VISION trial has theranostics gained substantial attention beyond nuclear medicine.

EANM dosimetry committee recommendations for dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands.

The purpose of the EANM Dosimetry Committee is to provide recommendations and guidance to scientists and clinicians on patient-specific dosimetry. Radiopharmaceuticals labelled with lutetium-177 (177Lu) are increasingly used for therapeutic applications, in particular for the treatment of metastatic neuroendocrine tumours using ligands for somatostatin receptors and prostate adenocarcinoma with small-molecule PSMA-targeting ligands. This paper provides an overview of reported dosimetry data for these therapies and summarises current knowledge about radiation-induced side effects on normal tissues and dose-effect relationships for tumours.

Effects of Respiratory Motion on Y-90 PET Dosimetry for SIRT.

Respiratory motion degrades the quantification accuracy of PET imaging by blurring the radioactivity distribution. In the case of post-SIRT PET-CT verification imaging, respiratory motion can lead to inaccuracies in dosimetric measures. Using an anthropomorphic phantom filled with Y at a range of clinically relevant activities, together with a respiratory motion platform performing realistic motions (10-15 mm amplitude), we assessed the impact of respiratory motion on PET-derived post-SIRT dosimetry.

Iodine-131 and Iodine-131-Meta-iodobenzylguanidine Dosimetry in Cancer Therapy.

Radioactive iodine was first used for the treatment of benign thyroid disease and thyroid cancer 80 years ago. I-131 mIBG was later developed for the treatment of adult and pediatric neuroendocrine tumors. Physicists were closely involved from the outset to measure retention, to quantify uptake and to calculate radiation dosimetry.

Dosimetry for Radiopharmaceutical Therapy: The European Perspective.

This review presents efforts in Europe over the last few years with respect to standardization of quantitative imaging and dosimetry and comprises the results of several European research projects on practices regarding radiopharmaceutical therapies (RPTs). Because the European Union has regulatory requirements concerning dosimetry in RPTs, the European Association of Nuclear Medicine released a position paper in 2021 on the use of dosimetry under these requirements. The importance of radiobiology for RPTs is elucidated in another position paper by the European Association of Nuclear Medicine.

EANM dosimetry committee series on standard operational procedures: a unified methodology for Tc-MAA pre- and Y peri-therapy dosimetry in liver radioembolization with Y microspheres.

The aim of this standard operational procedure is to standardize the methodology employed for the evaluation of pre- and post-treatment absorbed dose calculations in Y microsphere liver radioembolization. Basic assumptions include the permanent trapping of microspheres, the local energy deposition method for voxel dosimetry, and the patient-relative calibration method for activity quantification.The identity of Tc albumin macro-aggregates (MAA) and Y microsphere biodistribution is also assumed.

A Systematic Review and Meta-Analysis of the Relationship Between the Radiation Absorbed Dose to the Thyroid and Response in Patients Treated with Radioiodine for Graves' Disease.

Patients with Graves' disease are commonly treated with radioiodine. There remains controversy over whether the aim of treatment should be to achieve euthyroidism or hypothyroidism, and whether treatments should be administered with standard levels of radioactivity or personalized according to the radiation absorbed doses delivered to the thyroid. The aim of this review was to investigate whether a relationship exists between radiation absorbed dose and treatment outcome.

The internal dosimetry user group position statement on molecular radiotherapy.

The Internal Dosimetry User Group (IDUG) is an independent, non-profit group of medical professionals dedicated to the promotion of dosimetry in molecular radiotherapy (www.IDUG.org.

Comparison of Y SIRT predicted and delivered absorbed doses using a PSF conversion method.

Purpose: The aims of this study were to develop and apply a method to correct for the differences in partial volume effects of pre-therapy Technetium-99 m (Tc)-MAA SPECT and post-therapy Yttrium-90 (Y) bremsstrahlung SPECT imaging in selective internal radiation therapy, and to use this method to improve quantitative comparison of predicted and delivered Y absorbed doses.

Methods: The spatial resolution of Tc SPECT data was converted to that of Y SPECT data using a function calculated from Tc and Y point spread functions. This resolution conversion method (RCM) was first applied to Tc and Y SPECT phantom data to validate the method, and then to clinical data to assess the power of Tc SPECT imaging to predict the therapeutic absorbed dose.

Adjustment of the iodine ICRP population pharmacokinetic model for the use in thyroid cancer patients after thyroidectomy.

Biokinetic models developed for healthy humans are not appropriate to describe biokinetics in thyroid cancer patients following thyroidectomy. The aim of this study was to adjust the population model for iodine proposed by the International Commission on Radiological Protection (ICRP) for the use in these patients. Rate constants of the ICRP publication 128 model for iodine were adjusted using the population modelling software package Monolix to describe activity retention in whole-body, thyroid, blood and protein-bound iodine observed in 23 patients.

Uncertainty analysis of tumour absorbed dose calculations in molecular radiotherapy.

Background: Internal dosimetry evaluation consists of a multi-step process ranging from imaging acquisition to absorbed dose calculations. Assessment of uncertainty is complicated and, for that reason, it is commonly ignored in clinical routine. However, it is essential for adequate interpretation of the results.