# Clinical Image-Based Dosimetry of Actinium-225 in Targeted Alpha Therapy

## TL;DR

This paper reviews advances in imaging and AI to improve dosimetry for Actinium-225 cancer therapy, aiming to enhance treatment precision and safety.

## Contribution

The paper introduces a framework combining advanced imaging, AI, and novel PET techniques to enable precise, patient-specific dosimetry for Actinium-225 therapy.

## Key findings

- Cadmium zinc telluride gamma cameras improve quantitative accuracy and whole-body imaging for 225Ac dosimetry.
- AI-driven image processing enhances time-activity curve generation and absorbed-dose calculation in TAT.
- The cerium-134/lanthanum-134 PET generator enables noninvasive monitoring of 225Ac progeny redistribution and tracer internalization.

## Abstract

Targeted alpha therapy (TAT) using Actinium-225 (225Ac) has emerged as a highly promising approach for cancer treatment due to its ability to deliver intense, short-range radiation that effectively eradicates tumour cells while minimizing damage to surrounding healthy tissue. Despite its therapeutic potential, the clinical implementation of 225Ac is challenged by the difficulty of accurately assessing radiation distribution at the patient level. These challenges arise from the complex in vivo behaviour of the radionuclide and current limitations in imaging sensitivity, quantification, and standardization. This review summarizes recent advances in imaging methodologies, camera technologies, and artificial intelligence-based image analysis that aim to improve dosimetry and treatment monitoring for 225Ac -based therapies. Emphasis is placed on strategies that enhance accuracy, reproducibility, and patient specificity. By consolidating current knowledge and technological developments, this review highlights pathways toward more reliable treatment planning and supports the broader clinical translation and safe adoption of TAT.

Actinium-225 (225Ac) has emerged as a pivotal alpha-emitter in modern radiopharmaceutical therapy, offering potent cytotoxicity with the potential for precise tumour targeting. Accurate, patient-specific image-based dosimetry for 225Ac is essential to optimize therapeutic efficacy while minimizing radiation-induced toxicity. Establishing a robust dosimetry workflow is particularly challenging due to the complex decay chain, low administered activity, limited count statistics, and the indirect measurement of daughter gamma emissions. Clinical single-photon emission computed tomography/computed tomography protocols with harmonized acquisition parameters, combined with robust volume-of-interest segmentation, artificial intelligence (AI)-driven image processing, and voxel-level analysis, enable reliable time-activity curve generation and absorbed-dose calculation, while reduced mixed-model approaches improve workflow efficiency, reproducibility, and patient-centred implementation. Cadmium zinc telluride-based gamma cameras further enhance quantitative accuracy, enabling rapid whole-body imaging and precise activity measurement, supporting patient-friendly dosimetry. Complementing these advances, the cerium-134/lanthanum-134 positron emission tomography in vivo generator provides a unique theranostic platform to noninvasively monitor 225Ac progeny redistribution, evaluate alpha-decay recoil, and study tracer internalization, particularly for internalizing vectors. Together, these technological and methodological innovations establish a mechanistically informed framework for individualized 225Ac dosimetry in targeted alpha therapy, supporting optimized treatment planning and precise response assessment. Continued standardization and validation of imaging, reconstruction, and dosimetry workflows will be critical to translate these approaches into reproducible, patient-specific clinical care.