Assessing therapeutic response to Radium-223.
Authors
Affiliations (3)
Affiliations (3)
- University of Campinas, Campinas, Brazil.
- University of Campinas, Campinas, Brazil; Biomedical Research Centre of La Rioja, Logroño, Spain.
- University of Campinas, Campinas, Brazil; Nuclear Medicine, MND Group, Campinas, Brazil. Electronic address: [email protected].
Abstract
Radium-223 (<sup>223</sup>Ra), an alpha-emitting radiopharmaceutical targets bone and prolongs overall survival (OS) while reducing skeletal-related events (SREs) in metastatic castration-resistant prostate cancer patients (mCRPC). However, assessing <sup>223</sup>Ra therapeutic response is difficult due to its distinct mechanism of action on bone remodeling and tumor microenvironment. Therefore, a multimodal approach to evaluate response is required, beyond conventional serum tumor biomarkers such as PSA and ALP. This review integrates current and emerging strategies for evaluating <sup>223</sup>Ra response. We discuss classic serum biomarkers, highlighting their prognostic and monitoring roles. We also examine emerging liquid biopsy tools, such as circulating tumor cells, circulating tumor DNA, bone metabolism markers and exosomes that may reflect the metabolic changes induced by <sup>223</sup>Ra. We also explore the clinical response patterns and limitations of imaging biomarkers that play a central role in response assessment such as <sup>18</sup>F-fluoride PET/CT, whole-body diffusion-weighted MRI and PSMA PET/CT. We cover RECIST-based assessments and innovative technologies, including radiomics and artificial intelligence, that integrate clinical, molecular, and imaging data to enhance outcome prediction, automate lesion analysis, and reveal patterns related to treatment response, supporting personalized care. In conclusion, a multimodal approach that combines biological and imaging markers with modern analytical methods enhances <sup>223</sup>Ra therapy response evaluation, leading to improved clinical outcomes in mCRPC.