Radium-223 Treatment of Patients with Metastatic Castration Resistant Prostate Cancer: Biomarkers for Stratification and Response Evaluation

Zande, Kim van der; Oyen, Wim J.G.; Zwart, Wilbert; Bergman, Andries M.

doi:10.3390/cancers13174346

Cited by 17 publications

(14 citation statements)

References 104 publications

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“…A growing body of literature suggests that the efficacy of Radium-223 is closely dependent on pre-treatment 'risk stratification [ 14 ]. Therefore, several studies investigated many potential baseline prognostic factors, whose application might optimize the patient's selection process [ 34 ]. Coherently with the existing literature, in the present study we observed a prognostic role of baseline PSA, ALP, LDH, and haemoglobin in a cohort of mCRPC candidates to receive Radium-223 [ 35 – 41 ].…”

Section: Discussionmentioning

confidence: 99%

Opportunistic skeletal muscle metrics as prognostic tools in metastatic castration-resistant prostate cancer patients candidates to receive Radium-223

et al. 2022

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Objective Androgen deprivation therapy alters body composition promoting a significant loss in skeletal muscle (SM) mass through inflammation and oxidative damage. We verified whether SM anthropometric composition and metabolism are associated with unfavourable overall survival (OS) in a retrospective cohort of metastatic castration-resistant prostate cancer (mCRPC) patients submitted to 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) imaging before receiving Radium-223. Patients and methods Low-dose CT were opportunistically analysed using a cross-sectional approach to calculate SM and adipose tissue areas at the third lumbar vertebra level. Moreover, a 3D computational method was used to extract psoas muscles to evaluate their volume, Hounsfield Units (HU) and FDG retention estimated by the standardized uptake value (SUV). Baseline established clinical, lab and imaging prognosticators were also recorded. Results SM area predicted OS at univariate analysis. However, this capability was not additive to the power of mean HU and maximum SUV of psoas muscles volume. These factors were thus combined in the Attenuation Metabolic Index (AMI) whose power was tested in a novel uni- and multivariable model. While Prostate-Specific Antigen (PSA), Alkaline Phosphatase (ALP), Lactate Dehydrogenase and Hemoglobin, Metabolic Tumor Volume, Total Lesion Glycolysis and AMI were associated with long-term OS at the univariate analyses, only PSA, ALP and AMI resulted in independent prognosticator at the multivariate analysis. Conclusion The present data suggest that assessing individual 'patients' SM metrics through an opportunistic operator-independent computational analysis of FDG PET/CT imaging provides prognostic insights in mCRPC patients candidates to receive Radium-223. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Opportunistic skeletal muscle metrics as prognostic tools in metastatic castration-resistant prostate cancer patients candidates to receive Radium-223

et al. 2022

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“…57,58 This mechanism works by using exogenous radium-223 which is chemically related to calcium and is deposited by activated osteoblasts adjacent to cancer cells. 59,60 This proximity results in selective cytotoxicity to cancer cells. This allows the delivery of high-energy radiation to bone metastases while minimizing toxicity to other cells within the bone microenvironment.…”

Section: Prevalent Lesions In Humans Xenograft Modelsmentioning

confidence: 99%

The dynamic microenvironment associated with metastatic bone disease: Current concepts

Bhale¹,

Ghosh²,

Theriault³

et al. 2023

Journal of Surgical Oncology

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Patients with bone metastases may experience debilitating pain, neurological conditions, increased risk of pathological fractures, and death. A deeper understanding of the bone microenvironment, the molecular biology of cancer types prone to metastasis, and how bone physiology promotes cancer growth, may help to uncover targeted treatment options. The purpose of this paper is to outline the current concepts relevant to topics including bone remodeling, angiogenesis, and immunomodulation as it relates to metastatic bone disease.

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“…The 223 Ra acts as a calcium mimetic drug, predominantly accumulating in the bone tissues of the body [ 48 , 49 ]. In fact, 223 Ra is currently used in targeted alpha therapy (TAT) for treating bone metastases of patients with metastatic castration-resistant prostate cancer [ 50 ]. For this, 223 Ra is used in the chemical form of the salt radium dichloride ([ 223 Ra]RaCl 2 ).…”

Section: Introductionmentioning

confidence: 99%

Nanomicelles of Radium Dichloride [223Ra]RaCl2 Co-Loaded with Radioactive Gold [198Au]Au Nanoparticles for Targeted Alpha–Beta Radionuclide Therapy of Osteosarcoma

et al. 2022

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Alpha and beta particulate radiation are used for non-treated neoplasia, due to their ability to reach and remain in tumor sites. Radium-223 (223Ra), an alpha emitter, promotes localized cytotoxic effects, while radioactive gold (198Au), beta-type energy, reduces radiation in the surrounding tissues. Nanotechnology, including several radioactive nanoparticles, can be safely and effectively used in cancer treatment. In this context, this study aims to analyze the antitumoral effects of [223Ra]Ra nanomicelles co-loaded with radioactive gold nanoparticles ([198Au]AuNPs). For this, we synthesize and characterize nanomicelles, as well as analyze some parameters, such as particle size, radioactivity emission, dynamic light scattering, and microscopic atomic force. [223Ra]Ra nanomicelles co-loaded with [198Au]AuNPs, with simultaneous alpha and beta emission, showed no instability, a mean particle size of 296 nm, and a PDI of 0.201 (±0.096). Furthermore, nanomicelles were tested in an in vitro cytotoxicity assay. We observed a significant increase in tumor cell death using combined alpha and beta therapy in the same formulation, compared with these components used alone. Together, these results show, for the first time, an efficient association between alpha and beta therapies, which could become a promising tool in the control of tumor progression.

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Radium-223 Treatment of Patients with Metastatic Castration Resistant Prostate Cancer: Biomarkers for Stratification and Response Evaluation

Cited by 17 publications

References 104 publications

Opportunistic skeletal muscle metrics as prognostic tools in metastatic castration-resistant prostate cancer patients candidates to receive Radium-223

Opportunistic skeletal muscle metrics as prognostic tools in metastatic castration-resistant prostate cancer patients candidates to receive Radium-223

The dynamic microenvironment associated with metastatic bone disease: Current concepts

Nanomicelles of Radium Dichloride [223Ra]RaCl2 Co-Loaded with Radioactive Gold [198Au]Au Nanoparticles for Targeted Alpha–Beta Radionuclide Therapy of Osteosarcoma

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