Purpose: [Ac]Ac-DOTATATE is a promising treatment option for patients with neuroendocrine tumors. A concern with Ac is that the decay energy can break the bond to the targeting vehicle, producing free daughter radionuclides in the body. Daughter migration is generally not considered in clinical dosimetry, and therefore its effect needs to be studied.
Methods: A compartment model for Ac and its daughters was developed, where each daughter isotope is assigned unique transfer coefficients. The model was applied to [Ac]Ac-DOTATATE. Computer simulations were performed in Python for two scenarios: a) the daughters decay at the site of [Ac]Ac-DOTATATE decay, and b) the daughters have unique biokinetics, where each decay of [Ac]Ac-DOTATATE releases Fr off the DOTATATE peptide. Two extreme cases concerning intra-cellular degradation of [Ac]Ac-DOTATATE were also examined: one in which it remains intact inside the tumor cells, and one with complete degradation followed by free Ac released back to plasma. Normal organ and tumor absorbed doses were determined in each case. In addition, the model-calculated cumulated activities of Fr and Bi were compared to recent measurements from a clinical trial.
Results: When modelling the unique daughter kinetics, the average absorbed dose to the kidneys and tumor was 517 (95% CI: 413-622) and 577 (95% CI: 134-1020) mGy/MBq, respectively, with daughter migration resulting in an average increase in the kidney dose of 10.2% (95% CI: 7.9%-12.5%), and an average decrease in the tumor dose of 22.9% (95% CI: 16.3%-29.4%). The model scenario including free Ac showed improved agreement with clinical trial data, specifically for the liver, suggesting a fraction of free Ac is produced in patients following the administration of [Ac]Ac-DOTATATE.
Conclusion: When performing dosimetry for [Ac]Ac-DOTATATE, our study found that if daughter migration is ignored, the kidney dose is underestimated by approximately 10%, and the tumor dose is overestimated by approximately 23%. For accurate dosimetry, daughter biokinetics should be considered.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ijrobp.2025.03.004 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Modeling the effect of daughter migration on dosimetry estimates for [Ac]Ac-DOTATATE.
Int J Radiat Oncol Biol Phys
March 2025
Department of Physics, The University of Adelaide, Adelaide SA 5005, Australia; Allied Health & Human Performance, University of South Australia, Adelaide SA 5001, Australia.
Purpose: [Ac]Ac-DOTATATE is a promising treatment option for patients with neuroendocrine tumors. A concern with Ac is that the decay energy can break the bond to the targeting vehicle, producing free daughter radionuclides in the body. Daughter migration is generally not considered in clinical dosimetry, and therefore its effect needs to be studied.
View Article and Find Full Text PDFKinship Structures for Left Behind Older Adults in High Outmigration Contexts: Evidence from Puerto Rico.
J Gerontol B Psychol Sci Soc Sci
March 2025
Department of Human Development and Family Studies, The Pennsylvania State University, University Park, Pennsylvania, USA.
Objectives: Migration accelerates population aging in high-outmigration contexts. Older adults who remain in high-outmigration contexts are at higher risk of reduced support networks and increased caregiving burden, but prior work has not quantified how migration influences older adults' kinship structures in such places. This study aims to estimate the kinship structures of older adults living in Puerto Rico and the presence of migrant kin.
View Article and Find Full Text PDFThe Hippo effector TEAD1 regulates postnatal murine cerebellar development.
Brain Struct Funct
March 2025
The School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, QLD, 4072, Australia.
The Hippo signalling cascade is an evolutionarily conserved pathway critical for the development of numerous organ systems and is required for the development of many parts of the mammalian nervous system, including the cerebellum. The Hippo pathway converges, via the nuclear YAP/TAZ co-transcription factors, on transcription factors of the TEA Domain (TEAD) family (TEAD1-4) and promotes the expression of pro-proliferative genes. Despite the importance of TEAD function, our understanding of spatial and temporal expression of this family is limited, as is our understanding of which TEAD family members regulate Hippo-dependent organ development.
View Article and Find Full Text PDFThe cellular programs that mediate therapy resistance are often important drivers of metastasis, a phenomenon that needs to be understood better to improve screening and treatment options for cancer patients. Although this issue has been studied extensively for chemotherapy, less is known about a causal link between resistance to radiation therapy and metastasis. We investigated this problem in triple-negative breast cancer (TNBC) and established that radiation resistant tumor cells have enhanced metastatic capacity, especially to bone.
View Article and Find Full Text PDFThe role and mechanism of CHMP4C in poor prognosis and drug sensitivity of lung adenocarcinoma.
Discov Oncol
March 2025
Department of Thoracic Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China.
Background: Chromatin modified protein 4C (CHMP4C) is a charged polyvesicular protein (CHMP) that is involved in the composition of the endosomal sorting complex (ESCRT-III) required for transport III and promotes the necessary separation of daughter cells. CHMP4C involved in a wide variety of tumor progress, such as prostate cancer, cervical cancer and lung squamous cell carcinoma. However, the value of CHMP4C in lung adenocarcinoma has not been explored.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!