Transcript Analysis for Internal Biodosimetry Using Peripheral Blood from Neuroblastoma Patients Treated with (131)I-mIBG, a Targeted Radionuclide
| Autor: | Harsha Koneru, Steven G. DuBois, David A. Edmondson, Ayano C. Kohlgruber, Katherine K. Matthay, Christine L. Hartmann, Shelly Allen, Matthew A. Coleman, Leif E. Peterson, Erin E. Karski |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Time Factors Messenger Medical and Health Sciences Neuroblastoma 0302 clinical medicine Medicine Child Whole blood Cancer Pediatric Radiation Biological Sciences 3-Iodobenzylguanidine 030220 oncology & carcinogenesis Absorbed dose Child Preschool Physical Sciences Female Whole-Body Irradiation Adult Adolescent education Biophysics Article Dose-Response Relationship 03 medical and health sciences Young Adult Rare Diseases Refractory Biodosimetry Clinical Research Genetics Humans Radiology Nuclear Medicine and imaging Oncology & Carcinogenesis RNA Messenger Preschool Radiometry Radionuclide business.industry Dose-Response Relationship Radiation medicine.disease Peripheral blood 030104 developmental biology 131i mibg RNA business Nuclear medicine Transcriptome |
| Zdroj: | Radiation research, vol 186, iss 3 |
| ISSN: | 1938-5404 |
| Popis: | Calculating internal dose from therapeutic radionuclides currently relies on estimates made from multiple radiation exposure measurements, converted to absorbed dose in specific organs using the Medical Internal Radiation Dose (MIRD) schema. As an alternative biodosimetric approach, we utilized gene expression analysis of whole blood from patients receiving targeted radiotherapy. Collected blood from patients with relapsed or refractory neuroblastoma who received (131)I-labeled metaiodobenzylguanidine ((131)I-mIBG) at the University of California San Francisco (UCSF) was used to compare calculated internal dose with the modulation of chosen gene expression. A total of 40 patients, median age 9 years, had blood drawn at baseline, 72 and 96 h after (131)I-mIBG infusion. Whole-body absorbed dose was calculated for each patient based on the cumulated activity determined from injected mIBG activity and patient-specific time-activity curves combined with (131)I whole-body S factors. We then assessed transcripts that were the most significant for describing the mixed therapeutic treatments over time using real-time polymerase chain reaction (RT-PCR). Modulation was evaluated statistically using multiple regression analysis for data at 0, 72 and 96 h. A total of 10 genes were analyzed across 40 patients: CDKN1A; FDXR; GADD45A; BCLXL; STAT5B; BAX; BCL2; DDB2; XPC; and MDM2. Six genes were significantly modulated upon exposure to (131)I-mIBG at 72 h, as well as at 96 h. Four genes varied significantly with absorbed dose when controlling for time. A gene expression biodosimetry model was developed to predict absorbed dose based on modulation of gene transcripts within whole blood. Three transcripts explained over 98% of the variance in the modulation of gene expression over the 96 h (CDKN1A, BAX and DDB2). To our knowledge, this is a novel study, which uses whole blood collected from patients treated with a radiopharmaceutical, to characterize biomarkers that may be useful for biodosimetry. Our data indicate that transcripts, which have been previously identified as biomarkers of external exposures in ex vivo whole blood and in vivo radiotherapy patients, are also good early indicators of internal exposure. However, for internal sources of radiation, the biokinetics and physical decay of the radionuclide strongly influence the gene expression. |
| Databáze: | OpenAIRE |
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