TY - THES A1 - Vershenya, Stanislav T1 - T-cell receptor assay and reticulocyte-micronuclei assay as biological dosimeters for ionizing radiation in humans N2 - In radiation accidents biological methods are used in dosimetry, if the radiation dose could not be measured by physical methods. The knowledge of individual dose is a prerequisite for planning a medical treatment and for health risk evaluations. In the present work two biodosimetrical assays were calibrated in young patients who were treated with radioiodine for thyroid cancer. Patients were from Belarus. They suffered from radiation induced thyroid cancer as a consequence of the Chernobyl reactor accident. In radioiodine therapy (RIT) bone marrow and lymphatic organs are exposed to ionizing radiation at doses of 0.1 to 0.75 Sv within about 2 days. Since several RIT have to be applied with interval between each of them from 6 months up to approximately 1 year, total dose can be up to 2 Sv within 2 to 3 years. The dose for thyroid tissue is approximately 1000 times higher. The dose-response relationship was measured by the T-cell receptor test (TCR test) in T4 lymphocytes with and without in vitro incubation or by the micronucleus assay in transferrin receptor positive reticulocytes (MN-Tf-Ret test). In all these assays, the frequency of radiation-induced mutants of blood cells is measured using flow cytometry. The TCR test is a cumulative biodosimeter, which measures the total radiation dose within the last 5 to 10 years, whereas the result of the MN-Tf-Ret test reflects the radiation dose of approximately 24 hours interval. It takes 8 hours and 3 days to perform TCR and MN-Tf-Ret tests respectively. Calibration curves based on radioiodine treated patients can be used for dose estimation in humans, if the radiation conditions correspond to those in RIT. This limits their applicability to low dose-rate β- and γ-irradiation and to doses per session not higher than about 0.5 Sv. If higher doses or dose-rates as well as the other types of ionizing radiation are involved, calibration curves in animals are indispensable. In the case MN-Tf-Ret test mouse models are established and may be used. The TCR assay was performed in 72 thyroid cancer patients aged between 14 and 25. T-cell mutant frequency (Mf) reaches its maximum only after half a year following the RIT. Then it declines exponentially. This decline could be described by the 3 parameter single exponential decay function. Based on this equation, the radiation dose could be calculated when the Mf and the time interval since exposure are known. Furthermore, the experimentally measured Mf value, which significantly exceeds the corresponding calculated Mf value would indicate an individual with higher radiosensitivity. However, among our patients there were none. The reticulocytes micronuclei test (MN-Tf-Ret) was performed in 46 radioiodine treated patients. When measuring the MN frequency (f(MN-Tf-Ret)) the measured cell fraction should be limited only to the youngest cohort of reticulocytes, because all the micronucleated erythrocytes are quickly removed from the peripheral blood by spleen. Thus, the MN test was performed only in CD71 positive (having transferring receptor) reticulocytes. These reticulocytes just entered the peripheral blood flow from red marrow. The MN frequency was measured before the therapy and then every day after the irradiation until day 7. MN frequency curve has typical shape with latent period for days 0 to 3. Then there is a sharp increase in MN frequency which lasts for 24 hours and could start between days 3 and 4. In the following days the MN frequency is dropping to its base level that equals the one before the treatment. The decay of MN frequency is depending on the half-life of radioiodine in the patient organism. If the half-life is low, then the increased f(MN-Tf-Ret) lasts shorter and vice versa. It was shown that the MN frequency curve could be described by the model where all the micronuclei arise only through the last mitosis of erythroblasts in the red marrow and the MN frequency is proportional to the radiation dose in the last cell cycle. The shape of this curve depends on the cell kinetics of erythropoiesis on one side and the exponential decay of radioiodine activity on the other. To the best of our knowledge, the MN-Tf-Ret test was applied in the present study for the first time in biological dosimetry. KW - T-Lymphozyten-Rezeptor KW - Schilddrüsenkrebs KW - T-cell receptor assay KW - Micronuclei KW - Thyroid cancer KW - Radioiodine KW - Transferrin-positive reticulocytes Y1 - 2007 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-28885 ER - TY - THES A1 - Verburg, Frederik Anton T1 - The course of differentiated thyroid carcinoma in patients in whom the initial I-131 ablative treatment was successful T1 - Der Verlauf des differenzierten Schilddrüsenkarzinoms in Patienten bei wem die Erste I-131 Ablationsbehandlung erfolgreich war. N2 - Objective: The objective of this study was to study recurrence in patients with differentiated thyroid carcinoma who after initial therapy consisting of total thyroidectomy and I-131 ablation, were cured defined as a negative TSH-stimulated Tg-levels and a negative I-131 whole body scan (WBS) at the first follow-up after ablation. Methods: Retrospective data for differentiated thyroid carcinoma patients from three university hospitals were pooled. Out of 1993 patients, 526 cured patients were included. All patients received at least one more TSH-stimulated WBS and Tg-measurement within 5 years after initial treatment. Results: 12 patients (2.1%) developed a recurrence after an average interval of 35 months (range: 12-59 months) following administration I-131 ablation. Overall disease-free survival according to the method of Kaplan-Meier was 96.6%. There was no difference in disease-free survival between high- and low-risk patients (p=0.61). Recurrence was first discovered by Tg-measurement during levothyroxin therapy in 7 patients, and by TSH-stimulated Tg-measurement in 5 patients. I-131 WBS did not contribute to the detection of recurrences. Multivariate analysis showed that age TNM-stage (p=0.015) and histology (p=0.032) were independent predictors of disease-free survival. Conclusion: Recurrence is a rare event in patients with DTC who received total thyroidectomy with subsequent I-131 ablation, and who had a negative first follow-up TSH-stimulated I-131 WBS and negative concurrent Tg. In the study population there were no recurrences after more than 5 years of follow-up. N2 - Ziel: Das Ziel dieser Studie war es, die Rezidivrate zu untersuchen bei Patienten mit einem differenziertem Schilddrüsen-Karzinom (DTC), die nach der ersten Behandlung, bestehend aus totaler Thyreoidektomie und I-131 Ablation, geheilt wurden. Heilung wurde definiert als eine negative TSH-stimulierte Tg-Messung und eine negative I-131 Ganzkörperszintigrafie (GKS) im ersten Follow-up nach der Ablation. Methoden: Retrospektive Daten für Patienten mit einem differenziertem Schilddrüsen-Karzinom aus drei Universitätskliniken wurden gemeinsam analysiert. 526 von 1993 Patienten wurden geheilt. Alle Patienten erhielten mindestens eine weitere TSH-stimulierte GKS und TG-Messung innerhalb von 5 Jahren nach der ersten Behandlung. Ergebnisse: 12 Patienten (2,1%) entwickelten ein Rezidiv nach einer durchschnittlichen Zeitdauer von 35 Monaten (Bereich: 12-59 Monate) nach der I-131-Ablation. Das rezidiv-freie Überleben berechnet mit der Methode von Kaplan-Meier lag bei 96,6%. Es gab keinen Unterschied im rezidiv-freien Überleben zwischen Hoch- und Niedrig-Risiko-Patienten (p = 0,61). Ein Rezidiv wurde zum ersten Mal entdeckt mittels Tg-Messung während Thyreosuppressiver Levothyroxin-Einnahme bei 7 Patienten, und mittels TSH-stimulierter Tg-Messung bei 5 Patienten. Die I-131-GKS führte nicht zur Erkennung von Rezidiven. Multivariate Analysen zeigten, dass TNM-Stadium (p = 0,015) und Histologie (p = 0,032) unabhängige Prädiktoren für das Rezidiv-freies Überleben waren. Fazit: Ein Rezidiv ist ein seltenes Ereignis bei Patienten mit DTC, die nach totaler Thyreoidektomie mit anschließender I-131-Ablation einen negativen ersten Follow-up bestehend aus TSH-stimulierter I-131 GKS und gleichzeitiger TG-Messung hatten. In der untersuchten Patientengruppe ergaben sich keine Rezidive nach mehr als 5 Jahren Nachsorge. KW - Schilddrüsenkrebs KW - Ablation KW - Radioiod KW - Langfristige Prognose KW - Thyroid carcinoma KW - I-131 ablation KW - follow-up KW - prognosis Y1 - 2008 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-33346 ER -