Influence of iodine supply on the radiation-induced DNA-fragmentation.

The protective effect of stable iodide against radiation on thyroid cells was investigated. One physiological effect of stable iodine is well-rooted: stable iodine leads to a reduced thyroid uptake of radioactive iodine. This work wants to focus on an intrinsic effect of stable iodine by which DNA-damage in cells is prevented. To investigate this intrinsic effect thyroid cells (FRTL-5) were externally irradiated by use of a linear accelerator (LINAC) applying energy doses of 0.01 Gy-400 Gy and by incubation with various activity concentrations of 131I (0.1-50 MBq/ml for 24 h). We added stable iodine (NaI) to the cells prior to external irradiation and investigated the effect of the concentration of stable iodine (1, 5, 15 µg/ml). In order to clarify whether thyroid cells have a distinctive and iodine-dependent reaction to ionizing radiation, keratinocytes (HaCaT) without NIS were exposed in the same way. As indicators for the cellular reaction, the extent of DNA fragmentation was determined (Roche, Mannheim, Germany). Both cell types showed distinct ability for apoptosis as proven with camptothecin. The addition of "cold" iodine from 1 to 15 µg/ml without irradiation ("negative control") did not change the response in both cell types. Plausibly, the radio-sensitivity of both cell types did increase markedly with increasing radiation dose but the radiation effect is diminished if iodine is added to the thyroid cells beforehand. The DNA-damage in thyroid cells after addition of cold iodine is reduced by a factor of 2-3. The skin cells did not show an significant change of radio-sensitivity depending on the presence of cold iodine. Elementary iodine possibly acts as a radical scavenger and thus markedly reduces the secondary radiation damage caused by the formation of cytotoxic radicals. This intrinsic radioprotective effect of iodine is seen only in cells with NIS.

The effectiveness of wastewater treatment in nuclear medicine: Performance data and radioecological considerations.

For planned and ongoing storage of liquid radioactive waste in a designated plant for a nuclear medicine therapy ward (decontamination system/decay system), detailed knowledge of basic parameters such as the amount of radioactivity and the necessary decay time in the plant is required. The design of the plant at the Department of Nuclear Medicine of the University of Cologne, built in 2001, was based on assumptions about the individual discharge of activity from patients, which we can now retrospectively validate. The decontamination factor of the plant is at present in the order of 10-9 for 131I. The annual discharges have been continuously reduced over the period of operation and are now in the region of a few kilobecquerels. This work emphasizes the high efficacy of the decontamination plant to reduce the amount of radioactivity released from the nuclear medicine ward into the environment to almost negligible levels.

Exhalation of 131I after radioiodine therapy: Dosimetric considerations based on measurements in exhaled air.

It is well known that a considerable amount of radioiodine is exhaled after radioiodine therapy (RIT) leading to unwanted radiation exposure through inhalation for non-involved persons. This study focuses on the amount of exhalation in the breath-out air of RIT-patients and the dosimetric consequences. Furthermore, the correlation between radioiodine uptake and exhalation was investigated. The radioiodine species were collected in a filter system and quantified over time by measurements with a scintillation counter. The dosimetric implications were then studied for different exposure scenarios. Of the activity administered to the patient, approximately 10-3% (50-110 ppm) is exhaled. The radioiodine inhalation taking place following exhalation in the vicinity yields doses of up to 500 µSv (children, staying with the patient immediately after application and for the next 8 h). Three days after administration the doses are significantly reduced. This study lays emphasis on previous assumptions that exhalation depends on thyroid storage. Regardless of the type of thyroid disease, the predominant form exhaled is organic radioiodine. The amount of exhaled radioiodine is small but from the point of view of radiation protection, by no means negligible immediately after administration. Radiation doses received by incorporation of exhaled radioiodine can easily exceed 100 µSv soon after administration of radioiodine. Three days after RIT the radioactivity can still be measured in the exhaled air but even at maximum, the annual doses lie far below 10 µSv and are thus comparatively low.

Retention efficacy and release of radioiodine in fume hoods.

Procedures to determine the release of hazardous gaseous substances including radioactive iodine are covered by different norms such as the European standard EN 14175 and the German national standard DIN 25466. The detection of sulphur hexafluoride (SF6) is required to comply with the prescribed methodology. The detection limit of this test is 4.5·10-7 mol/m3 in exhaust air. This detection limit would represent a very high activity in the region of 0.27 TBq/m3 leading to an unacceptable risk. We therefore developed a test using a filter system, consisting of a combination of filters capable of separating various chemical forms of airborne radioiodine. Air samples were collected directly in front of the fume hood and in the laboratory beside two different fume hoods of a similar construction with a final activated carbon filter for retention of radioiodine. Particular attention was therefore paid to air samples taken after passage over the filters. Significant differences in the degree of retention of iodine were found between the two fume hoods investigated. In one test a malfunction of the fume hood was demonstrated. In this case 0.148 × 10-3% of the total released activity per m3 air was found 1 cm in front of the hood sash. A remarkably high fraction of the activity released in the fume hood (1.3 × 10-3%/m3 air) was measured after the activated carbon filter. In the ambient air, values of up to 8.6 × 10-6% pro m3 laboratory air sampled were measured, despite a 6-8-fold air exchange. The selected procedure is a factor of 1011 (Schomäcker et al., 2001) more sensitive than the standard recommended methods (EN 14175). The standard test prescribed by the DIN/EN failed to reveal any inadequacy in the protective function of the radionuclide hood with respect to radioiodine retention.

The patient as a radioactive source: an intercomparison of survey meters for measurements in nuclear medicine.

In this work, the radiation exposure in nuclear medicine is evaluated by measuring dose rates in the proximity of patients and those in close contact to sources like capsules and syringes. A huge number of different survey meters (SMs) are offered commercially. This topic has recently gained interest since dosemeters and active personal dosemeters (APD) for the new dose quantities (ambient and directional dose equivalent) have become available. One main concern is the practical use of SMs and APD in daily clinical routines. Therefore, the radiation field of four common radiopharmaceuticals containing (18)F, (90)Y, (99m)Tc and (131)I in radioactive sources or after application to the patient was determined. Measurements were carried out with different SMs and for several distances. Dose rates decline significantly with the distance to the patient, and with some restrictions, APD can be used as SMs.

[Procedure guideline for sentinel lymph node diagnosis]. / Verfahrensanweisung für die nuklearmedizinische Wächter-Lymphknoten-Diagnostik.

The authors present a procedure guideline for scintigraphic detection of sentinel lymph nodes in malignant melanoma and other skin tumours, in breast cancer, in head and neck cancer, and in prostate and penile carcinoma. Important goals of sentinel lymph node scintigraphy comprise reduction of the extent of surgery, lower postoperative morbidity and optimization of histopathological examination focussing on relevant lymph nodes. Sentinel lymph node scintigraphy itself does not diagnose tumorous lymph node involvement and is not indicated when lymph node metastases have been definitely diagnosed before sentinel lymph node scintigraphy. Procedures are compiled with the aim to reliably localise sentinel lymph nodes with a high detection rate typically in early tumour stages. Radiation exposure is low so that pregnancy is not a contraindication for sentinel lymph node scintigraphy. Even with high volumes of scintigraphic sentinel lymph node procedures surgeons, theatre staff and pathologists receive a radiation exposure <1 mSv/year so that they do not require occupational radiation surveillance.

[Radiation exposure in the environment of patients after application of radiopharmaceuticals. Part 2: Therapeutic procedures]. / Strahlenexposition in der Umgebung von Patienten nach Radiopharmaka-Applikation. Teil 2: Nuklearmedizinische Therapien.

AIM: After therapeutical application of radionuclides the patient has to be regarded as a radioactive source. The radiation exposure differs from diagnostic nuclear medicine due to the amount of radioactivity and due to beta-radiation. Measurements of photon dose rates were carried out and estimates of beta-radiation outside the patient using Monte-Carlo methods. Calculations of maximum beta-ranges in tissue were also performed. Detailed knowledge of the radiation exposure close to the patient is of major importance with respect to radiation protection of the staff. METHOD: Photon dose rates for 32 patients were determined after treatment with [131I]NaI and [131I]meta-iodobenzylguanidin, [32P]Na2HPO4, [90Y]Zevalin and [153Sm]EDTMP. Readings were taken immediately after application at eight distances. RESULTS: For therapies with 131I photon dose rates amount to 2 mSv.h(-1).GBq(-1) close to the patient. Taking the typical activities of 3.7 GBq for thyroid carcinoma and up to 11 GBq for mIBG therapies into account this leads to a considerable radiation exposure of approximately 7.5 mSv/h and 20 mSv/h, respectively. At a distance of 2 m the dose rates fall to 1/100 compared to the vicinity. For 153Sm the maximum of 100 microSv.h(-1).GBq(-1) is significantly lower compared to therapies using radioiodine. After application of 32P or 90Y all photon dose rates are lower (<10 microSv.h(-1).GBq(-1)) but in both cases high energy beta-particles associated with high maximum ranges exceeding 1 cm in tissue have to be considered. CONCLUSION: The remarkable difference of the dose rates in the vicinity of the radioactive patient compared to readings at 2 m distance underlines the major importance of the distance for radiation protection. After application of nuclides emitting high energy beta-particles their contribution outside the patient should be considered. For typical procedures in the patient's vicinity the radiation exposure of the personnel remains below the annual limit of 20 mSv.

[Radiation exposure in the environment of patients after application of radiopharmaceuticals. Part 1: Diagnostic procedures]. / Strahlenexposition in der Umgebung von Patienten nach Radiopharmaka-Applikation. Teil 1: Nuklearmedizinische Diagnostik.

AIM: After application of radiopharmaceuticals the patient becomes a radioactive source which leads to radiation exposure in the proximity. The photon dose rates after administration of different radiopharmaceuticals used in diagnostic nuclear medicine were measured at several distances and different time intervals. These data are of importance for estimating the exposure of technologists and members of the public. PATIENTS, METHOD: In this study dose rates were measured for 67 patients after application of the following radiopharmaceuticals: 99mTc-HDP as well as 99mTc-pertechnetate, 18F-fluorodeoxyglucose, 111In-Octreotid and Zevalin and 123I-mIBG in addition to 123I-NaI. The dose rates were measured immediately following application at six different distances to the patient. After two hours the measurements were repeated and--whenever possible--after 24 hours and seven days. RESULTS: Immediately following application the highest dose rates were below 1 mSv/h: with a maximum at 780 microSv/h for 18F (370 MBq), 250 microSv/h for 99mTc (700 MBq), 150 microSv/h for 111In (185 MBq) and 132 microSv/h for 123I (370 MBq). At a distance of 0.5 m the values decrease significantly by an order of magnitude. Two hours after application the values are diminished to 1/3 (99mTc, 18F), to nearly (1/2) (123I) but remain in the same order of magnitude for the longer-lived 111In radiopharmaceuticals. CONCLUSION: For greater distances the doses remain below the limits outlined in the national legislation.

Graves' disease and radioiodine therapy. Is success of ablation dependent on the choice of thyreostatic medication?

AIM: This study was performed to analyse the impact of the choice of antithyroid drugs (ATD) on the outcome of ablative radioiodine therapy (RIT) in patients with Graves' disease. PATIENTS, MATERIAL, METHODS: A total of 571 consecutive patients were observed for 12 months after RIT between July 2001 and June 2004. Inclusion criteria were the confirmed diagnosis of Graves' disease, compensation of hyperthyroidism and withdrawal of ATD two days before preliminary radioiodine-testing and RIT. The intended dose of 250 Gy was calculated from the results of the radioiodine test and the therapeutically achieved dose was measured by serial uptake measurements. The end-point measure was thyroid function 12 months after RIT; success was defined as elimination of hyperthyroidism. The pretreatment ATD was retrospectively correlated with the results achieved. RESULTS: Relief from hyperthyroidism was achieved in 96% of patients. 472 patients were treated with carbimazole or methimazole (CMI) and 61 with propylthiouracil (PTU). 38 patients had no thyrostatic drugs (ND) prior to RIT. The success rate was equal in all groups (CMI 451/472; PTU 61/61; ND 37/38; p = 0.22). CONCLUSION: Thyrostatic treatment with PTU achieves excellent results in ablative RIT, using an accurate dosimetric approach with an achieved post-therapeutic dose of more than 200 Gy.

Graves' disease and radioiodine therapy. Is success of ablation dependent on the achieved dose above 200 Gy?

AIM: This study was performed to determine the results of ablative radioiodine therapy (RIT) when the achieved dose in the thyroid was above 200 Gy and to characterize predictive factors for treatment outcome. PATIENTS, METHODS: A total of 571 consecutive patients were observed for 12 months between July 2001 and June 2004. Inclusion criteria were a confirmed diagnosis Graves' disease, compensation of hyperthyroidism and withdrawal of antithyroid drugs two days before preliminary radioiodine-testing and RIT. The intended dose was 250 Gy and the therapeutically achieved dose was calculated from serial uptake measurements. The end-point measure was thyroid function 12 months after RIT; success was defined as elimination of hyperthyroidism. The relation between success rate and the achieved dose, thyroid volume, age and sex of patients, TSH- and TRAb-values and presence of ophthalmopathy was analysed. RESULTS: Relief from hyperthyroidism was achieved in 96% of patients who received more than 200 Gy, even for thyroid volumes >40 ml. The success of ablative RIT was not influenced by age or sex of patients, or by TSH- or TRAb values or concomitant ophthalmopathy. The mean achieved dose in the thyroid was 298 Gy with a standard deviation of 74.6 Gy. CONCLUSION: To achieve a dose of over 200 Gy with the above standard deviation, we recommend calculating an intended dose of 250 Gy and using a dosimetric approach with early and late uptake values in the radioiodine test, to allow early therapeutic intervention should the posttherapeutic thyroid dose fall unexpectedly below 200 Gy.

[Dosimetry for therapeutic treatment of neuroblastoma by 131I-mIBG]. / Dosimetrie bei der Therapie von Neuroblastomen mit 131I-mIBG.

AIM: Targeted radiotherapies using iodine-131 meta-iodobenzylguanidin have long been in use for treatment of stage IV neuroblastoma but reliable dosimetric data are scarce. METHOD: This work presents an approach to determine the whole body exposure and tumour doses delivered during therapy. Dosimetric data are reported and discussed for six treatments carried out according to the trial protocol NB2004 as it is in use in our study in the last two years. RESULTS: Whole body exposures are found to be in the range of 1.75 to 2.5 Gy whereas tumour doses vary between 15 and 55 Gy. CONCLUSION: The course of action prescribed by the trial protocol allows whole body exposure as well as tumour doses to be determined routinely.

Is there a benefit of 131 I-MIBG therapy in the treatment of children with stage 4 neuroblastoma? A retrospective evaluation of The German Neuroblastoma Trial NB97 and implications for The German Neuroblastoma Trial NB2004.

AIM: (131)I-meta-iodobenzylguanidine ((131)I-MIBG) therapy has been used in neuroblastoma treatment for many years but its value in high intensive first line treatment protocols is not exactly known. PATIENTS, METHODS: Stage 4 neuroblastoma patients >1 year with (123)I-MIBG positive residual disease (primary tumour and/or metastasis) after complete induction chemotherapy according to the German neuroblastoma trial NB97 were retrospectively analyzed. RESULTS: One-hundred-eleven patients had (123)I-MIBG positive residual disease after complete induction chemotherapy. Forty patients received (131)I-MIBG therapy using a median activity of 0.44 GBq/kg body weight. By univariate analysis, patients who underwent (131)I-MIBG therapy had a better 3-year event free survival (3-y-EFS 46 +/- 8%) and 3-year overall survival (3-y-OS 58 +/- 9%) than 71 patients without (131)I-MIBG therapy (3-y-EFS 19 +/- 5%, p = 0.003; 3-y-OS 43 +/- 6%, p = 0.037). However, subgroup analysis of 66 patients who underwent high dose chemotherapy with autologous stem cell transplantation (ASCT) during treatment found a very similar outcome with (131)I-MIBG therapy (3-y-EFS 49 +/- 9%, 3-y-OS 59 +/- 10%) and without (131)I-MIBG therapy (3-y-EFS 33 +/- 9%, p = 0.171; 3-y-OS 59 +/- 9%, p = 0.285) due to the dominating effect of ASCT. By multivariate analysis, (131)I-MIBG therapy had no impact on EFS (p = 0.494) and OS (p = 0.891). Only ASCT, external beam radiation therapy and MYCN amplification were important for EFS and OS. CONCLUSIONS: An independent advantage of I-131-MIBG therapy could not be proven in this retrospective analysis. The ongoing German Neuroblastoma Trial NB2004 will address the influence of (131)I-MIBG therapy with emphasis on tumour dosimetry.