Evaluation of activity kinetics in breast milk and calculation of the resulting effective radiation dose after 99mTc-MIBI scintigraphy of a breastfeeding women.

INTRODUCTION: In breastfeeding women, the indication for scintigraphic imaging is strongly restricted due to potential transition of the radiopharmaceutical to the child via breast milk. The potential activity uptake of the breastfed child depends on the chemical compound of the radio pharmaceutical as well as biokinetics and metabolism in the maternal body. METHODS: In the presented case 99mTc-MIBI scintigraphy was performed in a breastfeeding woman with sonographically suspicious thyroid nodules. Breastfeeding was interrupted for 30 hours and the breast milk during this period was collected and analysed to determine the excreted activity and the potentially resulting dose to the breastfed child. RESULTS: Activity concentration in the first breast milk sample (1.83 hours after administration of 500 MBq 99mTc-MIBI) was 380 Bq/mL, resulting in an absolute activity of 50 kBq for a sample size of 132 mL. Subsequently activity concentration decreased to 6 Bq/mL (29.8 hours p.i.). The calculated effective half-life of the secretion of 99mTc-MIBI via breast milk was 4.7 hours. The potentially resulting effective dose for the breastfed child was 13.4 µSv (ICRP80: dose coefficient: 0.13 mSv/MBq for 99mTc). CONCLUSION: Time activity curve showed a rapid decrease of the 99mTc-MIBI activity secreted to the breast milk. More than 90 % of the total secreted activity is attributable to the first 12 hours after administration. Therefore, an interruption of breastfeeding of 24 hours seems to be adequate.

The influence of thyroid hormone medication on intra-therapeutic half-life of 131I during radioiodine therapy of solitary toxic thyroid nodules.

Despite a significantly improved dietary iodine supply, solitary toxic thyroid nodules (STN) are still a common clinical problem in former iodine deficient areas. Radioiodine treatment (RIT) is a well-established therapeutic option with few side effects and high success rates. As radioiodine biokinetics are individual for every patient, the necessary activity has to be calculated individually by a pre-therapeutic measurement of the intra-therapeutic effective half-life (EHL) in a radioiodine uptake test (RIUT). A suppressive medication with triiodothyronine (T3) or tetraiodothyronine (T4) is often needed to suppress uptake in normal thyroid tissue. Therefore, the aim of this study was to quantify the possible influence of this medication on intra-therapeutic radioiodine biokinetics. A cohort of 928 patients with STN undergoing RIUT and RIT was analysed. Patients were subdivided into 3 groups. Group T3: medication with T3 (n = 274), group T4: medication with T4 (n = 184) and group NM: no additional medication (n = 470). The T3 and T4 subgroups were further subdivided depending on the dose of thyroid hormone medication. In order to analyse the influence of thyroid hormone medication on individual intra-thyroidal biokinetics, the variance of the determined individual EHL between RIUT and RIT within the single groups and within the subgroups was investigated. EHL was significantly decreased between RIUT and RIT in the T3 and T4 subgroups (EHL: T3: 5.9 ± 1.1 d in RIUT and 3.3 ± 1.4 d in RIT (- 43%) (p < 0.05); T4: 5.9 ± 1.2 d in RIUT and 3.4 ± 1.5 d in RIT (- 42%) (p < 0.05). The decrease of EHL did not differ statistically between T3 or T4. However, both showed a highly significant difference compared to the NM group (p < < 0.05). A further subgroup analysis showed a significant dependence of the decrease in EHL related to the dose of thyroid hormone medication of 35-58% (T3) and 15-67% (T4) (p < 0.05). A significantly reduced EHL compared to RIUT in patients receiving thyroid hormone medication was detected. Moreover, a significant correlation between the dose of thyroid hormone medication (T3 or T4) and the decrease of EHL was found. Therefore, an adaption of the calculated activity should be considered in RIUT to obtain the required radiation dose in RIT of patients suffering from STN.

[Anticipating Criteria for Discharge after Lu-177-PSMA Treatment - Discussion of Several Scenarios]. / Vorausschauende Entlassungskriterien nach Lu-177-PSMA-Therapie ­ Diskussion unterschiedlicher Szenarien.

AIM: The aim is to add a pragmatic contribution to the discussion of an algorithm to discharge patients treated with Lu-177-PSMA under the aspect of radiation protection. This also may be applied to therapies with other radioactive tracers in the future. MATERIAL AND METHODS: 478 cycles of Lu-177-PSMA-617 (140 patients) were analyzed. The remaining activity in the patient and the dose rate were correlated. From frequent intratherapeutic measurements (biexponential fit) scenarios for discharging patients are deduced. RESULTS: Thirty-four per cent of all patients treated with Lu-177-PSMA received 3 to 5 cycles per calendar year. The dose limit of 1 mSv per calendar year (German Law) at a distance of 2 m from the patient would be exceeded in 10 % and 15 % of the treated patients if discharged 72 hours after treatment given 3 and 4 cycles per calendar year, respectively. Mean specific dose rate was 0.00462µSv/(h MBq) at a distance of 1 m. A universal correlation between dose rate and the remaining activity in the patient could not be found. CONCLUSION: The multi cycle concept of the therapies with Lu-177 PSMA has to be taken into account prospectively when discharging the patients. Given the physical half-life of Lu-177 an anticipation of 4 treatment cycles per calendar year leads to a clearly arranged, conservative rule.

[Comparison of 186Re to 662 keV photon radiation concerning biological radiation effect on the human B-cell line BV-173]. / Vergleich der biologischen Strahlenwirkung des ß--Emitters 186Re mit 662 keV Photonenstrahlung auf die humane B-Zelllinie BV-173.

ZIEL: Ziel der Untersuchung ist es, die Strahlenwirkung des ß--Emitters 186Re und von 662keV-Photonenstrahlung zu ermitteln, um die biologische Wirkung von Strahlung niedriger Dosisleistung (186Re) mit der hoher Dosisleistung zu vergleichen. MATERIAL UND METHODEN: Zellen der humanen Leukämie-Zelllinie BV-173 wurden mit 662keV-Photonenstrahlung respektive 186Re bestrahlt. In einem Inkubationszeitraum von 7 Tagen wurden Zahl und Vitalität der Zellen täglich bestimmt und als Dosiseffektkurven basierend auf der Vitalität dargestellt. Hierfür wurde der Zeitpunkt mit minimalem Überleben verwendet (72h 186Re und 24h Photonenstrahlung). ERGEBNISSE: Beide Strahlenarten zeigen am Auswertezeitpunkt (72h nach Versuchsbeginn für 186Re und 24h nach Versuchsbeginn für Photonenstrahlung) eine Überlebenskurve mit biexponentiellem Verlauf. Für Photonenstrahlung ist dies erklärbar durch eine Hypersensitivität im niedrigen Dosisbereich bis 1Gy, für die sich eine D0 von 3,3Gy ergibt, für Dosen über 1,0Gy liegt die D0 bei 10Gy. Für die 186Re-Inkubation ergibt sich eine D0 von 11,1Gy bei niedrigen Dosen verursacht durch die Reparatur subletaler Schäden, durch welche die biologische Wirkung abgeschwächt wird. Ab einer akkumulierten Dosis von etwa 1,6Gy zeichnet sich für 186Re ein wesentlich steilerer Kurvenverlauf mit einer D0 von 4,0Gy ab, der eine in diesem Bereich 2,5-fach stärkere biologische Wirkung als akute Photonenstrahlung wiedergibt (D0 4Gy für 186Re bzw. 10Gy für Photonen). SCHLUSSFOLGERUNG: Strahlung niedriger Dosisleistung zeigt eine geringere biologische Wirkung als eine akute Bestrahlung. Es existiert aber ein Grenzwert der akkumulierten Dosis, ab dem die biologische Wirkung von ß-Strahlung die der Photonenstrahlung sogar übertrifft.

[Evaluation of intratherapeutic 177Lu-HA-DOTATATE treatment in neuroendocrine tumors: dosimetry with SPECT, whole-body imaging and gamma probe]. / Evaluation der intratherapeutischen Dosimetrie bei der 177Lu-HA-DOTATATE Therapie neuroendokriner Tumoren mittels SPECT, Ganzkörperszintigraphie und Gammasonde.

AIM: Peptide receptor radionuclide therapy (PRRT) with 177Lu-HA-DOTATATE has evolved as a new path in the treatment of somatostatin-receptor-expressing neuroendocrine tumors. The kidneys are proven as organs at risk and should be evaluated dosimetrically. Overlap with other organs will make dosimetry based on planar scintigraphy inaccurate. Aim of this study was to approximate the contribution of the kidneys to conjugated planar views without the use of a SPECT/CT. MATERIAL AND METHOD: An algorithm was developed to determine the kidney dose using an EXCEL (Microsoft) based program. Dosimetric data were drawn and merged from three modalities: an individually calibrated gamma probe, a whole-body scintigraphy (WBS) and SPECT-acquisitions. The method was evaluated for 85 kidneys. Kidney masses were obtained via CT volumetry. RESULTS: The developed algorithm combines data from the three modalities. The ratio of the events within a kidney-VOI and the events from the summed coronary SPECT views (kidney ROI) represents the contribution of the kidney to the whole-body kidney ROI. This fraction was calculated to 49 % (17 % - 78 %) and 45 % (18 % - 75 %) for the left and the right kidney, respectively. Quantification of activity was deduced from equalizing the WBS count with the concurrent gamma probe measurement. Monoexponential curves were fitted to the obtained kidney activities, with resulting doses of 0,13 to 0,77 Gy/GBq (average 0,36 and 0,39 Gy/GBq for the left and the right kidney). CONCLUSION: The presented method is suitable to perform kidney dosimetry by using a gamma probe and a gamma camera, without using SPECT/CT.

Thyroid stunning in radioiodine-131 therapy of benign thyroid diseases.

PURPOSE: Existence and cause of thyroid stunning was controversially discussed for decades but the underlying mechanism remains unclear. Numerous studies describe thyroid stunning in radioiodine-131 therapy (RIT) of differentiated thyroid carcinoma. However, there are no studies evaluating thyroid stunning in benign thyroid diseases caused by the radioiodine uptake test (RIUT). Therefore, the influence of pre-therapeutic tracer radiation dose on therapeutic iodine-131 uptake was evaluated retrospectively. METHODS: A total of 914 RIT patients were included. Exclusion criteria were anti-thyroid drugs, pre- and/or intra-therapeutic effective half-lives (EHL) beyond 8.04 days and externally performed RIUT or 24 h RIUT. All patients received RIUT 1 week before RIT. Thyroid volume was estimated via ultrasound. Tracer radiation dose to the thyroid was calculated retrospectively. The dependence of changes in the pre-therapeutic to the therapeutic extrapolated-maximum-131I-uptake (EMU) from the dose in RIUT was evaluated statistically. RESULTS: EMU in RIUT ranged from 0.10 to 0.82 (median: 0.35) and EMU in RIT ranged from 0.10 to 0.74 (median: 0.33). Averaged over the whole cohort the therapeutic EMU decreased significantly (2.3% per Gray intra-thyroidal tracer radiation dose). A disease-specific evaluation showed dose-dependent thyroid stunning from 1.2% per Gray in solitary toxic nodules (n = 327) to 21% per Gray in goiters (n = 135) which was significant for the subgroups of disseminated autonomies (n = 114), multifocal autonomies (n = 178) and goiters (p < 0.05) but not for Graves' diseases (n = 160) and solitary toxic nodules (p > 0.05). CONCLUSIONS: The presented data indicate for the first time a significant dependence of pre-therapeutic radiation dose on thyroid stunning in goiter and disseminated and multifocal autonomy. To achieve the desired intra-thyroidal radiation dose, RIT activity should be adapted depending on the dose in RIUT.

[Influence of glucocorticoid therapy on intratherapeutic biodistribution of 131I radioiodine therapy in Graves' disease]. / Einfluss der Glukokortikoidtherapie auf die intratherapeutische Bio distribution von 131I bei der Radio jodtherapie des Morbus Basedow.

AIM: Radioiodine therapy (RIT) is an important therapeutic method in the definitive treatment of Graves' disease (GD). However, RIT may trigger development of Graves' ophthalmopathy (GO) or exacerbate a pre-existing GO. Therefore, the procedure recommendation of the DGN (German Society of Nuclear Medicine) for RIT of benign thyroid diseases recommends an additional glucocorticoid therapy for patients with pre-existing GO. Aim of this study was to analyze the influence of a protective glucocorticoid therapy on 131I biokinetics during RIT of patients with GD. MATERIAL AND METHODS: In this retrospective analysis 211 patients with GD who underwent RIT without additional thyreostatic medication were examined. To analyze 131I biokinetics the extrapolated maximum uptake (EMU) and the effective half-life of 131I in the thyroid were determined. Patients suffering from GO received glucocorticoids according to a fixed scheme starting one day prior to RIT, patients without GO did not receive glucocorticoids. Subsequently the ratios of values measured during RIT and those measured during radioactive iodine uptake test were compared among the groups. To take into account other factors, the groups were also compared regarding age, weight, TSH, TRAb, TgAb and TPOAb. RESULTS: In patients with additional glucocorticoid therapy, a reduction of the median EMU from 44 % in radioiodine uptake test to 35 % during RIT was observed. The pretherapeutic (47 %) and intratherapeutic (46 %) EMU of the control group without glucocorticoids remained constant. Comparison of the change in the EMU showed a statistically significant difference between both groups (p < 0.001). Comparison of all other parameters including the effective half-life of 131I (p = 0.79) did not show any statistically significant difference. CONCLUSION: The present study suggests that glucocorticoids affect the biokinetics of 131I by reducing its thyroidal uptake. As a result of this study, for patients without antithyroid medication undergoing glucocorticoid therapy, an adjustment of therapeutic 131I activity determined in radioiodine uptake test could be considered.

Evaluation of fear of radiation and isolation before and after radioiodine therapy.

BACKGROUND: Prior to undergoing radioiodine therapy (RIT), patients regularly have concerns about isolation on the ward (mandatory for RIT for at least 48 hours in Germany due to radiation protection legislation) as well as fear of the presence of radioactive substances. In this study, these fears were investigated before and after RIT. METHODS: A questionnaire was developed for completion both before and after radioiodine therapy. Questions included: (i) "Are you afraid of a therapy with radioactive substances?" (ii) "Do you have reservations about contact with radioactive substances?" and (iii) "Are you anxious about isolation?" Possible answers were made in a qualitative representation using a scale of 1-4 (4=full agreement, 3=mostly agreement, 2=partial agreement, and 1=no agreement). Further questions included, for example, sources of information used prior to therapy. A total of 209 patients treated by single or preplanned multiple RIT were surveyed over a period of 8 months (return 109). Analysis was done in subgroups according to age, education, disease, and number of RITs. RESULTS: Question 1, "Are you afraid of a therapy with radioactive substances?" showed a similar statistically relevant decline in each subgroup (p<0.05), except for patients with multiple RIT (p=0.81). Asked about the handling of radioactive substances and their perception about the safety in this regard, the entire collective showed a highly statistically significant (p<0.01) decrease with little variability between the groups. The question concerning fear of isolation resulted in a significant decrease (p<0.05) in all subgroups, except for patients with multiple RIT (p=0.13). Analysis of sources of information before RIT showed that older patients preferred printed material and rarely used online resources, while younger patients used the internet more frequently, in addition to printed materials. Finally, most patients would undergo radioiodine therapy again (medical indication provided), with 54% fully agreeing and only 4% not agreeing. CONCLUSIONS: The survey demonstrates a reduction in concerns about nuclear radiation, use of unsealed radioactive materials, and isolation on the ward after RIT. Surprisingly, concerns rise again before a subsequent therapy.

Acute myocardial infarction activates progenitor cells and increases Wnt signalling in the bone marrow.

AIMS: We aimed to characterize the influence of acute myocardial infarction (AMI) on the metabolic activity of the bone marrow (BM) and on the composition and functional activity of BM-derived mononuclear cells (BMC). Acute ischaemia or other stressors induce the mobilization of progenitor cells from the BM stem cell niche. The effect of AMI on the numbers and functional activity of cells within the BM is unknown. METHODS AND RESULTS: In patients of the REPAIR-AMI trial as well as in mice, the number and functionality of BMC was compared with respect to the time interval from AMI. Activation of Wnt signalling was assessed after AMI induction in TOP-GAL transgenic reporter mice, carrying a ß-galactosidase gene driven by an LEF/TCF/ß-catenin responsive promoter. The metabolic activity of the BM, as determined by F-18-fluorodeoxyglucose-positron emission tomography, was significantly higher in patients with AMI compared with patients with chronic post-ischaemic heart failure. Moreover, the number of haematopoietic CD34(+) (P < 0.05) and CD133(+) (P < 0.05) cells in the BM aspirates was significantly increased in patients within 7 days after AMI. In order to confirm these clinical data, we induced AMI in mice, which time-dependently increased the number of c-kit + Sca-1 + lin- cells and colony-forming units in the BM. Activation of the BM by AMI induced a significant increase in Wnt signalling, which is known to induce proliferation of haematopoietic stem cells, and demonstrated increased levels of the Wnt target Axin-2 in BM-derived cells on Day 7 (P < 0.01 vs. control). CONCLUSION: Acute myocardial infarction is associated with an increased metabolic activity and increased levels of progenitor cells within days after AMI. These findings document an activation of the stem cell niche within the BM following AMI, which may have important implications for the optimal timing of cell aspirations used for therapeutic application in patients with AMI.