Targeted radioligand therapy of metastatic castration-resistant prostate cancer (mCRPC) with 177Lu-PSMA (RLT) requires sufficient dose monitoring of the kidneys. Currently, dosimetry using SPECT/CT-imaging is the most preferred method. However, SPECT/CT is a time-consuming procedure and comprises additional radiation exposure to the patient. Moreover, not every therapeutic nuclear medicine facility has access to SPECT/CT. Therefore, the aim of this study was to develop a new procedure of kidney dosimetry without the use of SPECT/CT and evaluate this method in a large cohort of patients with mCRPC undergoing RLT. A dedicated torso phantom with kidneys filled with a solution of 177Lu-PSMA was used for quantitative calibration of a SPECT-camera. The calculated sensitivity was adapted according to the individual attenuation of the patient in four directions from the kidney surface to the body surface (ventral, dorsal, left and right) obtained from a previously performed CT. A total of 196 patients undergoing 926 cycles of 177Lu-PSMA therapy were retrospectively analyzed. Abdominal SPECT was performed 24, 48 and 72 h after administration of 177Lu-PSMA including scatter and dead-time correction in every patient. Kidney dose was calculated using an individual attenuation-based procedure and compared to values from international literature. Volumes of interest of the kidneys were drawn in the three sequential SPECT-images to calculate intra-renal effective half-life. Absolute quantification of activity in the kidneys was accomplished obtaining a patient individual sensitivity based on the individual attenuation in the patient. Kidney dose was then calculated applying a bi-exponential time activity curve in Microsoft EXCEL. Mean kidney dose per administered activity was 0.54 (± 0.26) Gy/GBq. With the presented procedure a reliable kidney dosimetry is possible without the use of SPECT/CT. Facilities without SPECT/CT are therefore able to perform an adequate kidney dosimetry without additional radiation exposure for the patient.

Graves' disease is one of the most common causes of hyperthyroidism. Guideline recommendations advocate the intake of thionamides for at least 1 year. If hyperthyroidism persists, subsequent radioiodine-131 treatment (RIT) is a therapeutic option. Thionamides are known to influence intra-thyroidal bio-kinetics of iodine and should therefore be discontinued at least 3 days prior to RIT if possible. However, the required therapeutic activity has to be calculated individually by pre-therapeutic measurement of the uptake prior to RIT [radioiodine-131 uptake test (RIUT)] in Germany according to national guidelines. Therefore, the aim of this study was to quantify the influence of thionamides on intra-therapeutic uptake. A cohort of 829 patients with Graves' disease undergoing RIUT and RIT was analysed. Patients were subdivided into three groups. Group A: patients with carbimazole medication (n = 312), group B: patients with methimazole medication (n = 252) and group C: patients without thionamides (n = 265). Group A and B were further subdivided depending on the reduction of dosage of thionamides. In order to analyse the influence of thionamides, the variance of the determined individual extrapolated maximum intra-thyroidal uptake (EMU) between RIUT and RIT within the single groups and within the subgroups was statistically evaluated. When administering an equal dose of thionamides or no thionamides in RIUT and RIT (groups A1, B1 and C) no significant differences were detected when comparing EMU in RIT to EMU in RIUT (p > 0.05). In the subgroups A2-A4 (reduced dosage of carbimazole prior to RIT) EMU was significantly increased in RIT compared to RIUT [21% for a reduction of 0 to < 10 mg/d (A2), 39% for a reduction of 10-15 mg/d (A3) and 80% for a reduction of > 15 mg/d (A4)]. In the subgroups B2-B4 (reduced dosage of methimazole prior to RIT) EMU was as well significantly increased in RIT compared to RIUT [26% for a reduction of 0 to < 10 mg/d (B2), 36% for a reduction of 10-15 mg/d (B3) and 59% for a reduction of > 15 mg/d (B4)]. A significant dose-dependent increase of EMU in RIT compared to EMU in RIUT in patients discontinuing or reducing thionamides was detected. Therefore, thionamides should be discontinued at least 2 days prior to RIUT in order to achieve the designated target dose more precisely and to minimize radiation exposure of organs at risk.

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.

Aim: Therapy success in patients with differentiated thyroid cancer (DTC) after thyroidectomy and radioiodine therapy (RIT) is proven by permanent decrease in human thyroglobulin (hTg) to <1 ng/mL. In this retrospective analysis hTg development before, during and after pregnancy were analyzed. Material and methods: A descriptive analysis of hTg courses in 47 women with 57 pregnancies under levothyroxine substitution was performed after treatment of DTC without evidence of residual or recurrent disease. We compared hTg levels before, during and after pregnancies. A median of four measurements were performed during pregnancy. Results: In five out of the 47 patients at least one hTg increase to ≥1.0 ng/mL occurred during pregnancy (P1: 1.1; P2: 1.75; P3: 1.0; P4: 1.1; P5: 1.07 ng/mL). In another three cases an increase to ≥0.5 ng/mL occurred. After delivery, all patients returned to undetectable hTg levels. Human Tg maxima during pregnancy were significantly elevated according to Friedman´s Chi2 and p Holm–Bonferroni. Conclusion: In women with ablative thyroid therapy after DTC, a temporary elevation in hTg levels during pregnancy may occur. The reason therefore remains unclear and requires further investigation.

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.

Abstract Background Myelosuppression is a potential dose-limiting factor in radioligand therapy (RLT). This study aims to investigate occurrence, severity and reversibility of hematotoxic adverse events in patients undergoing RLT with 177Lu-PSMA-617 for metastatic castration-resistant prostate cancer (mCRPC). The contribution of pretreatment risk factors and cumulative treatment activity is taken into account specifically. Methods RLT was performed in 140 patients receiving a total of 497 cycles. A mean activity of 6.9 $$\pm$$ ± 1.3 GBq 177Lu-PSMA-617 per cycle was administered, and mean cumulative activity was 24.6 $$\pm$$ ± 15.9 GBq. Hematological parameters were measured at baseline, prior to each treatment course, 2 to 4 weeks thereafter and throughout follow-up. Toxicity was graded based on Common Terminology Criteria for Adverse Events v5.0. Results Significant (grade ≥ 3) hematologic adverse events occurred in 13 (9.3%) patients, with anemia in 10 (7.1%), leukopenia in 5 (3.6%) and thrombocytopenia in 6 (4.3%). Hematotoxicity was reversible to grade ≤ 2 through a median follow-up of 8 (IQR 9) months in all but two patients who died from disease progression within less than 3 months after RLT. Myelosuppression was significantly more frequent in patients with pre-existing grade 2 cytopenia (OR: 3.50, 95%CI 1.08–11.32, p = 0.04) or high bone tumor burden (disseminated or diffuse based on PROMISE miTNM, OR: 5.08, 95%CI 1.08–23.86, p = 0.04). Previous taxane-based chemotherapy was associated with an increased incidence of significant hematotoxicity (OR: 4.62, 95%CI 1.23–17.28, p = 0.02), while treatment with 223Ra-dichloride, cumulative RLT treatment activity and activity per cycle were not significantly correlated (p = 0.93, 0.33, 0.29). Conclusion Hematologic adverse events after RLT have an acceptable overall incidence and are frequently reversible. High bone tumor burden, previous taxane-based chemotherapy and pretreatment grade 2 cytopenia may be considered as risk factors for developing clinically relevant myelosuppression, whereas cumulative RLT activity and previous 223Ra-dichloride treatment show no significant contribution to incidence rates.

Aim Aim of the study was to determine the effects of the beta-emitter Re-186 and 662 keV photon radiation in order to compare the biological effects of low dose rate (Re-186) to high dose rate irradiation. Methods Prae-B-lymphocytes were exposed to 662 keV photon radiation or incubated with a liquid solution of Re-186. Cell count and viability were compared over the observation period of seven days, survival curves constructed and analysed at time of lowest cell-viability. Results Biphasic cell survival curves resulted for both radiation types. Survival curves were obtained at 24 h for photon ra-diation and 72 h for Re-186. The biphasic survival curve after photon radiation exposure can be explained by radiation hypersensitivity at doses below 1 Gy resulting in a D-0 of 3.3 Gy. Doses exceeding 1.0 Gy showed a D-0 of 10 Gy. The biphasic survival curve in case of Re-186 incubation represents repair of sub lethal damage in the first section of the curve (D-0 11.1 Gy) -in this case, biological effects of the beta-emitter are attenuated by repair. Beyond an accumulated dose of 1.6 Gy, Re-186 showed a steeper slope with a D-0 of 4 Gy, corresponding to 2.5 times higher biological effects compared to acute photon irradiation (10 Gy). Conclusion Low dose rate radiation resulted in low biological effects at low doses. There is a threshold of accumulated dose above which biological effects of Re-186-incubation exceed those of photon irradiation.

Aim Peptide receptor radionuclide therapy (PRRT) with (177) Lu-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.

Zusammenfassung Ziel Bei der Behandlung somatostatinrezeptor-exprimierender neuroendokriner Tumoren hat sich in den letzten Jahren die Peptidrezeptor-Radionuklidtherapie (PRRT) mit 177Lu-HA-DOTATATE als neue Möglichkeit entwickelt. Da außer Tumor und Metastasen auch die Nieren Somatostatinrezeptoren besitzen, die Aktivität in diesen akkumuliert, sind sie als Risikoorgane einzustufen und sollten dosimetrisch evaluiert werden. Die Bestimmung der Nierenaktivität aus planaren Aufnahmen ist durch Überlagerung der Nieren mit anderen Organen ungenau und führt zu ihrer Dosisüberschätzung. Ziel dieser Studie war es, den Beitrag der Nieren in den konjugierten Sichten ohne SPECT/CT in der individuellen Nierendosimetrie zu berücksichtigen. Material und Methoden Für die Bestimmung der Nierendosis wurde ein Algorithmus entwickelt, der mit EXCEL (Microsoft) umgesetzt wurde. Die Patientenmessdaten aus drei Modalitäten einer individuell kalibrierten Gammasonde, einem Ganzkörperszintigramm und drei SPECT-Akquisitionen zu verschiedenen Zeitpunkten wurden hierfür zusammengeführt. Die Methode wurde mit Daten von 85 Nieren von Patienten, die mit 177Lu-HA-DOTATATE behandelt worden waren, evaluiert. Die Nierenvolumina wurden mittels CT-Volumetrie gewonnen. Ergebnisse Der entwickelte Algorithmus kombiniert die Daten aus drei Modalitäten: Gamma-Sonde, SPECT und Ganzkörperszintigraphie. Der Quotient aus den Ereignissen der Nieren-VOI und der Anzahl der Ereignisse in der Nieren-ROI des koronaren Summationsbildes ist der Beitrag der Niere im Summationsbild und repräsentiert somit über die Kalibrierung aus der Ganzkörperszintigraphie die Aktivität in der Niere. Da die Abbildungseigenschaften in den SPECT-Akquisitionen zu den verschiedenen Zeiten konstant sind, folgt aus dem Verlauf der Zählraten in den jeweiligen Nieren-VOIs auch der Aktivitätsverlauf in den Nieren. Daraus kann über einen monoexponentiellen Fit der Aktivitätsausscheidung unter Berücksichtigung der Akkumulationskinetik die Nierendosis bestimmt werden. Der mittlere Anteil in der Niere, bezogen auf deren Projektion im Summationsbild, wurde mit 49 % (17 %–78 %) und 45 % (18 %–75 %) für die linke bzw. rechte Niere berechnet. Die sich daraus ergebenden Nierendosen lagen zwischen 0,13 und 0,77 Gy/GBq (Mittelwerte 0,36 Gy/GBq und 0,39 Gy/GBq für die linke und die rechte Niere). Schlussfolgerung Die vorgestellte Methode eignet sich, um mit Gammasonde und Szintigraphie/SPECT (auch ohne SPECT/CT), eine individuelle Nierendosimetrie durchzuführen.

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- 131 I-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.

SummaryGermany has developed into a country with a nationwide largely sufficient iodine supply due to improved alimentary iodine supply. The reduction of iodine uptake in focal autonomies induced by reduced iodine avidity was evaluated by Gotthardt et al. 2006, showing a significant decline of pertechnetate uptake up to the year 2004. Aim: This study was intended to carry this investigation forward to the present day to analyze the course of a conjectural stabilization of iodine uptake values. Patients, material, methods: 283 patients who underwent radioiodine therapy for focal thyroid were analyzed retrospectively. Pertechnetate uptake was measured scintigraphically, thyroid volume sonographically and iodine uptake by iodine uptake test. The uptake percentage in the autonomous volume was correlated with autonomous volume and the resulting values tracked over a time period of seven years. Results : Mean thyroid volume ranged from 24 to 29 ml, autonomous volume from 7.2 to 9.4 ml. Pertechnetate uptake ranged from 0.2 to 0.25%/ml autonomous volume. Iodine uptake values ranged from 3.2 to 4.2%/ml autonomous volume. None of the changes observed were statistically significant (all p>0.05). Conclusion: Prophylactic measures towards improvement of the general public´s iodine supply in Germany had led to a decline of pertechnetate and iodine uptake in the thyroid up until the turn of the millennium. The here presented data show a stabilization of 99mTc-Uptake. Our study could also show that actual iodine uptake has stabilized at a steady level over the preceding seven years.

Germany has developed into a country with a nationwide largely sufficient iodine supply due to improved alimentary iodine supply. The reduction of iodine uptake in focal autonomies induced by reduced iodine avidity was evaluated by Gotthardt et al. 2006, showing a significant decline of pertechnetate uptake up to the year 2004.AIM:This study was intended to carry this investigation forward to the present day to analyze the course of a conjectural stabilization of iodine uptake values.PATIENTS, MATERIAL, METHODS:283 patients who underwent radioiodine therapy for focal thyroid were analyzed retrospectively. Pertechnetate uptake was measured scintigraphically, thyroid volume sonographically and iodine uptake by iodine uptake test. The uptake percentage in the autonomous volume was correlated with autonomous volume and the resulting values tracked over a time period of seven years.RESULTS:Mean thyroid volume ranged from 24 to 29 ml, autonomous volume from 7.2 to 9.4 ml. Pertechnetate uptake ranged from 0.2 to 0.25%/ml autonomous volume. Iodine uptake values ranged from 3.2 to 4.2%/ml autonomous volume. None of the changes observed were statistically significant (all p>0.05).CONCLUSION:Prophylactic measures towards improvement of the general public´s iodine supply in Germany had led to a decline of pertechnetate and iodine uptake in the thyroid up until the turn of the millennium. The here presented data show a stabilization of 99mTc-Uptake. Our study could also show that actual iodine uptake has stabilized at a steady level over the preceding seven years.

Germany has developed into a country with a nationwide largely sufficient iodine supply due to improved alimentary iodine supply. The reduction of iodine uptake in focal autonomies induced by reduced iodine avidity was evaluated by Gotthardt et al. 2006, showing a significant decline of pertechnetate uptake up to the year 2004. Aim: This study was intended to carry this investigation forward to the present day to analyze the course of a conjectural stabilization of iodine uptake values. Patients, material, methods: 283 patients who underwent radioiodine therapy for focal thyroid were analyzed retrospectively. Pertechnetate uptake was measured scintigraphically, thyroid volume sonographically and iodine uptake by iodine uptake test. The uptake percentage in the autonomous volume was correlated with autonomous volume and the resulting values tracked over a time period of seven years. Results: Mean thyroid volume ranged from 24 to 29 ml, autonomous volume from 7.2 to 9.4 ml. Pertechnetate uptake ranged from 0.2 to 0.25%/ml autonomous volume. Iodine uptake values ranged from 3.2 to 4.2%/ml autonomous volume. None of the changes observed were statistically significant (all p>0.05). Conclusion: Prophylactic measures towards improvement of the general public's iodine supply in Germany had led to a decline of pertechnetate and iodine uptake in the thyroid up until the turn of the millennium. The here presented data show a stabilization of Tc-99m-Uptake. Our study could also show that actual iodine uptake has stabilized at a steady level over the preceding seven years.

BACKGROUNDPrior 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.METHODSA 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.RESULTSQuestion 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.CONCLUSIONSThe 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.