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According to the requirements of radiation protection legislation, patients may only be discharged from the nuclear medicine therapy ward if it is ensured that the cumulative radiation exposure of the population is below 1 mSv per year. In the present study, dose measurements of patients after radioiodine therapy (RIT) and their relatives are to be used to prove that the radiation exposure resulting from the medical application is low and that the legal framework conditions are complied with. Furthermore, the results allow conclusions to be drawn about the measurement accuracy of the dosimeters used.Methods: In 147 patients after RIT and their relatives, the dosage was measured over 14 days with different measuring systems. Finger ring dosimeters (FRD) were worn during the whole day, furthermore the dose was determined by non-official OSL and TLD dosimeters during the sleep phase.Results: 88 data sets were used for the final analysis. With the FRD, dose values between 0.1–50 mSv were determined for the patients. As expected, the finger ring dose of the relatives was significantly lower, averaging 0.75 mSv compared to 10 mSv for the patient. For the TLD and OSL used in the sleep phase, the measured values were in the same range. The reproducibility of the measurement results was significantly better for the OSL than for the TLD.Conclusion: Despite method-related measurement uncertainties, it can be concluded that the exposure dose of patients’ relatives after radioiodine therapy is low and that the legal requirements are met. Moreover, the now official OSL dosimeters represent a more accurate and for the chosen measurement task better suited measurement system than the TLD. Key Points: Citation Format

Zusammenfassung Ziel Die neue Strahlenschutz-Gesetzgebung sieht vor, dass eine Risikoanalyse neuer und bestehender Behandlungsverfahren mit offenen Radionukliden hinsichtlich der Patientensicherheit wiederkehrend durchzuführen ist, in welche der Medizinphysik-Experte maßgeblich involviert ist. Material und Methoden Als Werkzeug für die Durchführung der Risikoanalyse wurde die Fehlermöglichkeits- und Einflussanalyse (FMEA) angewendet, wie vom Bundesamt für Strahlenschutz (BfS) und den Fachgesellschaften empfohlen. Für die Radiojodtherapie, die Radiosynoviorthese, die Peptid-Radiorezeptortherapie und die selektive interne Radiotherapie wurden die Prozesse gegliedert und zunächst individuell durch die verschiedenen am Prozess beteiligten Berufsgruppen und anschließend im Konsens kategorisiert. Für Risikoprioritätszahlen > 125 wurden Gegenmaßnahmen erarbeitet. Die Risikoprioritätszahl (RPZ) ergibt sich als Produkt aus dem Schweregrad, der Auftretenswahrscheinlichkeit und der Entdeckungswahrscheinlichkeit des Fehlers oder der Folgen. Ergebnisse Neben den diversen Möglichkeiten der Verwechslung von Patienten wurden Unsicherheiten in der Aktivitäts- und Organgrößenbestimmung und eine mangelnde Compliance des Patienten als wesentliche Risiken für eine Unter- oder Übertherapie angesehen. Die ausgeprägte Streuung bei individueller Risikobetrachtung durch einzelne Berufsgruppen konnte unter Anleitung durch einen externen Moderator deutlich reduziert werden. Für die höchsten RPZ wurden Maßnahmen formuliert, deren präventive Wirkung im Verlauf noch zu überprüfen ist. Schlussfolgerung Die nuklearmedizinische Therapie wurde in der organisatorischen Durchführung als sehr sicher eingeschätzt und es wurden nur geringe Risiken bzgl. der Patientensicherheit identifiziert. Die FMEA-Analyse war ein praktikables Instrument und identifizierte Prozessschritte mit Optimierungspotenzial für die analysierten Therapieformen. Das geschilderte Vorgehen kann in anderen nuklearmedizinischen Einrichtungen adaptiert werden, wobei strukturspezifische Faktoren (technische und personelle Ausstattung, Ablauf von Prozeduren) zu berücksichtigen sind, sodass ggf. weitere Risiken identifiziert und hier aufgeführte Risiken aufgrund anderer Abläufe als abweichend eingeschätzt werden können.

A 65-year-old woman with a long history of metastasized, highly differentiated (G1) neuroendocrine tumor of pancreatic origin presented for follow-up Ga-DOTATATE PET/CT after 7 peptide receptor radiotherapies. In the previous scan, she already had discrete intracranial tracer accumulations, which were massively progressive in the recent Ga-DOTATATE PET/CT 8 months later. This case illustrates that cerebral metastases in neuroendocrine tumors may occur many years after initial diagnosis, and their somatostatin receptor expression may rise within a few months to a level that reasonably justifies further peptide receptor radiotherapy.

Summary Aim: Besides the use of somatostatin analogues, small molecules like sunitinib and everolimus as well as conventional chemotherapy, peptide receptor radiotherapy (PRRT) using radiolabelled somatostatin analogues has gained an important role in the treatment of inoperable, metastasized neuroendocrine tumours (NET). There are various radiotracers in use. Based on our experience with the PET tracer [68Ga]DOTA-3-iodo- Tyr3-octreotate ([68Ga]HA-DOTATATE), a DOTATATE derivative with an increased binding affinity to hsst5, the current retrospective analysis is exploring the therapeutic potential of [177Lu]HA-DOTATATE. Methods: Eighteen patients with metastatic NET (G1/G2) were treated using [177Lu]DOTATATE and/or [177Lu]HA-DOTATATE, and dosimetric results of both tracers were compared. Results: Using [177Lu]HA-DOTATATE, a mean tumour dose of 5.34 Gy/GBq (median 2.53 Gy/ GBq; range 0.89-33.3 Gy/GBq) was achieved, while [177Lu]DOTATATE delivered a tumour dose of 5.53 Gy/GBq (median 2.70 Gy/GBq; range 0.44-15.3 Gy/GBq). Organ doses for [177Lu]HA-DOTATATE vs. [177Lu]DOTATATE were as follows: kidney 2.31 ± 0.85 vs. 2.03 ± 0.96 Gy/GBq, liver 1.6 ± 0.79 vs. 1.67 ± 1.73 Gy/GBq, spleen 3.89 ± 4.04 vs. 4.50 ± 3.69 Gy/GBq and whole body 0.16 ± 0.10 Gy/GBq vs. 0.15 ± 0.08 Gy/ GBq. Tumour-to-kidney dose ratio was slightly higher for [177Lu]DOTATATE (2.4 ± 5.6) compared to [177Lu]HA-DOTATATE (1.5 ± 3.6). Conclusion: Both tracers showed marked inter-patient variation in their dosimetry, and no significant differences in dosimetry of [177Lu]HA- DOTATATE and [177Lu]DOTATATE were observed when taking all patients into account. Thus, [177Lu]HA-DOTATATE appears viable for PRRT, although it was marginally inferior regarding kidney dose and tumour-to-kidney dose ratio compared to the established [177Lu]DOTATATE.

A 68-year-old woman who underwent a thyroidectomy for bilateral goiter 20 years ago was referred to our department. The examination revealed a newly occurred thyroid nodule in the right central lobe. Unexpectedly the Tc-pertechnetate scan revealed several extrathyroidal foci right-sided supraclavicular, beside a cold thyroid nodule in the right lower lobe. Consecutive surgery and histology confirmed the suspected diagnosis of follicular thyroid cancer with multiple bone metastases. Whole-body scintigraphy performed after the following radioiodine therapy indicated disseminated osseous metastases.

Over recent decades interest in diagnosis and treatment of neuroendocrine tumours (NET) has steadily grown. The basis for diagnosis and therapy of NET with radiolabelled somatostatin (hsst) analogues is the variable overexpression of hsst receptors (hsst1-5 receptors). We hypothesized that radiometal derivatives of DOTA-iodo-Tyr(3)-octreotide analogues might be excellent candidates for somatostatin receptor imaging. We therefore explored the diagnostic potential of (68)Ga-DOTA-iodo-Tyr(3)-octreotate [(68)Ga-DOTA,3-iodo-Tyr(3),Thr(8)]octreotide ((68)Ga-HA-DOTATATE; HA, high-affinity) compared to the established (68)Ga-DOTA-Tyr(3)-octreotate ((68)Ga-DOTATATE) in vivo.The study included 23 patients with known somatostatin receptor-positive metastases from NETs, thyroid cancer or glomus tumours who were investigated with both (68)Ga-HA-DOTATATE and (68)Ga-DOTATATE. A patient-based and a lesion-based comparative analysis was carried out of normal tissue distribution and lesion detectability in a qualitative and a semiquantitative manner.(68)Ga-HA-DOTATATE and (68)Ga-DOTATATE showed comparable uptake in the liver (SUVmean 8.9 ± 2.2 vs. 9.3 ± 2.5, n.s.), renal cortex (SUVmean 13.3 ± 3.9 vs. 14.5 ± 3.7, n.s.) and spleen (SUVmean 24.0 ± 6.7 vs. 22.9 ± 7.3, n.s.). A somewhat higher pituitary uptake was found with (68)Ga-HA-DOTATATE (SUVmean 6.3 ± 1.8 vs. 5.4 ± 2.1, p 0.05). On a lesion-by-lesion basis a total of 344 lesions were detected. (68)Ga-HA-DOTATATE demonstrated 328 lesions (95.3% of total lesions seen), and (68)Ga-DOTATATE demonstrated 332 lesions (96.4%). The mean SUVmax of all lesions was not significantly different between (68)Ga-HA-DOTATATE and (68)Ga-DOTATATE (17.8 ± 11.4 vs. 16.7 ± 10.7, n.s.).Our analysis demonstrated very good concordance between (68)Ga-HA-DOTATATE and (68)Ga-DOTATATE PET data. As the availability and use of (68)Ga-HA-DOTATATE is not governed by patent restrictions it may be an attractive alternative to other (68)Ga-labelled hsst analogues.

Background This paper describes the feasibility of intra-arterial high-activity administration of (188)Re-microspheres. Methods Patients with unresectable colorectal liver metastases or hepatocellular cancer (HCC) received single treatments with (188)Re-microspheres. The administered activity was calculated to give a liver dose of 100 Gy. From post-therapeutic scans and urine sampling, the dose to the liver, metastases and bladder was calculated. Toxicity was assessed up to 3 months after administration by means of the Common Terminology Criteria for Adverse Events v3.0 (Trotti et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003;13(3):176-81). Response was evaluated on CT. Results 13.6 +/- 4.7 GBq (188)Re-microspheres was administered selective in the feeding artery of the tumour to 10 patients (3 x HCC and 7 x colorectal liver metastases). There was a low urinary excretion rate of 8.9 +/- 3.8% of administered activity within 96 h. The absorbed dose to the tumour, normal liver (excluding the tumour) and bladder was 10.24 +/- 5.02 Gy/GBq (128 +/- 47 Gy), 3.94 +/- 2.52 Gy/GBq (50 +/- 33 Gy) and 0.27 +/- 0.20 Gy/GBq (2.4 +/- 1.9 Gy), respectively. There was an acceptable rate of toxicity in 30% of grades I and II, respectively, and 10% with grade III. There was reversible in the most patients within 14 days after treatment. The response was assessed on CT: two patients had a partial response (PR), five patients had stable disease and three patients had disease progression. Conclusion Treatment of colorectal liver metastases or HCC using high activities of (188)Re-microspheres was well tolerated and a PR was seen in 2 of 10 patients. The treatment represents a therapeutic option in these patients.

Objectives Myocardial perfusion SPECT is frequently affected by artefacts related to abdominal activity. Metoclopramide has been suggested to relieve this, but two previous studies have shown conflicting results. Methods Ninety-five patients received 10mg metoclopramide orally after injection of 99m Tc-tetrofosmin for the stress scan and 86 patients had metoclopramide after their rest injection. A control group of 82 patients did not receive metoclopramide. Scans were evaluated visually by three readers. Results Metoclopramide given before the stress scan led to abdominal activity being visually better in 16 scans, worse in 10, and unchanged in 67 scans, compared to the same patient's rest scan without metoclopramide administration. Metoclopramide administered before the rest scan resulted in abdominal activity in 11 scans being visually better, in 19 worse, and 53 scans were deemed unchanged. These differences were not significant. The number of repeat stress or rest scans was not significantly different between patients who had received metoclopramide and those who had not. The administration of metoclopramide, irrespective of whether it was given before the stress or rest scan, made no significant difference to inferior wall-to-abdomen count ratio. Conclusion Neither qualitative nor quantitative analysis showed an effect of metoclopramide on abdominal activity in myocardial perfusion SPECT.

OBJECTIVES: This study describes the practical implementation of X-ray-based attenuation correction (AC) of myocardial perfusion scans in a large teaching hospital, characterizes the impact of AC on the diagnostic confidence of the interpreter and tries to predict which patients are likely to benefit from the technique. METHODS: One hundred and seven consecutive patients underwent a 2 day (99m)Tc-tetrofosmin protocol with adenosine stress using GE Millennium VG with AC and ECG-gated acquisition (ECG-g). The diagnostic impact of AC/ECG-g was judged by a panel of three observers. RESULTS: AC was not achieved in 46 patients. Individual observers rated AC 'essential' in 37 scans and 'helpful' in 68 scans. For ECG-g, this applied to 12 and 78 scans, respectively. The rating for AC was better than that for ECG-g in 57 scans, and vice versa in 31 scans. Equal ratings were recorded in 41 scans, and neither technique was needed in 54 scans. Diagnostic interpretation of abnormal scans was significantly more likely to benefit from either AC or ECG-g than interpretation of normal scans. Patients in whom AC was considered useful had a significantly higher body mass and chest circumference, but the overlap was large. CONCLUSIONS: In practice, AC was not feasible in a significant proportion of our patients. AC received better ratings from observers more often than ECG-g. Interpreter confidence with AC was significantly greater in scans with perfusion defects than in normal scans. Body mass and chest circumference cannot be used to predict which patients will benefit from AC.

SummaryPurpose: 68Ga-labelled compounds are increasingly used for somatostatin-receptor scintigraphy because of their favourable biokinetic properties, a higher tumour-to- background contrast and higher diagnostic accuracy compared to the gamma-emitting tracer 111In-DTPA-octreotide. Recently, we have introduced the new tracer 68Ga-DOTA- 3-iodo-Tyr3-Thr8-octreotide (68Ga-HA-DOTA- TATE). The present study demonstrates the biodistribution and radiation dosimetry of this tracer in humans. Patients, methods: Seven men were enrolled in this analysis. Every patient underwent a 20 min dynamic PET scan after intravenous injection of about 114 ± 9 MBq of 68Ga-HA-DOTATATE. This was followed by two whole-body scans at 30 min p. i. and 120 min p. i. Blood radioactivity concentration was determined non-invasively from a ROI drawn over the aorta. Urine was collected until the time of the last scan. Liver, spleen, kidneys and urinary bladder wall were included in the dosimetric estimation that was carried out with the software package OLINDA 1.0. Results: Physiological 68Ga- HA-DOTATATE uptake was observed in the pituitary gland, thyroid, salivary glands, liver, spleen, kidneys, urinary bladder, adrenals and intestine. Organs with the highest absorbed dose were spleen (0.26 ± 0.11 mSv/MBq), kidneys (0.14 ± 0.03 mSv/MBq) and liver (0.12 ± 0.02 mSv/MBq).The estimated effective dose was 0.024 ± 0.001 mSv/MBq. Conclusion: Our study demonstrates biokinetics and radiation exposure of the 68Ga-labelled tracer HA-DOTATATE to be comparable to other 68Ga-labelled SSR analogues in clinical use.

The aims of this study were to determine the quantitative parameters of ventilation (V) and perfusion (Q) PET scans assessing V/Q quotients in patients with various lung pathologies, as well as the influence of patient position on regional perfusion patterns.Fifty-three patients (24 male and 29 female) underwent lung scintigraphy with (68)Ga-labelled radiopharmaceuticals. (68)Ga Galligas and B20 microspheres used for V and Q imaging were produced in-house. Images were acquired under a standard setup with two emission scans of the whole lung in the supine (S) position (acquisition time 3 min/bed position) on a PET/CT scanner combined with low-dose computed tomography (CT) for attenuation correction. In 27 patients the Q scan was repeated in the prone (P) position. Parametric images were calculated (V/Q, P/S when applicable) for each patient. Patients were grouped according to diagnostic findings, and V/Q ratio distributions were further analysed. Gradients of the regional blood flow in both the supine and prone position were calculated.The results from visual interpretation could be confirmed with parametric images. Voxel-wise V/Q analysis revealed significant differences in descriptive parameters such as median, mean and SD between normal patients and patients with acute and previous pulmonary embolism. Skewness and kurtosis were not significantly different. The effect of gravitation could be demonstrated by significant position-dependent changes of the gradients in the ventral-dorsal and apical-basal directions.PET/CT using (68)Ga-labelled tracers allows the application of quantitative procedures to improve functional pulmonary imaging in clinical diagnosis and research.

Since the introduction of somatostatin receptor (sst) imaging using I-Tyr-octreotide [1], peptide receptor imaging and radiotherapy (PRRT) has become an established modality in the management of neuroendocrine tumours (NET) [2]. Based on the findings of a previous study [3] investigating metal-labelled DOTA-octreotides substituted at Tyr, we hypothesized that derivatives of DOTA-iodo-Tyr-octreotide might be excellent candidates for sstr imaging and therapy. Consequently, we evaluated Ga-DOTA-iodoTyr-octreo tate (Ga-HA-DOTATATE; HA, high affinity) in vitro and in a preliminary PET study. As hypothesized, Ga-HADOTATATE showed high affinity for human sst2,5 as well as diagnostic and logistical advantages, i.e. unlimited precursor availability. The (Leu,D-Trp, [I]Tyr)-SST28 IC50 values (in nanomoles) for Ga-HA-DOTATATE were >10.000 (sst1), 0.64±0.23 (sst2), >1,000 (sst3 and sst4) and 59.7±15.1 (sst5), and for Ga-DOTATATE were >10,000 (sst1), 0.67±0.25 (sst2), >1.000 (sst3), 822±327 (sst4) and >1,000 (sst5). In a first PET study a 73-year-old patient suffering from a NETwith unknown primary and liver metastases was investigated with Ga-HA-DOTATATE and Ga-DOTATATE. Both agents showed a possible small primary tumour in the midgut and five liver metastases that showed somewhat higher Ga-HA-DOTATATE uptake (mean SUVmax 23.8 vs. 21.6). The visual detectability of three small liver metastases with low uptake was superior with Ga-HADOTATATE. In summary, Ga-HA-DOTATATE provides high-quality images comparable to or better than those with GaDOTATATE. Further clinical studies are needed to confirm these first results and explore the use of HA-DOTATATE agents for PRRT.

Prostate cancer (PCA) is the second most common tumour in men worldwide. Whereas prostate specific antigen (PSA) is an established biochemical marker, the optimal imaging method for all clinical scenarios has not yet been found. With the rising number of PET centres there is an increasing availability and use of (18)F-/(11)C-choline or (11)C-acetate for staging of PCA. However, to date no final conclusion has been reached as to whether acetate or choline tracers should be preferred. In this review we provide an overview of the performance of choline and acetate PET for staging the primary and recurrent disease and lymph nodes in PCA, based on the literature of the last 10 years. Although predominantly choline has been used rather than acetate, both tracers performed in a similar manner in published studies. Choline as well as acetate have insufficient diagnostic accuracy for the staging of the primary tumour, due to a minimum detectable tumour size of 5 mm and inability to differentiate PCA from benign prostate hyperplasia, chronic prostatitis and high-grade intraepithelial neoplasia. Regarding lymph node staging, choline tracers have demonstrated a high specificity. Unfortunately, the sensitivity is only moderate. For staging recurrent disease, sensitivity depends on the level of serum PSA (PSA should be2 ng/ml). This applies to both choline and acetate. However, despite these limitations, a significant number of patients with recurrent disease can benefit from PET imaging by a change in treatment planning.

Purpose Somatostatin binding to somatostatin receptors (SSTRs) is known to have an antiproliferative effect in neuroendocrine tumours. Melanoma cells are derived from the neural crest and thus express SSTR. Treatment options in metastasized melanomas are limited. Therefore, we aimed to investigate whether there is a relevant uptake of the SSTR analogue DOTATOC in metastasized melanoma patients, which could be used for therapy with radiolabelled SSTR analogues. Materials and methods We investigated 18 patients (nine men and nine women; mean age 61 years) with metastasized melanoma using PET/CT, first with F-18 fluorodeoxyglucose ((18)F-FDG) and then with Ga-68 DOTATOC. The number of (18)F-FDG-positive or DOTATOC-positive lesions and the maximum standardized uptake value (SUV(max)) for an index lesion were determined for each patient. Results DOTATOC could reveal metastatic lesions in 11 of 18 patients (61%). However, on a lesion-by-lesion basis only 59 of 263 (22%) (18)F-FDG-avid metastases were seen with DOTATOC. Further, DOTATOC uptake was only faint. The mean SUV(max) was 3.1 (range, 1.2-4.2) for DOTATOC, in contrast to 28.2 (range, 2.3-115) for (18)F-FDG. Conclusion Radiolabelled DOTATOC does not seem to be a promising agent for treatment of metastasized melanoma.

Recovery of spatial resolution lost through increasing lesion-to-detector distance can improve the spatial resolution of planar images. We compare two commercial solutions, HiScan (http://www.scivis.de) and Xact.bone (http://www.ultraspect.com), with unprocessed planar whole-body bone scans. Thirty-five patients with suspected bone metastases were scanned 3 h after injection of 600 MBq (99m)Tc-HMDP at 12 cm/min. Two patients with more than 20 lesions were used for reporter training and were excluded from the analysis. Two blinded reporters categorized each scan as benign, indeterminate or malignant and assigned individual lesions to those same categories. Image quality was first graded on a 1 (worst) to 10 (best) scale for each individual scan, and then all three scans of each patient were ranked according to image quality. Reporter A detected 65, 90 and 83 malignant lesions with the unprocessed scan, HiScan and Xact.bone and 23, 24 and 17 indeterminate lesions, respectively. Reporter B detected 60, 80 and 75 malignant lesions with the unprocessed scan, HiScan and Xact.bone and 17, 16 and 14 indeterminate lesions, respectively. To summarize, reporters A/B detected 38/33% and 28/25% more malignant lesions with HiScan and Xact.bone than with the unprocessed scan, respectively (Friedman's test, P

Somatostatin receptor scintigraphy is an established modality for imaging well-differentiated neuroendocrine tumors. It is known that inflammatory diseases (eg, tuberculosis) may also accumulate somatostatin receptor analogs. Here, we present the case of a 69-year-old patient with a neuroendocrine tumor of the rectum showing uptake of Ga DOTATATE in 2 vertebrae that was caused by vertebral hemangiomas. This could be clearly demonstrated on the CT scan. Although studies outlining the normal distribution of Ga DOTATATE exist, uptake in vertebral hemangiomas has not been described yet. As the case shows, vertebral hemangiomas should be kept in mind as a benign differential diagnosis.