[Positron emission tomography 2013 in Germany. Results of the query and current status]. / Positronenemissionstomographie 2013 in Deutschland. Ergebnisse der Erhebung und Standortbestimmung.

AIM: Five years after the first survey the positron emission tomography (PET) council of the German Society of Nuclear Medicine (DGN) repeated a survey to re-evaluate the status of PET diagnostics in Germany based on the data of the year 2013. METHODS: A web-based questionnaire was used for gathering information retrospectively. Details regarding the physicians involved in PET operations, PET systems, and radiopharmaceuticals were also part of the survey as well as indications and number of studies. Furthermore, the role of PET and PET/CT within the diagnostic process was evaluated. In addition, official statistical hospital reports were analysed. RESULTS: Responses from 52 sites were analysed. They reported a total of 38,350 PET studies in 2013. In the majority of cases PET was used in oncologic indications (87%). Further main applications were: neurology 6%, cardiology 1%, and inflammation 5%. University or other hospitals performed 85% of the studies. The portion of in-patients was 26%. Hybrid systems (56 PET/CT, 5 PET/MRT, and 2 stand-alone PET) were most frequently used for imaging. The radiotracers were labelled with F-18 in 90% of the studies, whereas Ga-68 was used in 9% and C-11 in 1%. Lung tumours were the most investigated tumour entity (40%), followed by malignant lymphoma (8%), tumours of the gastrointestinal tract (5%), and NET (5%). 20% of the 333 physicians hold a PET certificate awarded by the DGN. More than 50% of the facilities were certified according ISO9001, KTQ or QEP standard. The findings of nearly 60% of the oncological studies were discussed interdisciplinary in a tumour board. In federal statistical reports a 56% increase of in-patient PET operations during 5 years was found. CONCLUSION: In Germany, a moderate increase (9% per year) of PET studies is observed, but compared with other industrialised countries PET is still less established.

Dosimetric measurements of (68)Ga-high affinity DOTATATE: twins in spirit - part III.

PURPOSE: 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-DOTATATE). 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.

Evaluation of PET quantification accuracy in vivo. Comparison of measured FDG concentration in the bladder with urine samples.

UNLABELLED: Quantitative positron emission tomography (PET) requires accurate scanner calibration, which is commonly performed using phantoms. It is not clear to what extent this procedure ensures quantitatively correct results in vivo, since certain conditions differ between phantom and patient scans. AIM: We, therefore, have evaluated the actual quantification accuracy in vivo of PET under clinical routine conditions. PATIENTS, METHODS: We determined the activity concentration in the bladder in patients undergoing routine [18F]FDG whole body investigations with three different PET scanners (Siemens ECAT EXACT HR+ PET: n = 21; Siemens Biograph 16 PET/CT: n = 16; Philips Gemini-TF PET/CT: n = 19). Urine samples were collected immediately after scan. Activity concentration in the samples was determined in well counters cross-calibrated against the respective scanner. The PET (bladder) to well counter (urine sample) activity concentration ratio was determined. RESULTS: Activity concentration in the bladder (PET) was systematically lower than in the urine samples (well counter). The patient-averaged PET to well counter ratios for the investigated scanners are (mean ± SEM): 0.881 ± 0.015 (ECAT HR+), 0.898 ± 0.024 (Biograph 16), 0.932 ± 0.024 (Gemini-TF). These values correspond to underestimates by PET of 11.9%, 10.2%, and 6.8%, respectively. CONCLUSIONS: The investigated PET systems consistently underestimate activity concentration in the bladder. The comparison of urine samples with PET scans of the bladder is a straightforward means for in vivo evaluation of the expectable quantification accuracy. The method might be interesting for multi-center trials, for additional quality assurance in PET and for investigation of PET/MR systems for which clear proof of sufficient quantitative accuracy in vivo is still missing.

Sodium-iodide symporter positive cells after intracellular uptake of (99m)Tc versus α-emitter 211At. Reduction of clonogenic survival and characterization of DNA damage.

PURPOSE: We evaluated the DNA damaging potential of Auger electrons emitted in the decay of (99m)Tc compared to α-particles of 211At. MATERIAL AND METHODS: The impact of (99m)Tc and 211At was monitored in a NIS-expressing rat thyroid cell model PCCl3 with varying, yet defined intra- and extracellular radionuclide distribution (using ± perchlorate). The radiotoxicity of (99m)Tc and 211At was studied by the comet assay under neutral and alkaline conditions and colony formation. RESULTS: In the presence of perchlorate, the radioactivity yielding 37% cellular survival, A37, was estimated to be (0.27 ± 0.02) MBq/ml and (450 ± 30) MBq/ml for 211At and (99m)Tc, respectively. In absence of perchlorate, cellular radiotracer uptake was similar for both radionuclides (2.2%, 2.7%), yet the A37 was reduced by 82% for the α-emitter and by 95% for (99m)Tc. Cellular dose increased by a factor of 5 (211At) and 38 (99mTc). Comet assays revealed an increased DNA damage after intracellular uptake of both radiotracers. CONCLUSIONS: The data indicate damage to the cell to occur from absorbed dose without recognizable contribution from intracellular heterogeneity of radionuclide distribution. Comet assay under alkaline and neutral conditions did not reveal any shift to more complex DNA damage after radionuclide uptake. Cellular uptake of (99m)Tc and 211At increased cellular dose and reduced clonogenic survival.

[Measurement of ocular lens ionizing radiation exposure after radioiodine therapy]. / Bestimmung der Augenlinsenexposition bei Patienten nach einer Radioiodtherapie.

AIM: Current reports for the radiation cataracts contained a warning for deterministic effects at 1-2 Gy radiation single exposure for lens. Recently, the German Radiation Protection Board (SSK) published a document (234. SSK-Board) in that threshold dose for radiation cataracts is claimed at 0.5 Gy. The lens of the eye is recognized as one of the most radiosensitive tissues in the human body, and the International Commission on Radiological Protection (ICRP 103) has defined a limit of 150 mSv for its exposure.Recently, the ICRP lowered this limit down to 20 mSv per year.However, this limit does not apply to patients. Therefore, the question of the lens radiation exposure for patients underwent a radioiodine therapy (RIT) is a point at issue. PATIENTS, METHODS: A total of 41 patients (age: 22-92 years) underwent a radioiodine therapy were included in the study. Optical stimulated luminescence dosimeters were used to measure the radiation exposure. The dosimeters were fastened nearby the patient's eye lens. The measurement was carried out up to 48 h after radioiodine application and the patients were divided into three groups. Group 1: patients underwent a diagnostic 131I whole body scan (mean activity: 370 MBq); group 2: thyriod carcinoma patients under RIT (mean activity: 3700 MBq); group 3: hyperthyroid patients under RIT (activity: 180-1237 MBq). RESULTS: The cumulative exposure of the eye lens during the stay at the therapy unit (48 h) was 4.8 ± 0.7 mGy in group 1, 24.5-50.5 mGy in group 2 and 2.7-26.3 mGy in group 3, respectively. For the calculation of the expected cumulative dose, including follow-up after patient's dismissal, the effective half-lives were involved. The cumulative doses were obtained to be 6 ± 1 mGy in the first group, 63 ± 15 mGy in the second and 5-148 mGy in the third. CONCLUSION: The results show that there exists a low risk for radiation cataract in a nuclear medicine therapy unit. After serial radioiodine therapies radiation-induced lens opacity cannot be expected.

[Inventory resources of nuclear medicine]. / Mandat(e) für die Nuklearmedizin. Eine Inventur der Ressourcen.

AIM: The first survey of the German Society of Nuclear Medicine (DGN) to assess the resources of our speciality named "Inventory Resources of Nuclear Medicine" aims to provide a reliable data basis for existing and future activities of the DGN. The involvement and participation of as many colleagues as possible will play an important role for the success of the development of our profession. METHODS: 214 leading nuclear medicine professionals were identified as the target group. The questionnaire contained 13 different categories. Apart from individual-related questions, memberships in other societies as well as activities in federal or governmental boards, professional self-government or support groups were inquired. Participation in guideline programmes as well as other special experiences, knowledge or contacts, which could be relevant for the work of our boards and working groups, were also subject of the survey. RESULTS: The data of 112 (52.3%) returned questionnaires were analysed. 57 persons state that they have already been involved in the activities of the DGN. Almost three quarters of these persons (n = 42) explicitly affirm their further commitment to the DGN in the future. Another 35 respondents can envisage such a future commitment for themselves. More than half of all colleagues (n = 69) are members of a regional society of nuclear medicine, and 80 are members of at least one professional society or association. This amounts to 3.3 memberships per person. 43 respondents are or have been involved in the clinical guideline development by the DGN or by other medical disciplines. In the future more than half of these persons are willing to participate in the guideline development furthermore. 13 colleagues have participated in the 30 reviews or official hearings concerning the clinical evidence evaluation of PET/CT by the German Institute for Quality and Efficiency in Health Care (IQWiG) (effective date: January 15, 2012). 21 (18.8%) persons are members of 23 federal, governmental or other political boards with relevance for research. 38 persons (33.9%) are committed to professional self-governmental bodies. 14 colleagues stated that they support the work of patient interest groups or other non-profit organisations as consultants or advisors. In most cases, this work is related to the patient interest group "Living without Thyroid". 14 colleagues report special experiences or knowledge that could be helpful for our DGN working groups. In the same manner, good contacts to government departments and agencies or representatives of politics and economy (stated by 24 respondents) can be of advantage to further shape the DGN's professional profile in the German health care sector. CONCLUSION: As the result of a continuously advanced professionalization (2), the DGN has a good infrastructure concerning the political and professional work of its boards (executive committee and working groups). The operational and administrative work of the society and its boards is carried out or coordinated entirely by the society's office. Especially the development of the professional potential within the DGN by increasingly involving leaders working in clinical routine or research is the basis for the future of nuclear medicine.

Automatic volume delineation in oncological PET. Evaluation of a dedicated software tool and comparison with manual delineation in clinical data sets.

AIM: Evaluation of a dedicated software tool for automatic delineation of 3D regions of interest in oncological PET. PATIENTS, METHODS: The applied procedure encompasses segmentation of user-specified subvolumes within the tomographic data set into separate 3D ROIs, automatic background determination, and local adaptive thresholding of the background corrected data. Background correction and adaptive thresholding are combined in an iterative algorithm. Nine experienced observers used this algorithm for automatic delineation of a total of 37 ROIs in 14 patients. Additionally, the observers delineated the same ROIs also manually (using a freely chosen threshold for each ROI) and the results of automatic and manual ROI delineation were compared. RESULTS: For the investigated 37 ROIs the manual delineation shows a strong interobserver variability of (26.8±6.3)% (range: 15% to 45%) while the corresponding value for automatic delineation is (1.1±1.0)% (range: <0.1% to 3.6%). The fractional deviation of the automatic volumes from the observer-averaged manual ones is (3.7±12.7)%. CONCLUSION: The evaluated software provides results in very good agreement with observer-averaged manual evaluations, facilitates and accelerates the volumetric evaluation, eliminates the problem of interobserver variability and appears to be a useful tool for volumetric evaluation of oncological PET in clinical routine.

[Biological aspects of radiation in nuclear medicine]. / Strahlenbiologie. Sicht der Nuklearmedizin.

Radiotherapy with unsealed radionuclides differs from external radiotherapy with regard to the radiation quality and energy range, the regional dose uniformity and the time course of irradiation regimen. External radiotherapy is planned precisely and can be applied to a target volume independently from blood flow during a course of irradiation fractions. In contrary, administered radiopharmaceuticals distribute according to their pharmacokinetic properties and generate a continuous irradiation corresponding to the effective halflife. The resulting dose rates are approximately 1Gy/min and 1Gy/h, respectively. The biokinetics of radiopharmaceuticals involves cellular accumulation and retention with highly variable affinity to specific organs that can be modulated as well. A remarkable dose gradient is found at the edge of volumes with enhanced uptake. The biological effect of an irradiation with decreasing intensity can be compared with the radiation effect caused by conventional fractionation with 2 Gy a day in external beam therapy by means of the linear-quadratic model. However, the experimental validation of this translation is still under investigation. Radionuclide therapy is usually performed in several cycles some month apart. This procedure fails to meet external radiotherapy. The vision of a combined external-internal radiotherapy requires efforts for a common dosimetry approach both in vitro and in vivo with a physical and biological verification of the results.

[Positron emission tomography 2008 in Germany - results of the query and current status]. / Positronenemissionstomographie 2008 in Deutschland - Ergebnisse der Erhebung und Standortbestimmung.

AIM: The working group on positron emission tomography (PET) of the DGN (German Society of Nuclear Medicine) initiated this first survey to collect and analyse information on the practise of PET in Germany in the year 2008. METHODS: A questionnaire was sent to PET performing facilities (medical practices, hospitals, university hospitals and others) for retrospective data acquisition. Details regarding the equipment and examination procedures were examined as well as indications and number of studies. In addition, the role of PET within the diagnostic process was evaluated. RESULTS: Responses from 65 sites were analysed. Their technical equipment consisted of 77 PET scanners (40 of them were combined PET/CT devices). About 63500 PET studies had been performed with 86% in the field of oncology, 8% in neurology and 3% in cardiology. The radiotracers were labelled with 18F in 91% of the studies, whereas 68Ga was used in 4% and 11C in 3%. The analyses revealed lung tumours as the most investigated tumour entity, followed by malignant lymphoma, tumours of the gastro-intestinal tract and prostate cancer (about 14000, 6000, 5000 and 2000). Corresponding to the new scanners and software procedures, the number of studies with attenuation correction by CT was high (68%) and nearly all studies were reconstructed iteratively (99%). The PET images were analysed quantitatively in the majority of cases (91%). The clinical reports, which included image documentation for the greater part, were posted regularly within 3 days. However, in 70% of the sites electronic transfer possibilities were used additionally to speed up the diagnostic process. The high standard of quality was demonstrated by the fact, that 40 facilities were engaged in a tumour board. Further on, one third of the physicians had gained a PET certification awarded by the DGN. CONCLUSION: Relative to the high general standard of diagnostic instrumentation in Germany, PET is less established, in particular when compared with other industrialised countries such as USA and Switzerland.

[Radiation exposure of patients during 68Ga-DOTATOC PET/CT examinations]. / Strahlenexposition der Patienten bei Untersuchungen mit 68Ga-DOTATOC am PET/CT.

AIM: Investigation of the biodistribution and calculation of dosimetry of Ga-68-DOTATOC- for patients imaged in the routine clinical setting for diagnosis or exclusion of neuroendocrine tumours. PATIENTS, METHODS: Dynamic PET/CT-imaging (Biograph 16) was performed over 20 min in 14 patients (8 men, 6 women) after injection of (112+/-22) MBq 68Ga-DOTATOC followed by whole body 3D-acquisition (8 bed positions, 3 or 4 min each) 30 min p.i. and 120 min p.i.. Urinary tracer elimination was measured and blood activity was derived non-invasively from the blood pool of the heart. The relevant organs for dosimetry were spleen, kidneys, liver, adrenals, urinary bladder and pituitary gland. Dosimetry was performed using OLINDA/EXM 1.0 software and specific organ uptake was expressed as standardized uptake values (SUVs). RESULTS: Rapid physiological uptake of the radiotracer could be demonstrated in liver, spleen and kidneys, adrenals and pituitary gland (mean SUVs were 6, 20, 16, 10, and 4, respectively). Radiotracer elimination was exclusively via urine (16% of injected dose within 2h); no redistribution could be observed. The spleen and the kidneys received the highest radiation exposure (0.24 mSv/MBq, 0.22 mSv/MBq resp.), mean effective dose yielded 0.023 mSv/MBq. CONCLUSION: 68Ga-DOTATOC is used extensively for diagnosis of somatostatin receptor positive tumours because it has several advantages over the 111In-labelled ligand. The derived dosimetric values are lower than first approximations from the biological data of OctreoScan. The use of CT for transmission correction of the PET data delivers radiation exposure up to 1 mSv (low dose).

Radiation treatment planning in brain tumours: potential impact of 3-O-methyl-6-[(18)F]fluoro-L-DOPA and PET.

AIM: Amino acid PET has become an important diagnostic tool for brain tumour imaging. In this data analysis, the potential impact of amino acid PET with 3-O-methyl-6-[(18)F]fluoro-L-DOPA ([(18)F]OMFD) on radiation treatment planning is addressed by the following questions: 1. Was tumour tissue identified with OMFD-PET which was not covered by the conventionally derived planning target volume (PTV)? 2. Would the PTV have been changed incorporating OMFD-PET? PATIENTS, METHODS: OMFD-PET of 25 patients after subtotal resection of malignant glioma was evaluated. The region of elevated tracer uptake of PET and of contrast enhancing masses on MRI were outlined as separate gross tumour volumes (GTV(MRI) and GTV(OMFD)) and reconstructed in the planning CT for comparison with the conventionally drawn GTV(conv). A PTV(new) based on GTV(conv+MRI) was calculated. Pairwise differential volumes were calculated to estimate overlap and differential volumes delineation by each image modality and the PTV(conv) and PTV(new) respectively. RESULTS: Differential volume analysis showed > 10 cm(3) of GTV(OMFD) outside GTV(conv) and GTV(MRI) in 5/25 patients respectively. From GTV(MRI) > 10 cm(3) were found outside GTV(OMFD) in 8/25 patients. Although all tumour areas indicated by [(18)F]OMFD were covered by the conventionally derived PTV, based on a GTV(OMFD+MRI), the PTV(new) would have been enlarged >20% in seven patients. In seven patients the PTV(new) would have been reduced. CONCLUSION: OMFD-PET indicated tumour tissue outside the tumour region identified with MRI, adding valuable information for the delineation of the GTV in radiation treatment planning. OMFD-PET contains the potential to tailor the high dose radiation to the appropriate tumour volume, especially if dose escalation is desired.

[Influence of time-dose-relationships in therapeutic nuclear medicine applications on biological effectiveness of irradiation: consequences for dosimetry]. / Einfluss der Dosisleistung nuklearmedizinischer Therapie auf die biologische Strahlenwirkung. Konsequenzen für die Dosimetrie.

AIM: The biological effectiveness of irradiation is influenced not only by the total dose but also the rate at which this dose is administered. Tolerance dose estimates from external radiation therapy with a conventional fractionation protocol require adaptation for application in targeted radionuclide therapy. METHODS: The linear-quadratic model allows for calculation of the biologically effective dose (BED) and takes into consideration tissue specific factors (recovery capacity) as well as dose rate effects (recovery kinetics). It can be applied in radionuclide therapy as well. For relevant therapeutic radionuclides (e. g. (188)Re, (90)Y, (177)Lu, and (131)I), the effect of different physical decay times and variable biological half-lives on BED was calculated for several organs. RESULTS: BED is markedly increased using (188)Re compared to longer-lived radionuclides. The effect is dose-dependent and tissue-specific, resulting, for example, in higher effects on the kidneys compared to bone marrow. Therefore, in unfavourable conditions (e. g. reduced recovery capacity due to concomitant diseases or previous therapy), the BED may exceed organ dose tolerance. CONCLUSION: Time-dose-relationships have to be taken into consideration by the calculation of BED for internal radionuclide therapy. The biological effectiveness depends on dose- and tissue-specific factors and is much more pronounced in (188)Re than in (90)Y and other longer living radionuclides. Determination of organ tolerance dose values should take into account these radiobiological differences, since it is currently not considered in dosimetry programs.

Persistent vegetative state: evaluation of brain metabolism and brain perfusion with PET and SPECT.

Patients in persistent vegetative state (PVS) after severe head trauma were investigated with 99mTc-ECD SPECT and 18F-FDG PET to further characterize the degree of brain damage and to obtain insight into changes of brain perfusion and glucose metabolism. 18F-FDG PET and 99mTc-ECD SPECT were performed in 16 patients in PVS. Quantitative PET data were compared with that obtained from seven normal controls. After spatial normalization into Talairach space, global grey matter values and regional data using predefined ROI sets were derived. For comparison of PET and SPECT, regional data were normalized to their individual mean grey matter values. Patients in PVS showed significantly lower values of cerebral glucose metabolism than did the controls. The mean reduction of grey matter values in cortical and subcortical structures was 58%, except in the vermis cerebelli, where only a reduction of 16% was found compared to the controls. Comparing the glucose metabolism and perfusion within the patient group, the pattern of both modalities was similar in the neocortex and internal ganglia. In the cerebellar hemispheres a relatively higher perfusion than glucose metabolism was found. The overall reduction of 58% of glucose metabolism in grey matter structures is in accordance with other PET studies investigating PVS patients with different disease histories. The relative preserved activity of vermis cerebelli seems to be an uncommon finding not described by other authors up to now.

[Changes in regional cerebral perfusion in depression.SPECT monitoring of response to treatment]. / Regionale Funktionsstörung bei der Depression. Hirn-SPECT zur Verlaufskontrolle.

The objective of this study was to investigate the relationship between the effect of sleep deprivation, recovery and regional brain perfusion in patients with major depression. Regional cerebral blood flow was assessed by 99mTc-HMPAO-SPECT before and after sleep deprivation in fourteen medicated patients. Three of the patients underwent a follow-up measurement after clinical recovery and with an unchanged antidepressant medication. Before sleep deprivation the responding patients had a significantly higher anterior cingulate perfusion than the nonresponding patients, that normalized after sleep deprivation. Cingulate perfusion uniquely differentiated eventual treatment response from non-responders, as perfusion in no other region under study discriminated the two groups. At baseline all patients revealed hypoperfusion in the left prefrontal cortex when compared to the right side, which was not affected by sleep deprivation, whereas prefrontal hypoperfusion was reversible upon remission. These findings are in agreement with previous PET investigations and provide evidence for cingulate and prefrontal dysfunction associated with depression, that are reversible by successful treatment and may represent state markers.