Abstract Background Approaches targeting the sodium-glucose cotransporter (SGLT) could represent a promising future therapeutic strategy for numerous oncological and metabolic diseases. In this study, we evaluated the safety, biodistribution and radiation dosimetry of the glucose analogue positron emission tomography (PET) agent [18F] labeled alpha-methyl-4-deoxy-4-[18F]fluoro-D-glucopyranoside ([18F]Me4FDG) with high sodium-glucose cotransporter and low glucose transporter (GLUT) affinity. For this purpose, five healthy volunteers (1 man, 4 women) underwent multiple whole-body PET/computed tomography (CT) examinations starting with injection and up to 4 h after injection of averaged (2.4 ± 0.1) MBq/kg (range: 2.3–2.5 MBq/kg) administered activity. The PET/CT scans were conducted in 5 separate sessions, blood pressure and temperature were measured, and blood and urine samples were collected before the scans and one hour after injection to assess toxicity. Measurements of [18F]Me4FDG radioactivity in organs of interest were determined from the PET/CT scans at 5 time points. Internal dosimetry was performed on voxel level using a fast Monte Carlo approach. Results All studied volunteers could well tolerate the [18F]Me4FDG and no adverse event was reported. The calculated effective dose was (0.013 ± 0.003) mSv/MBq. The organs with the highest absorbed dose were the kidneys with 0.05 mSv/MBq per kidney. The brain showed almost no uptake. After 60 min, (12 ± 15) % of the administered dose was excreted into the bladder. Conclusion Featuring an effective dose of only 0.013 ± 0.003 mSv/MBq and no occurrence of side effects, the glucose analogue [18F]Me4FDG seems to be a safe radio-tracer with a favorable biodistribution for PET imaging and also within several consecutive scans. Trial registration number NCT03557138, Registered 22 February 2017, https://ichgcp.net/clinical-trials-registry/NCT03557138.

Purpose Long axial field-of-view (LAFOV) positron emission tomography (PET) systems allow to image all major organs with one bed position, which is particularly useful for acquiring whole-body dynamic data using short-lived radioisotopes like 82 Rb. Methods We determined the absorbed dose in target organs of three subjects (29, 40, and 57 years old) using two different methods, i.e., MIRD and voxel dosimetry. The subjects were injected with 407.0 to 419.61 MBq of [ 82 Rb]Cl and were scanned dynamically for 7 min with a LAFOV PET/CT scanner. Results Using the MIRD formalism and voxel dosimetry, the absorbed dose ranged from 1.84 to 2.78 μGy/MBq (1.57 to 3.92 μGy/MBq for voxel dosimetry) for the heart wall, 2.76 to 5.73 μGy/MBq (3.22 to 5.37 μGy/MBq for voxel dosimetry) for the kidneys, and 0.94 to 1.88 μGy/MBq (0.98 to 1.92 μGy/MBq for voxel dosimetry) for the lungs. The total body effective dose lied between 0.50 and 0.76 μSv/MBq. Conclusion Our study suggests that the radiation dose associated with [ 82 Rb]Cl PET/CT can be assessed by means of dynamic LAFOV PET and that it is lower compared to literature values.

Purpose Amyloid positron emission tomography (PET) with [ 18 F]florbetaben (FBB) is an established tool for detecting Aβ deposition in the brain in vivo based on visual assessment of PET scans. Quantitative measures are commonly used in the research context and allow continuous measurement of amyloid burden. The aim of this study was to demonstrate the robustness of FBB PET quantification. Methods This is a retrospective analysis of FBB PET images from 589 subjects. PET scans were quantified with 15 analytical methods using nine software packages (MIMneuro, Hermes BRASS, Neurocloud, Neurology Toolkit, statistical parametric mapping (SPM8), PMOD Neuro, CapAIBL, non-negative matrix factorization (NMF), Amyloid IQ ) that used several metrics to estimate Aβ load (SUVR, centiloid, amyloid load, and amyloid index). Six analytical methods reported centiloid (MIMneuro, standard centiloid, Neurology Toolkit, SPM8 (PET only), CapAIBL, NMF). All results were quality controlled. Results The mean sensitivity, specificity, and accuracy were 96.1 ± 1.6%, 96.9 ± 1.0%, and 96.4 ± 1.1%, respectively, for all quantitative methods tested when compared to histopathology, where available. The mean percentage of agreement between binary quantitative assessment across all 15 methods and visual majority assessment was 92.4 ± 1.5%. Assessments of reliability, correlation analyses, and comparisons across software packages showed excellent performance and consistent results between analytical methods. Conclusion This study demonstrated that quantitative methods using both CE marked software and other widely available processing tools provided comparable results to visual assessments of FBB PET scans. Software quantification methods, such as centiloid analysis, can complement visual assessment of FBB PET images and could be used in the future for identification of early amyloid deposition, monitoring disease progression and treatment effectiveness.

Purpose: Selective internal radiation therapy (SIRT) is a treatment for various kinds of liver tumours by injecting Y-90 bearing microspheres into the liver vessels. To perform meaningful post-treatment dosimetry, quantitative imaging is performed. Methods: This work uses a Monte-Carlo based reconstruction software with scatter and attenuation correction and collimator modelling that allows the quantification of 90Y bremsstrahlung SPECT/CT data. A dataset comprising 17 patients and measurements on a Jaszczak phantom, a NEMA IEC Body phantom and an anthropomorphic liver phantom are analysed and activities and dose values are acquired. These measured values are compared with applied activities and pre-treatment calculations, allowing to assess the quality of the SPECT reconstruction. A detailed uncertainty budget is presented, including uncertainties of the dose calibrator, the count rate, non-included interactions and other factors. Results: The applied method is validated by finding measurements repeatable within the given uncertainty, and it is shown the influence of various parameters on the reconstruction process is negligible. Furthermore, activities and doses measured in the phantoms show good agreement with calculated values, if they are corrected for partial volume effects. Conclusions: The strict observation of metrological requirements and the creation of an uncertainty budget increase the reliability and traceability of this novel approach to Y-90 dosimetry. It gives an example of successful voxel-based dosimetry based on quantitative Y-90 SPECT/CT image data.

Even though [123I]FP-CIT SPECT provides high accuracy in detecting nigrostriatal cell loss in neurodegenerative parkinsonian syndromes (PS), some patients with an inconclusive diagnosis remain. We investigated whether the diagnostic accuracy in patients with clinically uncertain PS with previously inconclusive findings can be improved by the use of iterative reconstruction algorithms and an improved semiquantitative evaluation which additionally implemented a correction algorithm for patient age and gamma camera dependency (EARL-BRASS; Hermes Medical Solutions, Sweden).

Objective: To evaluate a home-built Java-based program (GFRcalc) to simplify the calculation of glomerular filtration rate (GFR) after administration of chromium-51 ethylenediaminetetraacetic acid (51Cr-EDTA) for routine clinical use. Materials and Methods: In the program GFRcalc, the GFR was calculated based on the biological half-life of the 51Cr-EDTA concentration using the slope-intercept method of between two and five blood samples. Additional features included the ability to export patient data and generate clinical reports as well as to calculate the error of the fit of the GFR measurement in cases with three or more blood samples collected. The GFR was calculated from one, two and three blood samples of 133 patients with body surface-corrected GFR of 21-213 ml/min/1.73 m2. The Pearson correlation coefficient and the error of the fit for the GFR measurement were calculated for the three-sample method. Results: The correlation coefficient for the three-sample method and the fit error correlated well for small fit errors; in case of fit errors >10%, the correlation coefficient partially differed in results compared to the other methods. The three-sample GFR values differed by approximately 17% from the single-sample GFRs. The fit errors of the three-sample GFRs correlated (r = 0.57) with their difference from the two-sample GFRs. Conclusion: In this study, the fit error that GFRcalc provided for the three-sample GFR offered a simple and reliable method to check the results obtained. This could also allow physicians to assess the reliability of the results and base their decisions on the quality of the measurement.

Apart from binding to the dopamine transporter (DAT), [123I]FP-CIT shows moderate affinity for the serotonin transporter (SERT), allowing imaging of both monoamine transporters in a single imaging session in different brain areas. The aim of this study was to systematically evaluate extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls.

Background Internal dose assessment after radionuclide therapy is usually performed using home-made software packages. The dose assessment includes image registration, region-of-interest drawing, time-activity curve generation, and manual calculation of residence times followed by dose calculation with the OLINDA/MIRD software. The drawback of these methods is that several steps have to be performed using various software products possibly installed on different workstations. The aforementioned approaches are error-prone as well as difficult and time-consuming. In this article, we present a commercial software package that implements all the required dose calculation steps in 1 application, which greatly facilitates the internal dose assessment. Methods and Results The workflow of the newly developed software package “Hybrid Dosimetry” proceeds from automatic image registration to region-of-interest drawing, followed by time-activity curve fitting and dose calculation according to the MIRD method. The software is available online and can be run on independent computers using images in the common DICOM format. We used the package for internal dosimetry of 8 patients treated with 177Lu-DOTATATE and compared the results with manual dose calculation. Conclusions The online software package presented is platform independent and allows fast dose calculations. The results obtained with the new package were in perfect agreement with manual methods.

BACKGROUND:Experimental models are essential tools in the development and evaluation of novel treatment options, but the preclinical model of renal ischemia-reperfusion injury is limited to the retrieval of (very) early functional data, leaving the pivotal long-term outcome unknown. The present study applies technetium-99m-mercapto-acetyl-tri-glycine [99mTc-MAG3] scintigraphy for the longitudinal follow-up examination of long-term kidney function after renal ischemia-reperfusion injury.METHODS:Unilateral warm ischemia was induced in scid beige mice by vascular clamping of the kidney hilum for 40 min. 99mTc-MAG3 scintigraphy was performed prior to injury, 8 and 14 days post ischemia. The fractional uptake rate [FUR] was calculated from scintigraphy data as a measure of renal clearance.RESULTS:FUR demonstrated a significant functional impairment of the ischemic kidney 8 and 14 days after injury (P < 0.05 vs. baseline), while contralateral non-ischemic kidneys showed no significant changes. In histological analysis, ischemic kidneys exhibited tubular dilatation and cytoplasmic degeneration as signs of hypoxia without any evidence for necrosis.CONCLUSIONS:FUR enables the detection of renal dysfunction and longitudinal long-term follow-up examination in the same individual. Our model may facilitate preclinical therapy evaluation for the identification of effective renoprotective therapies.

Florbetaben is a promising beta-amyloid-targeted PET tracer currently in global clinical development. In the beta-amyloid PET community there is a growing understanding that standardization of image data analysis is of importance. For florbetaben PET, in addition to visual scan interpretation, quantification via standardized uptake value ratios (SUVRs) and total brain volume affected by beta-amyloid may be of significant value. In a recent pilot trial, we identified the HERMES BRASS module as a potential tool to operator-independently determine both of these quantitative parameters. In this present work we evaluated the diagnostic performance of this tool when analyzing multi-center data. A BRASS database was generated from florbetaben PET scans of 93 cognitively normal, beta-amyloid-negative healthy volunteers (HVs). Using this normal database, 145 florbetaben PET scans (77 patients with probable AD, 68 HVs) obtained from the multi-center Phase 2 trial were analyzed. For that purpose, the datasets were compared with the normal database in a voxel-based and volume of interest (VOI)-based manner. The VOI analysis resulted in composite SUVRs which were compared to those obtained by a reference technique (grey matter vs. white matter / CSF segmentation on individual MRIs, VOIs from modified AAL template). The BRASS analysis of the florbetaben datasets was possible without operator-interventions within 41 ± 4 sec. The composite SUVRs as determined by BRASS correlated significantly with those determined by the reference method (r = 0.85, p < 0.001). Also, the composite SUVRs obtained with BRASS and the reference approach discriminated equally well between ADs and HVs (p < 0.001, Cohen's d = 1.37 for both approaches). In the ADs and HVs, 3.2 ± 2.7 vs. 0.1 ± 0.4 (p < 0.001, Cohen's d = 1.61) neocortical regions were defined by BRASS as pathologic (z-score > 2.5). The total brain volume affected by beta-amyloid was 18.6 ± 25.7 vs. 0.8 ± 3.7ml for the ADs and HVs (p < 0.001). The BRASS tool customized for florbetaben PET demonstrated excellent ability in discriminating between ADs and HVs, both on a regional and a voxel-based level. Thus, this software has great potential in supporting the visual interpretation of florbetaben PET image data in a rapid, user friendly and operator-independent manner.

1254 Objectives For β-amyloid brain PET with florbetaben, in addition to visual scan interpretation quantification via standardized uptake value ratios (SUVRs) and total brain volume affected may be of significant value. In a recent pilot trial, we identified the Hermes BRASS module as a potential tool to operator-independently determine both of these quantitative parameters. In this present work we evaluated the diagnostic performance of this tool when analyzing multi-center data. Methods BRASS database generation: Florbetaben PET scans from 93 cognitively normal, β-amyloid-negative healthy volunteers (HVs). Database testing: 145 florbetaben PET scans (77 patients with probable AD, 68 HVs) obtained from a multi-center Phase 2 trial, individual voxelwise and VOI-based comparison with normal database, composite SUVRs obtained by BRASS compared to those obtained by reference technique (grey matter segmentation on individual MRIs, VOIs from modified AAL template). Results The BRASS analysis of the florbetaben datasets was possible without operator-interventions within 41±4 sec. The composite SUVRs in ADs as determined by BRASS correlated significantly with those determined by the reference method (r=0.80, p 2.5). The total brain volume affected by β-amyloid was 18.6±25.7 vs. 0.8±3.7ml for the ADs and HVs (p Conclusions Florbetaben BRASS demonstrated excellent ability in discriminating between ADs and HVs, both on a regional and a voxel-based level. Thus, this software has great potential in supporting the visual interpretation of florbetaben PET image data in a rapid, user friendly and operator-independent manner. Research Support Bayer Healthcare, Berlin (Germany

Background The concept of acupuncture point localisation in Traditional Chinese Medicine (TCM) is based on millenary practical experience. Modern imaging methods such as PET, MRI and SPECT have been used primary for the investigation of the mechanisms of action of acupuncture. In this pilot single-case study we have evaluated the technical possibilities for in-vivo imaging of the anatomical relations of acupuncture points using state of the art MRI. Methods Preliminary experiments relating to the quality of acupuncture needles under the setting of MRI were done both with stainless steel and gold needles. In a second step, in-vivo imaging was carried out. A licensed acupuncture practitioner (RM) chose two points belonging to the so-called extraordinary vessels. In 2 sequential, separate procedures, he inserted himself gold acupuncture needles using a neutral technique (known as Ping Bu Ping Xie) into the Dai mai and Shen mai points, i.e. gall bladder 26 and bladder 62. Imaging was done on a Siemens Magnetom Avanto MR scanner using a head array and body coil. Mainly T1-weighted imaging sequences, as routinely used for patient exams, were used to obtain multi-slice images. Results In the preliminary experiments only acupuncture needles made of gold showed enough stability in order to be used for further imaging procedures. Using an onion and a banana as an object, further studies showed that the gold needles produced a void defect that corresponds to the tip of the inserted needle, while at the same time an artefactually increased diameter was observed. The in-vivo experiments showed that the Dai mai point was in relation to the abdominal internal oblique muscle. The Shen mai point artefact showed up close to the longus and brevis peroneal tendons at the fibular malleolus. Side effects related to heating or burning were not observed. Improved anatomical recognition was obtained using 3D-volume rendering techniques. Conclusion Through an adequate choice of acupuncture material (gold needles) as well as of ideal MRI imaging sequences it has been possible to visualize the anatomical characteristics at the acupuncture points Dai mai and Shen mai in-vivo. At the selected sites the needles showed a relation to tendino-fascial and muscular structures. These anatomical structures fit well into the recently described WOMED concept of lateral tension in which these acupuncture points play a regulatory role.

123I-ADAM ist ein neuer Radioligand fur die bildgebende Diagnostik der zerebralen Serotonintransporter (SERTs). Bisher beruhte die Analyse zerebraler Rezeptorstudien auf der Beobachter-abhangigen Definition der Bereiche besonderen Interesses und der visuellen Interpretation. Unser Ziel war, eine Schablone fur automatische Bilddeckungen und fur Quantifizierungen des interessierenden Volumens (VOI) zu erstellen und zu zeigen, dass eine automatische Methode zur Quantifizierung von 123I-ADAM reproduzierbarer ist als die manuelle Methode. Patienten, Methoden: Aus 123I-ADAM-Scans, die bei Gesunden durchgefuhrt wurden (n = 15), wurden eine Schablone und eine vordefinierte VOI-Karte erstellt. Scans einer anderen Gruppe Gesunder (GP, n = 12) und von Patienten mit Bulimia nervosa (BN, n = 10) wurden automatisch in die Schablone eingepasst, und es wurden spezielle Bindungsquotienten (specific binding ratios – SBRs) unter Verwendung der VOIKarte berechnet. Die manuellen VOI-Definitionen wurden fur die GP- und BN-Gruppe sowohl von einem als auch von zwei Beobachtern vorgenommen. Die Reproduzierbarkeit der automatischen Methode wurde anhand der BN-Gruppe ausgewertet. Ergebnisse: Bei der manuellen Methode betrug der Interbeobachter-Koeffizient der Reproduzierbarkeit bei der GP-Gruppe 0,61 und bei der BN-Gruppe 1,00. Der Intrabeobachter-Koeffizient der Reproduzierbarkeit fur die BN-Gruppe betrug 0,70. Bei der automatischen Methode betrug der Koeffizient der Reproduzierbarkeit fur die SBRs im Mittelhirn 0,13. Schlussfolgerung: Eine automatische Quantifizierung liefert zusatzlich zur visuellen Interpretation wertvolle Informationen und verkurzt gleichzeitig die Gesamt-Bildbearbeitungszeit und bietet eindeutige Vorteile fur wissenschaftliche Arbeiten. Eine automatische Methode fur die Analyse der 123I-ADAM-Bindung an den zerebralen SERT liefert reproduzierbare Ergebnisse fur die Einpassung der Studien in die Schablone und fur die Berechnung der SBRs; sie konnte manuelle Methoden ersetzen.

Summary: 123I-ADAM is a novel radioligand for imaging of the brain serotonin transporters (SERTs). Traditionally, the analysis of brain receptor studies has been based on observer-dependent manual region of interest definitions and visual interpretation. Our aim was to create a template for automated image registrations and volume of interest (VOI) quantifications and to show that an automated quantification method of 123I-ADAM is more repeatable than the manual method. Patients, methods: A template and a predefined VOI map was created from 123I-ADAM scans done for healthy volunteers (n = 15). Scans of another group of healthy persons (HS, n = 12) and patients with bulimia nervosa (BN, n = 10) were automatically fitted to the template and specific binding ratios (SBRs) were calculated by using the VOI map. Manual VOI definitions were done for the HS and BN groups by both one and two observers. The repeatability of the automated method was evaluated by using the BN group. Results: For the manual method, the interobserver coefficient of repeatability was 0.61 for the HS group and 1.00 for the BN group. The intraobserver coefficient of repeatability for the BN group was 0.70. For the automated method, the coefficient of repeatability was 0.13 for SBRs in midbrain. Conclusion: An automated quantification gives valuable information in addition to visual interpretation decreasing also the total image handling time and giving clear advantages for research work. An automated method for analysing 123I-ADAM binding to the brain SERT gives repeatable results for fitting the studies to the template and for calculating SBRs, and could therefore replace manual methods.