Effects of isoflurane anaesthesia depth and duration on renal function measured with [99mTc]Tc-mercaptoacetyltriglycine SPECT in mice.

BACKGROUND: The influence of anaesthetic depth and the potential influence of different anaesthetic beds and thus different handling procedures were investigated in 86 severe combined immunodeficient (SCID) mice using semi-stationary dynamic single photon emission computed tomography (SPECT) for kidney scintigraphy. Therefore, isoflurane concentrations were adjusted using respiratory rate for low (80-90 breath/min) and deep anaesthesia (40-45 breath/min). At low anaesthesia, we additionally tested the influence of single bed versus 3-mouse bed hotel; the hotel mice were anaesthetized consecutively at ~ 30, 20, and 10 min before tracer injections for positions 1, 2, and 3, respectively. Intravenous [99mTc]Tc-MAG3 injection of ~ 28 MBq was performed after SPECT start. Time-activity curves were used to calculate time-to-peak (Tmax), T50 (50% clearance) and T25 (75% clearance). RESULTS: Low and deep anaesthesia corresponded to median isoflurane concentrations of 1.3% and 1.5%, respectively, with no significant differences in heart rate (p = 0.74). Low anaesthesia resulted in shorter aortic blood clearance half-life (p = 0.091) and increased relative renal tracer influx rate (p = 0.018). A tendency toward earlier Tmax occurred under low anaesthesia (p = 0.063) with no differences in T50 (p = 0.40) and T25 (p = 0.24). Variance increased with deep anaesthesia. Compared to single mouse scans, hotel mice in position 1 showed a delayed Tmax, T50, and T25 (p < 0.05 each). Furthermore, hotel mice in position 1 showed delayed Tmax versus position 3, and delayed T50 and T25 versus position 2 and 3 (p < 0.05 each). No difference occurred between single bed and positions 2 (p = 1.0) and 3 (p = 1.0). CONCLUSIONS: Deep anaesthesia and prolonged low anaesthesia should be avoided during renal scintigraphy because they result in prolonged blood clearance half-life, delayed renal influx and/or later Tmax. Vice versa, low anaesthesia with high respiratory rates of 80-90 rpm and short duration (≤ 20 min) should be preferred to obtain representative data with low variance.

Predictive factors for the outcome of radioiodine therapy in patients with benign thyroid diseases.

PURPOSE: Radioiodine therapy (RIT) of benign thyroid diseases is an established therapy. This study aimed to identify factors predictive for outcome in patients with non-toxic goiter (NTG), unifocal (UFA), multifocal (MUFA) or diffuse autonomy (DISA) and Graves' disease (GD). METHODS: Retrospective analysis of 205 patients with benign thyroid disease (54 NTG, 46 MUFA, 24 DISA, 26 UFA, 55 GD) who underwent RIT. Follow up time was 12 months for determining treatment outcome. RESULTS: The type of disease was predictive for volume reduction after 12 months (NTS 66%, DISA 67%, MUFA 58%, UFA 51%, GD 71%, p<0.001) and post-treatment hypothyroidism (NTS 48%, DISA 33%, MUFA 15%, UFA 15%, p=0.006). Initial volume, intra-therapeutic uptake and intra-therapeutic half-life were independent prognostic factors for volume reduction 12 months after RIT. In patients with NTG, UFA, MUFA, DISA post-treatment hypothyroidism was significantly correlated with extent of volume reduction 12 months after RIT, achieved dose, higher pre-therapeutic TSH values and younger age. Two different strategies for pre-therapeutic dosimetry used in MUFA showed no differences regarding the therapeutic outcome. In GD, effective half-life, initial volume and Graves' ophthalmopathy were predictive for treatment failure. CONCLUSION: Reduction of thyroid volume and the percentage of hypothyroid patients one year after RIT was primarily dependent on the type of disease. In MUFA and DISA we could identify volume reduction after 3 months as a reliable predictor for hypothyroidism while in patients with GD a short intra-therapeutic half-life, a large pre-therapeutic volume and active Graves' ophtalmopathy were relevant predictors for treatment failure suggesting an intensified follow-up scheme in these patients.

Detection of recurrent high-grade glioma using microstructure characteristics of distinct metabolic compartments in a multimodal and integrative 18F-FET PET/fast-DKI approach.

OBJECTIVES: Differentiation between high-grade glioma (HGG) and post-treatment-related effects (PTRE) is challenging, but advanced imaging techniques were shown to provide benefit. We aim to investigate microstructure characteristics of metabolic compartments identified from amino acid PET and to evaluate the diagnostic potential of this multimodal and integrative O-(2-18F-fluoroethyl)-L-tyrosine-(FET)-PET and fast diffusion kurtosis imaging (DKI) approach for the detection of recurrence and IDH genotyping. METHODS: Fifty-nine participants with neuropathologically confirmed recurrent HGG (n = 39) or PTRE (n = 20) were investigated using static 18F-FET PET and a fast-DKI variant. PET and advanced diffusion metrics of metabolically defined (80-100% and 60-75% areas of 18F-FET uptake) compartments were assessed. Comparative analysis was performed using Mann-Whitney U tests with Holm-Sídák multiple-comparison test and Wilcoxon signed-rank test. Receiver operating characteristic (ROC) curves, regression, and Spearman's correlation analysis were used for statistical evaluations. RESULTS: Compared to PTRE, recurrent HGG presented increased 18F-FET uptake and diffusivity (MD60), but lower (relative) mean kurtosis tensor (rMKT60) and fractional anisotropy (FA60) (respectively p < .05). Diffusion metrics determined from the metabolic periphery showed improved diagnostic performance - most pronounced for FA60 (AUC = 0.86, p < .001), which presented similar benefit to 18F-FET PET (AUC = 0.86, p < .001) and was negatively correlated with amino acid uptake (rs = - 0.46, p < .001). When PET and DKI metrics were evaluated in a multimodal biparametric approach, TBRmax + FA60 showed highest diagnostic accuracy (AUC = 0.93, p < .001), which improved the detection of relapse compared to PET alone (difference in AUC = 0.069, p = .04). FA60 and MD60 distinguished the IDH genotype in the post-treatment setting. CONCLUSION: Detection of glioma recurrence benefits from a multimodal and integrative PET/DKI approach, which presented significant diagnostic advantage to the assessment based on PET alone. CLINICAL RELEVANCE STATEMENT: A multimodal and integrative 18F-FET PET/fast-DKI approach for the non-invasive microstructural characterization of metabolic compartments provided improved diagnostic capability for differentiation between recurrent glioma and post-treatment-related changes, suggesting a role for the diagnostic workup of patients in post-treatment settings. KEY POINTS: • Multimodal PET/MRI with integrative analysis of 18F-FET PET and fast-DKI presents clinical benefit for the assessment of CNS cancer, particularly for the detection of recurrent high-grade glioma. • Microstructure markers of the metabolic periphery yielded biologically pertinent estimates characterising the tumour microenvironment, and, thereby, presented improved diagnostic accuracy with similar accuracy to amino acid PET. • Combined 18F-FET PET/fast-DKI achieved the best diagnostic performance for detection of high-grade glioma relapse with significant benefit to the assessment based on PET alone.

Metallacages with 2,6-dipicolinoylbis(N,N-dialkylthioureas) as novel platforms in nuclear medicine for 68Ga, 177Lu and 198Au.

BACKGROUND: Heterometallic gold metallacages are of great interest for the incorporation of several cations. Especially in nuclear medicine, those metallacages can serve as a platform for radionuclides relevant for imaging or therapy (e.g. 68Ga or 177Lu). Moreover, the radionuclide 198Au is an attractive beta emitter, for potential application in nuclear medicine. Here, we aim to synthesize a new set of gold metallacages and to study their ability to coordinate to 68Ga, 177Lu and 198Au. RESULTS: New heterometallic gold metallacages of composition [M{Au(Lmorph-κS)}3] (M = La3+, Tb3+, Lu3+ or Y3+) and [Ga{Au(Lmorph-κS)}2]NO3 have been synthesized from 2,6-dipicolinoylbis(N,N-morpholinylthiourea) (H2Lmorph) with [AuCl(THT)] and the target M3+ metal ions in yields ranging from 33 (Lu) to 62% (Tb). The characterization of the compounds bases on ESI-MS, 1H NMR, IR, EA and single-crystal X-ray diffraction techniques (all except the Ga derivative). Selected gold cages derived from H2Lmorph were compared to previously reported gold cages that were derived from 2,6-dipicolinoylbis(N,N-diethylthiourea) (H2Ldiethyl). The tested metallacages show similar IC50 values close to that of auranofin in four different cancer cell lines (MCF-7, PC-3, U383, U343), e.g. 4.5 ± 0.7 µM for [Ga{Au(Ldiethyl)}2]NO3 on PC-3. The radiolabeling experiments thereof show high radiochemical purities with 68Ga and 198Au and low radiochemical purity with 177Lu. CONCLUSIONS: The results indicate that these gold metallacages could serve as a novel platform for inclusion of different (radio)nuclides with potential theranostic applications in nuclear medicine.

Evaluation of the 177mLu-concentration in in-house produced 177Lu-radiopharmaceuticals and commercially available Lutathera®.

BACKGROUND: 177Lu-radiopharmaceuticals can contain the metastable impurity [177mLu]lutetium with a physical half-life of 160.4 days, in varying concentrations depending on the route of production of the radionuclidic precursor [177Lu]lutetium. Due to the long half-life of [177mLu]lutetium, difficulties with waste disposal or sterility testing could arise. Here, we analyzed several 177Lu-samples of different origins and suppliers regarding their 177mLu-concentration. RESULTS: All samples tested showed a 177mLu-concentration in the range that was stated on the certificate of analysis from the supplier which is in accordance with the European Pharmacopoeia. CONCLUSIONS: Although all 177mLu-concentrations were in accordance with the European Pharmacopoeia, we need to take into account the respective national legislation regarding radioactivity release limits. With regard to the German legislation, several probes for sterility testing in external laboratories could not be released for transport due to the concentration of [177mLu]lutetium. Moreover, waste water tanks should specifically be monitored for 177mLu-concentration, when e.g. Lutathera® is administered in the clinic.

Unified Bayesian network for uncertainty quantification of physiological parameters in dynamic contrast enhanced (DCE) MRI of the liver.

Objective. Physiological parameter estimation is affected by intrinsic ambiguity in the data such as noise and model inaccuracies. The aim of this work is to provide a deep learning framework for accurate parameter and uncertainty estimates for DCE-MRI in the liver.Approach. Concentration time curves are simulated to train a Bayesian neural network (BNN). Training of the BNN involves minimization of a loss function that jointly minimizes the aleatoric and epistemic uncertainties. Uncertainty estimation is evaluated for different noise levels and for different out of distribution (OD) cases, i.e. where the data during inference differs strongly to the data during training. The accuracy of parameter estimates are compared to a nonlinear least squares (NLLS) fitting in numerical simulations andin vivodata of a patient suffering from hepatic tumor lesions.Main results. BNN achieved lower root-mean-squared-errors (RMSE) than the NLLS for the simulated data. RMSE of BNN was on overage of all noise levels lower by 33% ± 1.9% forktrans, 22% ± 6% forveand 89% ± 5% forvpthan the NLLS. The aleatoric uncertainties of the parameters increased with increasing noise level, whereas the epistemic uncertainty increased when a BNN was evaluated with OD data. For thein vivodata, more robust parameter estimations were obtained by the BNN than the NLLS fit. In addition, the differences between estimated parameters for healthy and tumor regions-of-interest were significant (p< 0.0001).Significance. The proposed framework allowed for accurate parameter estimates for quantitative DCE-MRI. In addition, the BNN provided uncertainty estimates which highlighted cases of high noise and in which the training data did not match the data during inference. This is important for clinical application because it would indicate cases in which the trained model is inadequate and additional training with an adapted training data set is required.

ChatGPT: Can You Prepare My Patients for [18F]FDG PET/CT and Explain My Reports?

We evaluated whether the artificial intelligence chatbot ChatGPT can adequately answer patient questions related to [18F]FDG PET/CT in common clinical indications before and after scanning. Methods: Thirteen questions regarding [18F]FDG PET/CT were submitted to ChatGPT. ChatGPT was also asked to explain 6 PET/CT reports (lung cancer, Hodgkin lymphoma) and answer 6 follow-up questions (e.g., on tumor stage or recommended treatment). To be rated "useful" or "appropriate," a response had to be adequate by the standards of the nuclear medicine staff. Inconsistency was assessed by regenerating responses. Results: Responses were rated "appropriate" for 92% of 25 tasks and "useful" for 96%. Considerable inconsistencies were found between regenerated responses for 16% of tasks. Responses to 83% of sensitive questions (e.g., staging/treatment options) were rated "empathetic." Conclusion: ChatGPT might adequately substitute for advice given to patients by nuclear medicine staff in the investigated settings. Improving the consistency of ChatGPT would further increase reliability.

Predictive IDH Genotyping Based on the Evaluation of Spatial Metabolic Heterogeneity by Compartmental Uptake Characteristics in Preoperative Glioma Using 18F-FET PET.

Molecular markers are of increasing importance for classifying, treating, and determining the prognosis for central nervous system tumors. Isocitrate dehydrogenase (IDH) is a critical regulator of glucose and amino acid metabolism. Our objective was to investigate metabolic reprogramming of glioma using compartmental uptake (CU) characteristics in O-(2-18F-fluoroethyl)-l-tyrosine (FET) PET and to evaluate its diagnostic potential for IDH genotyping. Methods: Between 2017 and 2022, patients with confirmed glioma were preoperatively investigated using static 18F-FET PET. Metabolic tumor volume (MTV), MTV for 60%-100% uptake (MTV60), and T2-weighted and contrast-enhancing lesion volumes were automatically segmented using U-Net neural architecture and isocontouring. Volume intersections were determined using the Dice coefficient. Uptake characteristics were determined for metabolically defined compartments (central [80%-100%] and peripheral [60%-75%] areas of 18F-FET uptake). CU ratio was defined as the fraction between the peripheral and central compartments. Mean target-to-background ratio was calculated. Comparisons were performed using parametric and nonparametric tests. Receiver-operating-characteristic curves, regression, and correlation were used for statistical analysis. Results: In total, 52 participants (male, 27, female, 25; mean age ± SD, 51 ± 16 y) were evaluated. MTV60 was greater and distinct from contrast-enhancing lesion volume (P = 0.046). IDH-mutated tumors presented a greater volumetric CU ratio and SUV CU ratio than IDH wild-type tumors (P < 0.05). Volumetric CU ratio determined IDH genotype with excellent diagnostic performance (area under the curve [AUC], 0.88; P < 0.001) at more than 5.49 (sensitivity, 86%, specificity, 90%), because IDH-mutated tumors presented a greater peripheral metabolic compartment than IDH wild-type tumors (P = 0.045). MTV60 and MTV were not suitable for IDH classification (P > 0.05). SUV CU ratio (AUC, 0.72; P = 0.005) and target-to-background ratio (AUC, 0.68; P = 0.016) achieved modest diagnostic performance-inferior to the volumetric CU ratio. Furthermore, the classification of loss of heterozygosity of chromosomes 1p and 19q (AUC, 0.75; P = 0.019), MGMT promoter methylation (AUC, 0.70; P = 0.011), and ATRX loss (AUC, 0.73; P = 0.004) by amino acid PET was evaluated. Conclusion: We proposed parametric 18F-FET PET as a noninvasive metabolic biomarker for the evaluation of CU characteristics, which differentiated IDH genotype with excellent diagnostic performance, establishing a critical association between spatial metabolic heterogeneity, mitochondrial tricarboxylic acid cycle, and genomic features with critical implications for clinical management and the diagnostic workup of patients with central nervous system cancer.

Optimization of 177Lu-labelling of DOTA-TOC, PSMA-I&T and FAPI-46 for clinical application.

BACKGROUND: 177Lu-radiopharmaceuticals are routinely used for the treatment of various tumor entities. The productions of radiopharmaceuticals follow strict good-manufacturing practice guidelines and synthesis optimizations thereof have a strong impact on e.g. the quality of the product, radiation safety and costs. The purpose of this study is to optimize the precursor load of three radiopharmaceuticals. For that, different precursor loads were evaluated and compared to previously reported findings. RESULTS: All three radiopharmaceuticals were successfully synthesized in high radiochemical purities and yields on the ML Eazy. The precursor load was optimized for [177Lu]Lu-FAPI-46 from 27.0 to 9.7 µg/GBq, for [177Lu]Lu-DOTATOC from 11 to 10 µg/GBq and for [177Lu]Lu-PSMA-I&T from 16.3 to 11.6 µg/GBq. CONCLUSIONS: We successfully reduced the precursor load for all three radiopharmaceuticals while maintaining their quality.

[177Lu]Lu-PSMA Therapy as an Individual Treatment Approach for Patients with High-Grade Glioma: Dosimetry Results and Critical Statement.

The theranostic use of prostate-specific membrane antigen (PSMA) appears to be promising in patients with high-grade glioma. This study investigated [177Lu]Lu-PSMA therapy as an individual treatment approach with a focus on intratherapeutic dosimetry. Methods: Three patients were treated with a median of 6.03 GBq (interquartile range [IQR], 5.74-6.10) of [177Lu]Lu-PSMA. Intratherapeutic dosimetry was performed using a hybrid scenario with planar whole-body scintigraphy at 2, 24, and 48 h after treatment injection and SPECT/CT at 48 h after injection. Additive whole-body scintigraphy at 8 d after injection was performed on 1 patient. Results: The median doses were 0.56 Gy (IQR, 0.36-1.25 Gy) to tumor, 0.27 Gy (IQR, 0.16-0.57 Gy) to risk organs, 2.13 Gy (IQR, 1.55-2.89 Gy) to kidneys, and 0.76 Gy (IQR, 0.70-1.20 Gy) to salivary glands. Whole-body exposure was 0.11 Gy (IQR, 0.06-0.18 Gy). Conclusion: Because the intratherapeutic tumor dose is lower than that used in external radiation oncology, the effectiveness of treatment is questionable.

Same same but different: dopamine transporter SPECT on scanners with CZT vs. NaI detectors.

BACKGROUND: The aims of this study were to establish a normal database (NDB) for semiquantification of dopamine transporter (DAT) single-photon emission computed tomography (SPECT) with [123I]FP-CIT on a cadmium zinc telluride (CZT) camera, test the preexisting NaI-derived NDB for use in CZT scans, and compare the diagnostic findings in subjects imaged with a CZT scanner with either the preexisting NaI-based NDB or our newly defined CZT NDB. METHODS: The sample comprised 73 subjects with clinically uncertain parkinsonian syndrome (PS) who prospectively underwent [123I]FP-CIT SPECT on a CZT camera according to standard guidelines with identical acquisition and reconstruction protocols (DaTQUANT). Two experienced readers visually assessed the images and binarized the subjects into "non-neurodegenerative PS" and "neurodegenerative PS". Twenty-five subjects from the "non-neurodegenerative PS" subgroup were randomly selected to establish a CZT NDB. The remaining 48 subjects were defined as "test group". DaTQUANT was used to determine the specific binding ratio (SBR). For the test group, SBR values were transformed to z-scores for the putamen utilizing both the CZT NDB and the manufacturer-provided NaI-based NDB (GE NDB). A predefined fixed cut-off of -2 was used for dichotomization of z-scores to classify neurodegenerative and non-neurodegenerative PS. Performance of semiquantification using the two NDB to identify subjects with neurodegenerative PS was assessed in comparison with the visual rating. Furthermore, a randomized head-to-head comparison of both detector systems was performed semiquantitatively in a subset of 32 out of all 73 subjects. RESULTS: Compared to the visual rating as reference, semiquantification based on the dedicated CZT NDB led to fewer discordant ratings than the GE NDB in CZT scans (3 vs. 8 out of 48 subjects). This can be attributed to the putaminal z-scores being consistently higher with the GE NDB on a CZT camera (median absolute difference of 1.68), suggesting an optimal cut-off of -0.5 for the GE NDB instead of -2.0. Average binding ratios and z-scores were significantly lower in CZT compared to NaI data. CONCLUSIONS: Use of a dedicated, CZT-derived NDB is recommended in [123I]FP-CIT SPECT with a CZT camera since it improves agreement between semiquantification and visual assessment.

[Is there an unmet need to establish a young talent section "Young DGN" within the German Society of Nuclear Medicine (DGN)? - Results of a 2021/2022 web-based survey among German Nuclear Medicine professionals]. / Besteht der Bedarf zur Gründung einer Nachwuchsorganisation "Young DGN" innerhalb der Deutschen Gesellschaft für Nuklearmedizin (DGN)? Ergebnisse einer webbasierten Umfrage in der deutschen Nuklearmedizin 2021/2022.

AIM: In various medical societies, dedicated young talent sections provide an important basis for promoting young members. However, the German Society of Nuclear Medicine (DGN) had not yet implemented such a section. Therefore, the aim of this work was to assess the opinion of nuclear medicine professionals in Germany on establishing a young talent section within the DGN ("Young DGN"). METHODS: An initiative group of young DGN members developed a survey questionnaire comprising 18 questions. The questionnaire was initially sent as a PDF to the members of the DGN University Committee (Hochschulausschuss) by e-mail on 10/12/2021. As an online survey, the questionnaire was then emailed at four additional time points between 12/23/2021 and 3/18/2022 via the DGN eBrief and on 2/23/2022 to the members of the mailing list of the Berufsverband Deutscher Nuklearmediziner (BDN). RESULTS: The survey closed on 3/31/2022 with 111 responses (n=104 online surveys, n=7 PDFs). The median age of participants was 32.5 years (range, 20-80). 86% of participants indicated that they were interested in a Young DGN section, of which 67% were willing to participate. 79% indicated that nuclear medicine was an exciting field for them. 96% expressed interest in additional education offers and 60% in the establishment of a mentoring program. 75% believed that Young DGN would improve the visibility of the specialty. CONCLUSION: The survey results indicate strong support for the establishment of a young talent section within the DGN among nuclear medicine professionals in Germany. A large proportion of those who participated in the survey would envision active involvement. There was a particular consensus on the desire to expand the range of education and training activities.

[68Ga]Ga-PSMA PET/MRI, histological PSMA expression and preliminary experience with [177Lu]Lu-PSMA therapy in relapsing high-grade glioma.

Purpose: High-grade gliomas (HGG) are still associated with a dismal prognosis. Prostate specific membrane antigen (PSMA) is discussed as a theranostic target for PSMA-directed radioligand therapy ([177Lu]Lu-PSMA RLT). Here, we report on the correlation of [68Ga]Ga-PSMA uptake with histological PSMA expression and on our preliminary experience with [177Lu]Lu-PSMA RLT in relapsing HGG. Methods: Patients with relapsing HGG underwent [68Ga]Ga-PSMA PET/MRI to evaluate eligibility for an individualized treatment approach with [177Lu]Lu-PSMA. Standard uptake values (SUV) for tumor and liver and respective tumor-to-background ratios (compared to the liver) (TBR) on [68Ga]Ga-PSMA PET/MRI were assessed. Eligibility criteria for [177Lu]Lu-PSMA therapy were exhaustion of all standard treatment options available and TBRmax>1.0. In 11 samples, immunohistochemical PSMA expression was determined, quantified using the H-score and correlated with uptake on [68Ga]Ga-PSMA PET/MRI. Results: We included 20 patients with a median age of 53 years (IQR 42-57). The median SUV on [68Ga]Ga-PSMA PET/MRI was 4.5 (3.7-6.2) for SUVmax and 1.4 (1.1-1.7) for SUVmean. The respective TBR was maximum 0.6 (0.4-0.8) and mean 0.3 (0.2-0.4). High TBRmax correlated with increased endothelial PSMA expression [H-score of 65 (62.5-77.5)]. Three patients (15%) presented a TBRmax>1.0 and qualified for [177Lu]Lu-PSMA RLT. No treatment related toxicity was observed. Conclusion: Only a minority of patients with relapsing HGG qualified for [177Lu]Lu-PSMA RLT. Our data demonstrates that PSMA expression in the neo-vasculature corresponds to PSMA uptake on [68Ga]Ga-PSMA PET/MRI and might be used as a screening tool for patient selection. Future prospective studies need to focus the debate on TBRmax thresholds as inclusion criteria for PSMA RLT.

Monitoring orthodontic tooth movement in rats after piezocision by bone scintigraphy.

AIM: Piezocision, corticocision of mineralized tissue by ultrasound showed promising results in accelerating tooth movement induced by orthodontic appliances although the biologic effects of this procedure are not well-understood so far. The aim of this study was to investigate the impact of piezocision on bone remodeling in rats by bone SPECT imaging. MATERIAL AND METHODS: Ten male Wistar rats underwent surgical placement of orthodontic appliances on each side of the maxilla followed by piezocision on one side only. Each rat underwent 99mTc-MDP bone SPECT/CT imaging before surgery (T0), and 2 (T1) and 4 weeks (T2) after surgery. Bone uptake is expressed as median [IQR] min-max in percentage of the injected activity per ml computed from the 10 voxels with the highest uptake (%IAmax10/ml). RESULTS: Pooled data regardless of the piezocision showed a significant increase in bone uptake from T0 (3.2 [2.8-3.9] 2.6-4.9) to T1 (4.4 [3.8-4.6] 3.4-4.8; p = 0.001). Thereafter, the uptake decreased to T2 (3.8 [3.1-4.4] 2.8-4.8; p = 0.116). No significant differences in bone uptake were found between the maxilla sides without and with piezocision: T1: without (4.3 [3.8-4.5] 3.4-4.8) vs. with (4.5 [3.7-4.6] 3.5-4.7; p=0.285), T2: without (4.0 [3.1-4.5] 2.8-4.8) vs. with (3.7 [3.0-4.4] 2.8-4.8; p=0.062). CONCLUSION: 99mTc-MDP bone SPECT imaging in rats was able to reproduce changes in bone uptake in the maxilla after placement of orthodontic appliances inducing measurable tooth movement. An additional effect of piezocision on bone remodeling in terms of bone uptake was not detectable which is probably due to the pronounced and significant effects induced by the orthodontic appliances per se, which may mask the potential effects of additional piezocision.

Comparison of Choi, RECIST and Somatostatin Receptor PET/CT Based Criteria for the Evaluation of Response and Response Prediction to PRRT.

Aim: The most suitable method for assessment of response to peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET) is still under debate. In this study we aimed to compare size (RECIST 1.1), density (Choi), Standardized Uptake Value (SUV) and a newly defined ZP combined parameter derived from Somatostatin Receptor (SSR) PET/CT for prediction of both response to PRRT and overall survival (OS). Material and Methods: Thirty-four NET patients with progressive disease (F:M 23:11; mean age 61.2 y; SD ± 12) treated with PRRT using either Lu-177 DOTATOC or Lu-177 DOTATATE and imaged with Ga-68 SSR PET/CT approximately 10-12 weeks prior to and after each treatment cycle were retrospectively analyzed. Median duration of follow-up after the first cycle was 63.9 months (range 6.2-86.2). A total of 77 lesions (2-8 per patient) were analyzed. Response assessment was performed according to RECIST 1.1, Choi and modified EORTC (MORE) criteria. In addition, a new parameter named ZP, the product of Hounsfield unit (HU) and SUVmean (Standard Uptake Value) of a tumor lesion, was tested. Further, SUV values (max and mean) of the tumor were normalized to SUV of normal liver parenchyma. Tumor response was defined as CR, PR, or SD. Gold standard for comparison of baseline parameters for prediction of response of individual target lesions to PRRT was change in size of lesions according to RECIST 1.1. For prediction of overall survival, the response after the first and second PRRT were tested. Results: Based on RECIST 1.1, Choi, MORE, and ZP, 85.3%, 64.7%, 61.8%, and 70.6% achieved a response whereas 14.7%, 35.3%, 38.2%, and 29.4% demonstrated PD (progressive disease), respectively. Baseline ZP and ZPnormalized were found to be the only parameters predictive of lesion progression after three PRRT cycles (AUC ZP 0.753; 95% CI 0.6-0.9, p 0.037; AUC ZPnormalized 0.766; 95% CI 0.6-0.9; p 0.029). Based on a cut-off-value of 1201, ZP achieved a sensitivity of 86% and a specificity of 67%, while ZPnormalized reached a sensitivity of 86% and a specificity of 76% at a cut-off-value of 198. Median OS in the total cohort was not reached. In univariate analysis amongst all parameters, only patients having progressive disease according to MORE after the second cycle of PRRT were found to have significantly shorter overall survival (median OS in objective responders not reached, in PD 29.2 months; p 0.015). Patients progressive after two cycles of PRRT according to ZP had shorter OS compared to those responding (median OS for responders not reached, for PD 47.2 months, p 0.066). Conclusions: In this explorative study, we showed that Choi, RECIST 1.1, and SUVmax-based response evaluation varied significantly from each other. Only patients showing progressive disease after two PRRT cycles according to MORE criteria had a worse prognosis while baseline ZP and ZPnormalized performed best in predicting lesion progression after three cycles of PRRT.

[Radioiodine testing in clinical routine: Status in Germany 2021]. / Statuserfassung des Radiojodtests im klinischen Alltag in Deutschland 2021.

INTRODUCTION AND AIM: According to the German guideline on Radiation Protection in Medicine, the activity to be applied for radioiodine therapy of benign thyroid diseases is determined for each patient by means of the radioiodine test (RJT). The aim of this study is to record the different parameters of the RJT. MATERIAL AND METHODS: A web-based questionnaire was sent to all nuclear medicine departments in Germany via the DGN office. Parameters regarding tracer and activity, type of probe measurement, number and timing of measurements, use of fixed effective half-lives (eHWZ), calculation model and organ doses were requested. An assessment of continuous measurement of the thyroid iodine uptake over seven days by a wearable probe system was also requested. RESULTS: 38 of 94 facilities responded to the questionnaire. Major differences in RJT implementation were found concerning the parameters number and timing of measurements, probe-patient distance, use of fixed disease-specific eHWZ, and intended organ dose. Despite the DGN Guideline and DIN 6861-1, 74% of the facilities still use the simplified Marinelli formula from the DGN Recommendation of 1998. Only 8% have switched to the two-compartment model. 84% of the institutions expect that a wearable probe system could improve the calculation of the radioiodine activity necessary for treatment, but only 57% expect an improvement in the therapeutic outcome. CONCLUSIONS: The methodology of RJT in Germany is heterogeneous and still based on the "Marinelli method" in most institutions despite new guidelines and recommendations. A continuous measurement of the iodine kinetics using a wearable probe system could result in further improving the radioiodine test in addition to the newer calculation algorithms.

Dynamic 18F-FET PET/CT to differentiate recurrent primary brain tumor and brain metastases from radiation necrosis after single-session robotic radiosurgery.

OBJECTIVE: Cyberknife robotic radiosurgery (RRS) provides single-session high-dose radiotherapy of brain tumors with a steep dose gradient and precise real-time image-guided motion correction. Although RRS appears to cause more radiation necrosis (RN), the radiometabolic changes after RRS have not been fully clarified. 18F-FET-PET/CT is used to differentiate recurrent tumor (RT) from RN after radiosurgery when MRI findings are indecisive. We explored the usefulness of dynamic parameters derived from 18F-FET PET in differentiating RT from RN after Cyberknife treatment in a single-center study population. METHODS: We retrospectively identified brain tumor patients with static and dynamic 18F-FET-PET/CT for suspected RN after Cyberknife. Static (tumor-to-background ratio) and dynamic PET parameters (time-activity curve, time-to-peak) were quantified. Analyses were performed for all lesions taken together (TOTAL) and for brain metastases only (METS). Diagnostic accuracy of PET parameters (using mean tumor-to-background ratio >1.95 and time-to-peak of 20 min for RT as cut-offs) and their respective improvement of diagnostic probability were analyzed. RESULTS: Fourteen patients with 28 brain tumors were included in quantitative analysis. Time-activity curves alone provided the highest sensitivities (TOTAL: 95%, METS: 100%) at the cost of specificity (TOTAL: 50%, METS: 57%). Combined mean tumor-to-background ratio and time-activity curve had the highest specificities (TOTAL: 63%, METS: 71%) and led to the highest increase in diagnosis probability of up to 16% p. - versus 5% p. when only static parameters were used. CONCLUSIONS: This preliminary study shows that combined dynamic and static 18F-FET PET/CT parameters can be used in differentiating RT from RN after RRS.

Simultaneous [18F]fluoride and gadobutrol enhanced coronary positron emission tomography/magnetic resonance imaging for in vivo plaque characterization.

AIMS: 18F-sodium fluoride ([18F]fluoride) and gadobutrol are promising probes for positron emission tomography (PET) and magnetic resonance imaging (MRI) characterizing coronary artery disease (CAD) activity. Unlike [18F]fluoride-PET/computed tomography (CT), the potential of PET/MR using [18F]fluoride and gadobutrol simultaneously, has so far not been evaluated. This study assessed feasibility and diagnostic potential of [18F]fluoride and gadobutrol enhanced dual-probe PET/MR in patients with CAD. METHODS AND RESULTS: Twenty-one patients (age, 66.7 ± 6.7 years) with CAD scheduled for invasive coronary angiography (XCA) underwent simultaneous [18F]fluoride (mean activity/effective dose: 157.2 ± 29.7 MBq/3.77 ± 0.72 mSv) and gadobutrol enhanced PET/MR on an integrated PET/MRI (3 T) scanner. Optical coherence tomography (OCT) was used as reference. Target-to-background ratio (TBR, [18F]fluoride-PET) and contrast-to-noise ratio (CNR) values (MRI, gadobutrol) were calculated for each coronary segment. Previously suggested PET/CT-TBR thresholds for adverse coronary events were evaluated. High-risk plaques, i.e. calcified and non-calcified thin-cap fibroatheromas (TCFAs) were predominantly located in segments with a TBR >1.28 (P = 0.012). Plaques containing a lipid core on OCT, were more frequently detected in segments with a TBR >1.25 (P < 0.001). TBR values significantly correlated with maximum calcification thickness (P = 0.009), while fibrous cap thickness was significantly less in segments with a TBR >1.28 (P = 0.044). Above a TBR threshold of >1.28, CNR values significantly correlated with the presence of calcified TCFAs (P = 0.032). CONCLUSION: Simultaneous [18F]fluoride and gadobutrol dual-probe PET/MRI is feasible in clinical practice and may facilitate the identification of high-risk patients. The combination of coronary MR-derived CNR values post gadobutrol and [18F]fluoride based TBR values may improve identification of high-risk plaque features.

68Ga-NODAGA-Exendin-4 PET/CT Improves the Detection of Focal Congenital Hyperinsulinism.

Surgery with curative intent can be offered to congenital hyperinsulinism (CHI) patients, provided that the lesion is focal. Radiolabeled exendin-4 specifically binds the glucagonlike peptide 1 receptor on pancreatic ß-cells. In this study, we compared the performance of 18F-DOPA PET/CT, the current standard imaging method for CHI, and PET/CT with the new tracer 68Ga-NODAGA-exendin-4 in the preoperative detection of focal CHI. Methods: Nineteen CHI patients underwent both 18F-DOPA PET/CT and 68Ga-NODAGA-exendin-4 PET/CT before surgery. The images were evaluated in 3 settings: a standard clinical reading, a masked expert reading, and a joint reading. The target (lesion)-to-nontarget (normal pancreas) ratio was determined using SUVmax Image quality was rated by pediatric surgeons in a questionnaire. Results: Fourteen of 19 patients having focal lesions underwent surgery. On the basis of clinical readings, the sensitivity of 68Ga-NODAGA-exendin-4 PET/CT (100%; 95% CI, 77%-100%) was higher than that of 18F-DOPA PET/CT (71%; 95% CI, 42%-92%). Interobserver agreement between readings was higher for 68Ga-NODAGA-exendin-4 than for 18F-DOPA PET/CT (Fleiss κ = 0.91 vs. 0.56). 68Ga-NODAGA-exendin-4 PET/CT provided significantly (P = 0.021) higher target-to-nontarget ratios (2.02 ± 0.65) than did 18F-DOPA PET/CT (1.40 ± 0.40). On a 5-point scale, pediatric surgeons rated 68Ga-NODAGA-exendin-4 PET/CT as superior to 18F-DOPA PET/CT. Conclusion: For the detection of focal CHI, 68Ga-NODAGA-exendin-4 PET/CT has higher clinical sensitivity and better interobserver correlation than 18F-DOPA PET/CT. Better contrast and image quality make 68Ga-NODAGA-exendin-4 PET/CT superior to 18F-DOPA PET/CT in surgeons' intraoperative quest for lesion localization.