Guiding principles on the education and practice of theranostics.

PURPOSE: The recent development and approval of new diagnostic imaging and therapy approaches in the field of theranostics have revolutionised nuclear medicine practice. To ensure the provision of these new imaging and therapy approaches in a safe and high-quality manner, training of nuclear medicine physicians and qualified specialists is paramount. This is required for trainees who are learning theranostics practice, and for ensuring minimum standards for knowledge and competency in existing practising specialists. METHODS: To address the need for a training curriculum in theranostics that would be utilised at a global level, a Consultancy Meeting was held at the IAEA in May 2023, with participation by experts in radiopharmaceutical therapy and theranostics including representatives of major international organisations relevant to theranostics practice. RESULTS: Through extensive discussions and review of existing curriculum and guidelines, a harmonised training program for theranostics was developed, which aims to ensure safe and high quality theranostics practice in all countries. CONCLUSION: The guiding principles for theranostics training outlined in this paper have immediate relevance for the safe and effective practice of theranostics.

Abnormal liver findings as the first manifestation in a patient with brucellosis : Case report.

In January 2019, a 30-year-old woman admitted to our inpatient department presented with undulating fever, pain in several joints, and significantly elevated liver enzymes and lactate dehydrogenase. After extended examination, infection with Brucella melitensis with liver, musculoskeletal, and pulmonary involvement was diagnosed and treated. Diagnosis was based on clinical examination, laboratory findings including seroconversion as a proof of immune response, magnetic resonance imaging, three-phase bone scintigraphy, and F­18 FDG-PET (F-18 Flourdeoxyglucose positron emission tomography) illustrating the bone involvement and its normalization upon treatment. After treatment the patient showed a remarkable improvement of clinical symptoms within a short period. The patient remained symptom free and polymerase chain reaction (PCR) testing for brucellosis was negative, even at the follow-up examination 12 months after the end of the antibiotic therapy. The family members were also examined due to the similar travel history, and by this, brucellosis was also diagnosed in her husband but not in her children.

Peptide and pseudo-peptide.

In recent years, the introduction of theranostic twins for specific diagnosis and treatment in patients with neuroendocrine tumors became a nuclear medicine success story. 64Cu/18F labeled prostate specific membrane antigen (PSMA) for molecular imaging with PET-CT and peptide radioligand therapy with 177Lu labeled PSMA inhibitors will favorably become the next theranostic twins in nuclear medicine history. 68Ga/ 64Cu/18F PSMA PET/CT detects metastatic prostate cancer with high diagnostic sensitivity and specificity. In addition, it can be used to select patients for radioligand therapy and evaluate therapy response. 64Cu-labeled radiopharmaceuticals such as 64Cu-PSMA, and 64Cu-somatostatin analogs are promising imaging tools in the assessment of primary disease and also in the detection of disease recurrence and to evaluate therapy response. The long half-life of 64Cu allows the distribution of the tracer to PET centers as a satellite concept, who otherwise has no access to 68Ga generators.

Radiofrequency ablation of thyroid nodules: "Good Clinical Practice Recommendations" for Austria : An interdisciplinary statement from the following professional associations: Austrian Thyroid Association (ÖSDG), Austrian Society for Nuclear Medicine and Molecular Imaging (OGNMB), Austrian Society for Endocrinology and Metabolism (ÖGES), Surgical Endocrinology Working Group (ACE) of the Austrian Surgical Society (OEGCH).

The present "Good Clinical Practice Recommendations" relate to radiofrequency ablation (RFA) training, execution, and quality control, as well as to pre- and postinterventional standards of care. They are aimed at all physicians who intend to learn to perform, or who are already conducting RFA interventions as well as at thyroid specialists providing pre- and postoperative care to RFA patients in Austria. Adoption of these recommendations is strongly encouraged by the afore-listed professional associations.All RFA interventionists who adhere to these standards shall be listed on a homepage linked to these professional associations entitled "RFA centers in compliance with the GCP recommendations of the ÖSDG/OGNMB/ÖGES/OEGCH-ACE." This will ensure harmonization of RFA training and quality control in the performance of the treatment in Austria.

[The role of molecular imaging (PET-CT) in the diagnostic and treatment pf prostate cancer]. / Die Rolle der molekularen Bildgebung (PET-CT) in der Diagnostik und Therapie des Prostatakarzinoms.

Prostate cancer is the most frequent cancer type in men in industrialized countries. In case of biochemical recurrent disease of prostate cancer is molecular imaging with PET-CT or PET-MRI a very promising modality for the detection of local recurrence, lymph node involvement or distant metastasis. Of the so far implemented radiopharmaceuticals the radioactive labeled PSMA ligands (i. e. Ga-68 PSMA) have prevailed. There are also in the meanwhile treatment approaches with PSMA ligands (i. e. Lu-177 PSMA) in case of metastatic disease.

Image fusion between 18F-FDG PET and MRI in cardiac sarcoidosis: A case series.

BACKGROUND: Sarcoidosis is a systemic disorder of unknown etiology. It is distinguished by the presence of noncaseating epithelioid granulomas. This study demonstrates the use of image fusion between (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) and magnetic resonance imaging (MRI) to diagnose patients with cardiac sarcoidosis (CS). METHODS: Seven patients diagnosed with sarcoidosis were retrospectively included. All patients underwent 18F-FDG PET/CT and cardiac MRI. RESULTS: On the MRI scan, late gadolinium enhancement (LGE) was observed in five patients. T2-weighted images revealed areas with an increased signal consistent with myocardial edema in two patients and with hypointensity suggesting fibrosis in one patient. Increased 18F-FDG uptake was seen in the myocardial wall in three patients, indicating active inflammation. CONCLUSION: 18F-FDG PET and MRI image fusion allows clinicians to obtain complete morphofunctional cartography in patients with sarcoidosis. Our data show that 18F-FDG PET/MRI image fusion imaging can be useful in the diagnosis of CS.

Acoustic Structure Quantification Analysis of the Thyroid in Patients with Diffuse Autoimmune Thyroid Disease.

The aim of this study was to assess whether acoustic structure quantification (ASQ) can differentiate normal from pathological thyroid parenchyma in patients with diffuse autoimmune thyroid disease (AITD). We evaluated 83 subjects (72 [87%] women and 11 [13%] men) aged 19 to 94 years with a mean age of 53 years. We performed a prospective study (from March 2011 to November 2014) that included 43 (52%) patients with chronic autoimmune thyroiditis (CAT), 22 (26%) patients with Graves' disease (GD), and 18 (22%) healthy volunteers. The ASQ values were significantly lower in normal subjects than in subjects with CAT and GD (p < 0.001). In contrast, the differences between the GD and the CAT patients (p = 0.23) were not statistically significant. The optimal cutoff ASQ value for which the sum of sensitivity and specificity was the highest for the prediction of diffuse thyroid pathology was 103 (95% confidence interval = [0.79, 0.95]). At this cutoff value, the sensitivity was 83% and the specificity was 89%. Our findings suggest that ASQ is a useful method for the assessment of the thyroid in patients with AITD.

Oncocytic adenomas of thyroid-mimicking benign or metastatic disease on 18F-FDG-PET scan.

BACKGROUND: The literature is sparse concerning 18F-fluorodeoxyglucose (18F-FDG) accumulation in the Hürthle cell neoplasm (HCN) of the thyroid. Given the difficulty of accurately diagnosing HCN, even with ultrasound (US) and fine needle aspiration biopsy (FNAB), the ability to accurately characterize these lesions by 18F-FDG positron emission tomography (PET) would be of value. PURPOSE: To describe six cases of oncocytic proliferation in the thyroid gland that mimics the presence of metastatic disease and was detected incidentally by an 18F-FDG PET scan. MATERIAL AND METHODS: We conducted whole-body 18F-FDG PET examinations for cancer staging in 1862 oncological patients from 2012 to 2013. Among them, six subjects (4 women, 2 men; age range, 45-85 years) with focal-enhanced 18F-FDG accumulation in the thyroid gland were selected from the study population. This study group was further investigated using 99 m-Tc-pertechnetate scintigraphy, US, and FNAB. Two experienced nuclear physicians reviewed the images. Gray-scale US and color Doppler (CD) sonographic examinations of the thyroid were undertaken for all subjects using a sonographic device Logiq 5 Expert (GE Medical Systems, Osaka, Japan) equipped with a 7-12 MHz linear array transducer. RESULTS: In all six cases, abnormal 18F-FDG uptake was found locally in the thyroid. The average SUVmax of the HCN was 5.8 (range, 2.6-16). In all six cases, 99 m-Tc-pertechnetate scintigraphy showed a cold spot. Compared with normal parenchymal vascularity, five of the six masses were shown to be hypervascular by CD ultrasonography. CONCLUSION: On PET scans, oncocytic proliferations of the thyroid may mimic metastases of other malignancies. The focal-enhanced uptake of 18F-FDG PET may be associated with a focal increase in the metabolic activity of the thyroid parenchyma due to the presence of oncocytes. Our study emphasizes the importance of obtaining cytological evidence before making a diagnosis of metastatic disease.

Single-dose GSTP1 prevents infarction-induced heart failure.

BACKGROUND: Heart failure (HF) is a common and often fatal complication of myocardial infarction (MI). Glutathione S-transferase P1-1 (GSTP1) has antiapoptotic and antiinflammatory effects and is a specific serum marker in HF patients. However, its role in HF treatment is unknown. METHODS AND RESULTS: GSTP1 effect was examined in a rat MI-induced HF model. Magnetic resonance imaging was used to examine cardiac function. GSTP1 and tumor necrosis factor α receptor-associated factor 2 (TRAF2) mRNA and protein expression were elevated in failing myocardium, although GSTP-1 binding activity to TRAF2 was not changed versus control. HF was associated with higher active JNK1 and p38 protein expression but reduced GSTP-1 binding activity to JNK1 and p38. Recombinant GSTP1 inhibited JNK1 and p38 and enhanced its own binding activity to TRAF2 and JNK1 in vitro. In the HF model, single-dose GSTP1 treatment reduced infarct area, apoptosis, and the expression of JNK1, p38, nuclear factor κB, and proinflammatory cytokines and improved thinning ratio, cardiac index and output, stroke volume, ejection fraction, regional wall motion, and survival compared with control. CONCLUSIONS: GSTP1 application early after MI results in long-term beneficial structural and functional effects that prevent progression to HF. GSTP1 could be a novel adjunct myocardial salvage approach in patients after MI.

Global Research Output of Lutetium-177 PSMA in Prostate Cancer: Bibliometric and Altmetric Analyses.

AIM: The integration of innovative radio-pharmaceutical agents targeting prostate-specific membrane antigen (PSMA) within nuclear medicine has transformed prostate cancer detection and management. This study aims to investigate the present landscape of [177Lu]Lu-PSMA in prostate cancer, elucidating trends, global contributions, scholarly outlets, institutions, and thematic concentrations with an aim to inform forthcoming research endeavors. METHODS: We systematically probed the Scopus repository for relevant [177Lu]Lu-PSMA literature. An assessment of bibliometric and altmetric data was carried out. Finally, we assessed the correlation between the altmetric attention scores and the number of citations for the retrieved data. RESULTS: Spanning January 2015 to July 2023, the study encompassed 466 articles concerning [177Lu]Lu-PSMA therapy for prostate cancer. Predominant citation accolades gravitated towards metastatic castration-resistant prostate cancer investigations and assessments of [177Lu]Lu-PSMA therapy's safety and efficacy. Further research encompassed adverse effects linked to [177Lu]Lu-PSMA intervention, including xerostomia, thrombocytopenia, anemia, and fatigue. Germany emerged as the primary academic contributor, with The Journal of Nuclear Medicine dominating publications (n = 55). A moderate significant correlation was detected between the number of citations and altmetric attention scores . CONCLUSION: The findings highlight the growing interest and advancements in the utilization of [177Lu]Lu-PSMA therapy in prostate cancer and offer a comprehensive global perspective on future research directions.

[Rare differential diagnosis in bilateral gonalgia]. / Seltene Differenzialdiagnose bei bilateraler Gonalgie.

We report on a 47-year-old patient suffering from bilateral gonalgia, weight loss and night sweats without fever of several months' duration. Diagnostic work-up for infectious and autoimmune diseases showed no abnormal results. A CT scan showed extensive foci of sclerosis throughout the axial skeleton. In the trephine biopsy, foamy cell infiltrates were found with expression of histiocytic markers without expression of Langerhans cell markers. Molecular analysis revealed a low allelic BRAF V600E and BCOR mutation. The diagnosis of Erdheim-Chester disease (ECD) was made. The histologic findings and molecular findings, the clinical and radiologic presentation before and 6 months after therapy as well as possible differential diagnoses of this very rare disease are discussed.

Evaluation of MRI-based radiomic features in heart morphologic variations as a consequence of autoimmune thyroid disorders.

Radiomics (RC) was initially developed using computed tomography (CT) for oncological imaging. However, it can be applied to various scientific and clinical radiology fields regardless of the modalities involved. The purpose of this survey was to evaluate alterations in magnetic resonance imaging of the heart (CMR) in patients suffering from autoimmune thyroid disorders (AITD) by applying RC tools and mapping features. A total of 50 individuals were evaluated in this study. We searched for CMR examinations performed in our department between January 2019 and 2021 in patients with AITD. Thirty patients with AITD (21 men and 9 women, aged 51 to 78 years; mean age, 60 years) were enrolled in our survey. We enrolled a control group (CG) of 20 individuals (14 men and 6 women aged 53-87 years; mean age, 68 years) without AITD or cardiac disorders. Global native T1 and T2 mapping revealed no significant differences between groups. However, we identified significantly higher values of several texture parameters, including the gray-level co-occurrence matrix (GLCM) entropy, gray-level run-length matrix (GLRLM; short-run high gray-level emphasis (SRHGE), GLCM (Energy), gray-level size zone matrix length matrix (GLZLM; LZLGE), GLZLM (SZLGE), DISCRETIZED (HISTO-Energy) GLCM (Dissimilarity), and GLCM (Contrast), in patients with AITD in comparison to the CG (P < .01). Our results indicate that several RC properties extracted from CMR images can be used to discriminate between the AITD and CG groups.

Diagnostic Value of Radiolabelled Somatostatin Analogues for Neuroendocrine Tumour Diagnosis: The Benefits and Drawbacks of [64Cu]Cu-DOTA-TOC.

Neuroendocrine tumours (NETs) arise from secondary epithelial cell lines in the gastrointestinal or respiratory system organs. The rate of development of these tumours varies from an indolent to an aggressive course, typically being initially asymptomatic. The identification of these tumours is difficult, particularly because the primary tumour is often small and undetectable by conventional anatomical imaging. Consequently, diagnosis of NETs is complicated and has been a significant challenge until recently. In the last 30 years, the advent of novel nuclear medicine diagnostic procedures has led to a substantial increase in NET detection. Great varieties of exclusive single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals for detecting NETs are being applied successfully in clinical settings, including [111In]In-pentetreotide, [99mTc]Tc-HYNIC-TOC/TATE, [68Ga]Ga-DOTA-TATE, and [64Cu]Cu-DOTA-TOC/TATE. Among these tracers for functional imaging, PET radiopharmaceuticals are clearly and substantially superior to planar or SPECT imaging radiopharmaceuticals. The main advantages include higher resolution, better sensitivity and increased lesion-to-background uptake. An advantage of diagnosis with a radiopharmaceutical is the capacity of theranostics to provide concomitant diagnosis and treatment with particulate radionuclides, such as beta and alpha emitters including Lutetium-177 (177Lu) and Actinium-225 (225Ac). Due to these unique challenges involved with diagnosing NETs, various PET tracers have been developed. This review compares the clinical characteristics of radiolabelled somatostatin analogues for NET diagnosis, focusing on the most recently FDA-approved [64Cu]Cu-DOTA-TATE as a state-of-the art NET-PET/CT radiopharmaceutical.

Diagnostic Reference Levels for nuclear medicine imaging in Austria: A nationwide survey of used dose levels for adult patients.

PURPOSE: To assess dose levels in routine nuclear medicine (NUC) procedures in Austria as a prior to a legislative update of the National Diagnostic Reference Levels (NDRL). METHOD: As part of a nationwide survey of common NUC-examinations between June 2019 and November 2019, data sets were collected from 33 Austrian hospitals with NUC equipment. All hospitals were asked to report the NUC imaging devices in use (model, type, year of manufacture, detector material, collimators), the standard protocol parameters for selected examinations (standard activity, collimator, average acquisition time, reconstruction type, use of time-of-flight) and to report data from 10 representative examinations (e.g. injected activity, weight), incl. the most common NUC-examinations for planar imaging/SPECT and PET. Median/mean values for injected activity were calculated and compared to current Austrian and international NDRL. A Pearson correlation coefficient was computed comparing different variables. RESULTS: In total, all 33 hospitals (100% response rate) reported data for this study for 60 SPECT devices, 21 PET/CT devices and 23 scintigraphy devices. Fixed activity values for scintigraphy/SPECT and PET were employed by about 90% and 56% of the hospitals, respectively. The most widely performed examinations for scintigraphy/SPECT are bone imaging, thyroid imaging, renal imaging (with MAG3/EC) and lung perfusion imaging (in 88% of the hospitals) and F-18 FDG-PET studies for oncology indications (in 100% of the hospitals). Significant correlations were found for patient weight and injected activity (scintigraphy/SPECT), use of iterative reconstruction and injected activity (PET) as well as size of field-of-view and injected activity (PET). CONCLUSIONS: The reported injected activity levels were comparable to those in other countries. However, for procedures for which NDRL exist, deviations in injected activities of >20% compared to the NDRL were found. These deviations are assumed to result mainly from advances in technology but also from deviations between NDRL and prescribed activities as given in the information leaflets of the radiopharmaceuticals.

Additional lesions detected in therapeutic scans with 177Lu-DOTATATE reflect higher affinity of 177Lu-DOTATATE for somatostatin receptors.

OBJECTIVE: Peptide receptor-targeted radionuclide therapy (PRRT) of somatostatin receptor (SR)-expressing neuroendocrine tumors (NETs) has become an established therapeutic option in patients with advanced NETs. The aim of this study was to compare the lesion detection rate of (99m)Tc-EDDA/HYNIC-TOC, a newly developed tracer for NET imaging, with (177)Lu-DOTATATE used for PRRT. METHODS: 8 patients (4 women, 4 men, age range 46-76 years) with histologically proven NETs, who showed high SR loads by (99m)Tc-EDDA/HYNIC-TOC scintigraphy, were treated with (177)Lu-DOTATATE. After treatment, all patients were subjected to whole-body scintigraphy with additional low-dose single-photon emission computed tomography (SPECT-CT) of the chest and abdomen. RESULTS: All patients demonstrated (177)Lu-DOTATATE accumulation in all lesions previously detected by (99m)Tc- EDDA/HYNIC-TOC scintigraphy. Three patients showed additional lesions in the liver and lungs. CONCLUSIONS: SPECT-CT after (177)Lu-DOTATATE therapy may be helpful in detecting additional lesions not seen using (99m)Tc-EDDA/HYNIC-TOC. This could reflect the broader affinity of (177)Lu-DOTATATE for SRs compared with (99m)Tc-EDDA/HYNIC-TOC.

Soft tissue metastasis of the penis detected by copper-64 labeled prostate-specific membrane antigen positron emission tomography (64Cu-PSMA PET/CT) in a patient with prostate cancer.

Prostate cancer is considered to be the most common solid cancer affecting men worldwide and leading to a significant morbidity and mortality. Metastases are usually seen in bone or lymph nodes. For recurrent disease, PET imaging with 68Ga-PSMA-11 (also known as HBED-CC, Glu-urea-Lys(Ahx)-HBED-CC, and PSMA-HBED-CC) is widely used. However, preparation of 68Ga-PSMA ligand requires the presence of radiochemistry facilities and can therefore not be utilized in centers lacking such facilities. Recently, copper labeled prostate-specific membrane antigen positron emission tomography (64Cu-PSMA PET/CT) demonstrated promising results in patients with recurrent disease and in the primary staging of selected patients with progressive local disease. In the present case, a rare manifestation site of a metastatic lesion in a patient with advanced prostate cancer is detected by 64Cu-PSMA PET/CT.

Single-Center Comparison of [64Cu]-DOTAGA-PSMA and [18F]-PSMA PET-CT for Imaging Prostate Cancer.

INTRODUCTION: the diagnostic performance of [64Cu]-DOTAGA-PSMA PET-CT imaging was compared retrospectively to [18F]-PSMA PET-CT in prostate cancer patients with recurrent disease and in the primary staging of selected patients with advanced local and possible metastatic disease. METHODS: We retrospectively selected a total of 100 patients, who were consecutively examined in our department, with biochemical recurrence after radical prostatectomy or who had progressive local and possible metastatic disease in the last 3 months prior to this investigation. All patients were examined with a dedicated PET-CT scanner (Biograph; Siemens Healthineers). A total of 250 MBq (3.5 MBq per kg bodyweight, range 230-290 MBq) of [64Cu]-DOTAGA-PSMA or [18-F]-PSMA was applied intravenously. PET images were performed 1 h post-injection (skull base to mid-thigh). The maximum standardized uptake values (SUVmax) of PSMA-positive lesions and the mean standardized uptake value (SUVmean) of the right liver lobe were measured. RESULTS: All but 9/50 of the patients (18%; PSA range: 0.01-0.7 µg/L) studied with [64Cu]-DOTAGA-PSMA and 6/50 of the ones (12%; PSA range: 0.01-4.2) studied with [18F]-PSMA had at least one positive PSMA lesion shown by PET-CT. The total number of lesions was higher with [64Cu]-DOTAGA-PSMA (209 vs. 191); however, the median number of lesions was one for [64Cu]-DOTAGA-PSMA and two for [18F]-PSMA. Interestingly, the median SUVmean of the right liver lobe was slightly higher for [18F]-PSMA (11.8 vs. 8.9). CONCLUSIONS: [64Cu]-DOTAGA-PSMA and [18F]-PSMA have comparable detection rates for the assessment of residual disease in patients with recurrent or primary progressive prostate cancer. The uptake in the liver is moderately different, and therefore at least the SUVs of the lesions in both studies would not be comparable.