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.

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.

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.

[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.

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.

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.

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.

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.

Stroke-Like Lesion in an m.3243A>G Carrier Presenting as Hyperperfusion and Hypometabolism.

Carriers of the m.3243A>G variant typically manifest with stroke-like episodes (SLEs), of which the morphological correlate on imaging is the stroke-like lesion (SLL). The pathophysiology of SLLs is poorly understood but acute and chronic stages are delineated. Here we present the case of an m.3243A>G carrier who presented with hypometabolism during his second SLL. The patient was a 56-year-old male who was diagnosed with MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) at the age of 50 upon a third SLE, muscle biopsy, and the detection of the m.3243A>G variant in the muscle. A fluorodeoxyglucose-positron emission tomography (FDG-PET) during the second SLE revealed hypometabolism in the occipital lobes bilaterally. The patient was misdiagnosed for years and was repeatedly exposed to mitochondrion-toxic drugs (metformin, steroids, valproic acid, oxcarbazepine, zolpidem). The previous data and the present findings indicate that the hypometabolism on FDG-PET together with reduced oxygen-extraction fraction (OEF) on OEF-MRI and hyperperfusion on perfusion-weighted imaging (PWI) characterise best the acute stage of an SLL. In conclusion, an acute SLE in m.3243A>G carriers typically manifests with a mismatch between hyperperfusion on PWI or single-photon emission computed tomography (SPECT) and hypometabolism on FDG-PET and hypointensity on OEF-MRI. Since SLEs are not vascular events, they should be managed by a multispecialist approach and not by general or stroke neurologists.

Localizing a metabolic focus during a functional seizure with fluorodeoxyglucose positron emission tomography-computed tomography.

Traumatic brain injuries can lead to long-term mental seizures that are difficult to differentiate from dissociative psychogenic symptoms, respectively, psychogenic nonepileptic seizures. Recent articles have drawn attention to the need of differentiation of psychological and brain trauma-related symptoms in survivors of violence. This case study reflects a diagnostic step in a 20-year-male who reported to have been subjected to torture, including blunt force to the head 2 years before examination. He suffers from episodical headaches followed by mental bouts of aggression and restlessness. We performed a brain 18F-fluorodeoxyglucose positron emission tomography (PET)-computed tomography to identify a cerebral correlate of the psychogenic seizures. The examination yielded a hypermetabolic focus in the frontal superior parasagittal region. Psychogenic seizures can frequently be observed as culture-specific "idioms of distress" and can challenge diagnostic evaluation, especially in the victims of violence with an additional history of blunt brain trauma. The advances in molecular imaging such as PET can be expected to play a crucial role in forensic and clinical assessment in the increasing number of such patients.

Theranostics of Metastatic Prostate Cancer Applying 64Cu/18F/68Ga PSMA PET-CT and 177Lu Radiopharmaceuticals.

The successful use of theranostic twins in neuroendocrine tumors (NET) is the pioneering approach to radionuclide therapy in other tumor types. 64Cu/18F PSMA for molecular imaging with PET-CT and peptide radioligand therapy (PRLT) with 177Lu labeled PSMA inhibitors are the next theranostic twins in nuclear medicine. 68Ga/ 64Cu/18F PSMA PET-CT detects metastatic prostate cancer with high diagnostic sensitivity and specificity and can be used to select patients for PRLT and evaluate therapy response. Radionuclide therapy with 177Lu-PSMA inhibitors has been shown to be effective in the treatment of metastatic CRPC.

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.

64Cu-DOTATOC PET-CT in Patients with Neuroendocrine Tumors.

INTRODUCTION: Several radiolabeled somatostatin analogues have been developed for molecular imaging of neuroendocrine tumors (NETs) with single-photon emission computed tomography (SPECT) and positron-emission tomography (PET). The aim of the present study was to report our first results using 64Cu-DOTATOC in patients with NETs. METHODS: Thirty-three patients with NETs (15 female, 18 male; mean age 64 ± 13 years) were included in this retrospective study. 64Cu-DOTATOC PET-CT scans were performed on all patients. RESULTS: Five out of 33 patients with a history of NET after surgical removal of the primary lesion showed no pathological lesions on PET-CT imaging and 8/33 patients had enhanced uptake in the area of recurrent meningioma at the skull base. The remaining 20/33 patients had a history of neuroendocrine tumor in the gastrointestinal tract (GEP-NET) and were presented with at least one pathological lesion. CONCLUSION: The high detection rate of suspected lesions in patients with NETs and the high target-to-background contrast found in this study hold promise for the safe application of 64Cu-DOTATOC in patients with NET.

18F-prostate-specific membrane antigen positron emission tomography computed tomography incidental finding in a patient after COVID-19 infection.

The COVID-19 pandemic has now reached most countries. However, the referred patients to a nuclear medicine department will be primarily the asymptomatic ones. We report the case of a patient (84-year-old male) who was sent for18F-prostate-specific membrane antigen positron emission tomography computed tomography (PSMA PET-CT) with suspicion of recurrent disease after prostate cancer and total prostatectomy 2 years prior to the examination. He suffered from COVID-19 pneumonia 4 weeks prior to PET-CT examination. The18F-PSMA PET-CT revealed moderate elevated uptake in the area of previous pneumonia in the right lung. The radiological findings showed ground glass changes in this area indicating possible residual inflammatory disease even weeks after infection.

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.

Bone Scintigraphy in Staging of Newly Diagnosed Prostate Cancer in Regard of Different Risk Groups.

OBJECTIVES: Prostate cancer (PC) is the most common cancer in men over 50 years of age. Bone scintigraphy is still performed in many institutions at the time of primary diagnosis. We aimed to evaluate the role of bone scan in the primary staging of PC in regard of different risk groups. METHODS: A retrospective analysis of bone scans in 296 patients (mean age 64±6 y) acquired at the time of primary diagnosis was performed in our institution. The median prostate specific antigen (PSA) was 6.73 ng/ml, all patients had a Gleason score of >5. RESULTS: Only 11/296 patients had a positive bone scan, 1 being in the intermediate risk group, 10 in the high-risk group and none in the low-risk group according to D'Amico classification. CONCLUSION: Our results support the few published studies that less than 10% of patients with newly diagnosed PC by biopsy would develop bone metastasis, all in the intermediate or high-risk groups. Therefore, a staging by bone scan can only be recommended in patients with intermediate or high-risk, or symptomatic patients only.