Assessing nuclear medicine practices: a critical evaluation of QUANUM through a quality improvement perspective and its wider relevance.

Quality Management Audits in Nuclear Medicine (QUANUM) is an initiative conceived by the International Atomic Energy Agency to enhance global standards in Nuclear Medicine practices. Acknowledging the intricate regulatory frameworks and the necessity for multidisciplinary collaboration, QUANUM has gained global acceptance, demonstrating widespread implementation and positive impacts on patient care. This manuscript critically evaluates the QUANUM program through the lens of quality improvement (QI), by employing established and validated QI tools. Our analysis identifies areas of conformance, underscores key strengths inherent to QUANUM, and pinpoints further learning opportunities for continuous enhancement. Additionally, we assert that the insights derived from scrutinizing this global project within Nuclear Medicine, have valuable implications for departments aspiring for establishing good quality management systems, thereby contributing to the improvement of patient care.

Identifying and troubleshooting the pitfalls of ictal/interictal brain perfusion SPECT studies.

Epilepsy is a prevalent condition, and surgical intervention can benefit patients with refractory seizures. Single photon emission computed tomography (SPECT) using 99mTc-HMPAO or 99mTc-ECD provides assessment of regional cerebral blood flow and is the primary non-invasive approach for imaging brain perfusion in ictal and interictal states. Ictal/interictal SPECT is valuable in localising epileptogenic foci, particularly when MRI and electroencephalography are negative. However, to obtain accurate images reflecting brain perfusion in both states, meticulous preparation of the patient, timely radiotracer injection and close coordination between neurology and nuclear medicine teams are essential. Tracers also have inherent limitations, and patients may present with coexisting brain pathologies for which coregistration of SPECT images with MRI is recommended to improve diagnostic accuracy. Inconclusive SPECT findings may require repeating the exam or considering additional investigations. A comprehensive approach, considering various factors, is crucial for accurate interpretation of SPECT studies in presurgical epilepsy evaluations. This article provides a summary of the organisation and key challenges involved in conducting ictal/interictal SPECT studies, covering the entire process from a patient's hospital arrival to the integration of results within their presurgical pathway and using our experience of 182 patients over 10 years.

Renal protection during 177lutetium DOTATATE molecular radiotherapy in children: a proposal for safe amino acid infusional volume during peptide receptor radionuclide therapy.

Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues such as 177-lutetium DOTATATE is an effective treatment modality for neuroendocrine tumours, paragangliomas, and neuroblastomas. However, renal and haematopoietic toxicities are the major limitations of this therapeutic approach. The renal toxicity of PRRT is mediated by renal proximal tubular reabsorption and interstitial retention of the radiolabelled peptides resulting in excessive renal irradiation that can be dose-limiting. To protect the kidneys from PRRT-induced radiation nephropathy, basic amino acids are infused during PRRT as they competitively bind to the proximal tubular cells and prevent uptake of the radionuclide. In adults, 1 L of a basic amino acid solution consisting of arginine and lysine is infused over 4 h commencing 30 min prior to PRRT. However, this volume of amino acids infused over 4 h is excessive in small children and can result in hemodynamic overload. This is all the more relevant in paediatric oncology, as many of the children may have been heavily pretreated and so may have treatment-related renal and or cardiac impairment. We have therefore developed the following guidelines for safe paediatric dosing of renal protective amino acid infusions during PRRT. Our recommendations have been made taking into consideration the renal physiology in small children and the principles of safe fluid management in children.

The Impact of COVID-19 on Nuclear Medicine in Europe.

The COVID-19 pandemic has profoundly changed hospital activities, including nuclear medicine (NM) practice. This review aimed to determine and describe the impact of COVID-19 on NM in Europe and critically discuss actions and strategies applied to face the pandemic. A literature search for relevant articles was performed on PubMed, covering COVID-19 studies published up until January 21, 2021. The findings were summarized according to general and specific activities within the NM departments. The pandemic strongly challenged NM departments: a reduction in the workforce has been experienced in almost every center in Europe due to personnel diagnosed with COVID-19 and other reasons related to the coronavirus. NM departments introduced procedures to limit COVID-19 transmission, including environmental and personal hygiene, social distancing, rescheduling of non-high-priority procedures, the correct use of personal protective equipment, and prompt identification of suspect COVID-19 cases. A proportion of the departments experienced a delay in radiopharmaceuticals supply or technical assistance during the pandemic. Furthermore, the pandemic resulted in a significant reduction of diagnostic and therapeutic NM procedures, as well as a reduced level of care for patients affected by diseases other than COVID-19, such as cancer or acute cardiovascular disease. Telemedicine services have been set up to maintain medical assistance for patients. COVID-19 pandemic has reshaped human work resources, patient's diagnostic and therapeutic management, operative models, radiopharmaceutical supplies, teaching, training and research of NM departments. Limits of availability of resources emerged. Nonetheless, we have to provide continuity in care, especially for fragile patients, maintaining infection control measures. Challenges that have been faced should reshape our vision and get us prepared for the future.

Distinct Patterns of Brain Metabolism in Patients at Risk of Sudden Unexpected Death in Epilepsy.

Objective: To characterize regional brain metabolic differences in patients at high risk of sudden unexpected death in epilepsy (SUDEP), using fluorine-18-fluorodeoxyglucose positron emission tomography (18FDG-PET). Methods: We studied patients with refractory focal epilepsy at high (n = 56) and low (n = 69) risk of SUDEP who underwent interictal 18FDG-PET as part of their pre-surgical evaluation. Binary SUDEP risk was ascertained by thresholding frequency of focal to bilateral tonic-clonic seizures (FBTCS). A whole brain analysis was employed to explore regional differences in interictal metabolic patterns. We contrasted these findings with regional brain metabolism more directly related to frequency of FBTCS. Results: Regions associated with cardiorespiratory and somatomotor regulation differed in interictal metabolism. In patients at relatively high risk of SUDEP, fluorodeoxyglucose (FDG) uptake was increased in the basal ganglia, ventral diencephalon, midbrain, pons, and deep cerebellar nuclei; uptake was decreased in the left planum temporale. These patterns were distinct from the effect of FBTCS frequency, where increasing frequency was associated with decreased uptake in bilateral medial superior frontal gyri, extending into the left dorsal anterior cingulate cortex. Significance: Regions critical to cardiorespiratory and somatomotor regulation and to recovery from vital challenges show altered interictal metabolic activity in patients with frequent FBTCS considered to be at relatively high-risk of SUDEP, and shed light on the processes that may predispose patients to SUDEP.

Radiomics-Based Texture Analysis of 68Ga-DOTATATE Positron Emission Tomography and Computed Tomography Images as a Prognostic Biomarker in Adults With Neuroendocrine Cancers Treated With 177Lu-DOTATATE.

PURPOSE: Neuroendocrine tumors (NET) are rare cancers with variable behavior. A better understanding of prognosis would aid individualized management. The aim of this hypothesis-generating pilot study was to investigate the prognostic potential of tumor heterogeneity and tracer avidity in NET using texture analysis (TA) of 68Ga-DOTATATE positron emission tomography (PET) and non-enhanced computed tomography (CT) performed at baseline in patients treated with 177Lu-DOTATATE. It aims to justify a larger-scale study to evaluate its clinical value. METHODS: The pretherapy 68Ga-DOTATATE PET-CT scans of 44 patients with metastatic NET (carcinoid, pancreatic, thyroid, head and neck, catecholamine-secreting, and unknown primary NET) treated with 177Lu-DOTATATE were analyzed retrospectively using commercially available texture analysis research software. Image filtration extracted and enhanced objects of different sizes (fine, medium, coarse), then quantified heterogeneity by statistical and histogram-based parameters (mean intensity, standard deviation, entropy, mean of positive pixels, skewness, and kurtosis). Regions of interest were manually drawn around up to five of the most 68Ga-DOTATATE avid lesions for each patient. 68Gallium uptake on PET was quantified as SUVmax and SUVmean. Associations between imaging and clinical markers with progression-free (PFS) and overall survival (OS) were assessed using univariate Kaplan-Meier analysis. Independence of the significant univariate markers of survival was tested using multivariate Cox regression analysis. RESULTS: Measures of heterogeneity (higher kurtosis, higher entropy, and lower skewness) on coarse-texture scale CT and unfiltered PET images predicted shorter PFS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness: p=0.03) and shorter OS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness p=0.02). Conventional PET parameters such as SUVmax and SUVmean showed trends towards predicting outcome but were not statistically significant. Multivariate analysis identified that CT-TA (coarse kurtosis: HR=2.57, 95% CI=1.22-5.38, p=0.013) independently predicted PFS, and PET-TA (unfiltered skewness: HR=9.05, 95% CI=1.19-68.91, p=0.033) independently predicted OS. CONCLUSION: These preliminary data generate a hypothesis that radiomic analysis of neuroendocrine cancer on 68Ga-DOTATATE PET-CT may be of prognostic value and a valuable addition to the assessment of patients.

The value of [68Ga]Ga-DOTA-TATE PET/CT in diagnosis and management of suspected pituitary tumors.

BACKGROUND: Gallium 68-tetraazacyclododecane-tetraacetic acid-octreotate ([68Ga]Ga-DOTA-TATE) is a selective somatostatin analogue ligand, which shows increased affinity for somatostatin receptor subtype (SSTR) 2 and has been used routinely for imaging neuroendocrine tumors with PET/CT. We investigated the utility of [68Ga]Ga-DOTA-TATE positron emission tomography/computed tomography (PET/CT) in patients with suspected pituitary pathology. We reviewed imaging for twenty consecutive patients (8 men, 12 women, mean age of 48.2, range 14-78) with suspected pituitary pathology who were referred for [68Ga]Ga-DOTA-TATE PET/CT. RESULTS: Nine patients presented with recurrent Cushing's syndrome following surgical resection of pituitary adenomas due to recurrent Cushing's disease (seven patients) and ectopic ACTH secreting tumor (2 patients). All seven patients with recurrent Cushing's disease showed positive pituitary [68Ga]Ga-DOTA-TATE uptake while both cases of ectopic hormonal secretion had absented pituitary uptake. In 1 of these 2 patients, [68Ga]Ga-DOTA-TATE was able to localize the source of ectopic ACTH tumor. Six patients presented de novo with Cushing's due to ectopic ACTH secretion; [68Ga]Ga-DOTA-TATE PET/CT was able to localize ectopic tumors in six of eight patients (3 lungs, 2 pancreases, 1 mid-gut) There was high uptake [68Ga]Ga-DOTA-TATE in 3 cases of recurrent central hyperthyroidism (SUVmax 6.6-14.3) and 2 cases of prolactinoma (SUVmax 5.5 and 11.3). CONCLUSION: Absent [68Ga]Ga-DOTA-TATE activity in the pituitary fossa is useful in excluding pituitary disease in recurrent Cushing's. Recurrent pituitary thyrotropinomas and prolactinomas showed moderate to high pituitary activity. In addition, in Cushing's syndrome, [68Ga]Ga-DOTA-TATE is useful for detection of ectopic sources of ACTH production, especially where anatomic imaging is negative.

Personalisation of Molecular Radiotherapy through Optimisation of Theragnostics.

Molecular radiotherapy, or targeted radionuclide therapy, uses systemically administered drugs bearing a suitable radioactive isotope, typically a beta emitter. These are delivered via metabolic or other physiological pathways to cancer cells in greater concentrations than to normal tissues. The absorbed radiation dose in tumour deposits causes chromosomal damage and cell death. A partner radiopharmaceutical, most commonly the same vector labelled with a different radioactive atom, with emissions suitable for gamma camera or positron emission tomography imaging, is used to select patients for treatment and to assess response. The use of these pairs of radio-labelled drugs, one optimised for therapy, the other for diagnostic purposes, is referred to as theragnostics. Theragnostics is increasingly moving away from a fixed number of defined activity administrations, to a much more individualised or personalised approach, with the aim of improving treatment outcomes, and minimising toxicity. There is, however, still significant scope for further progress in that direction. The main tools for personalisation are the following: imaging biomarkers for better patient selection; predictive and post-therapy dosimetry to maximise the radiation dose to the tumour while keeping organs at risk within tolerance limits; imaging for assessment of treatment response; individualised decision making and communication about radiation protection, adjustments for toxicity, inpatient and outpatient care.

68Ga-DOTATATE and 123I-mIBG as imaging biomarkers of disease localisation in metastatic neuroblastoma: implications for molecular radiotherapy.

PURPOSE: Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) and lutetium-177-labelled DOTATATE (Lu-DOTATATE) are used for molecular radiotherapy of metastatic neuroblastoma. These are taken up by the noradrenaline transporter (NAT) and the somatostatin receptor subtype 2 (SSTR-2), respectively. Scintigraphy of iodine-123-labelled meta-iodobenzylguanidine (I-mIBG) and gallium-68 DOTATATE (Ga-DOTATATE) PET are used to select patients for therapy. These demonstrate the extent and location of tumour, and avidity of uptake by cells expressing NAT and SSTR-2, respectively. This study compared the similarities and differences in the anatomical distribution of these two imaging biomarkers in an unselected series of patients with metastatic neuroblastoma undergoing assessment for molecular radiotherapy. METHODS: Paired whole-body planar I-mIBG views and Ga-DOTATATE maximum intensity projection PET scans of metastatic neuroblastoma patients were visually compared. The disease extent was assessed by a semiquantitative scoring method. RESULTS: Paired scans from 42 patients were reviewed. Ga-DOTATATE scans were positive in all patients, I-mIBG scans were negative in two. In two patients, there was a mismatch, with some lesions identified only on the I-mIBG scan, and others visible only on the Ga-DOTATATE scan. CONCLUSION: Ga-DOTATATE and I-mIBG scans yield complementary information. For a more comprehensive assessment, consideration could be given to the use of both I-mIBG and Ga-DOTATATE imaging scans. Because of the heterogeneity of distribution of molecular targets revealed by these techniques, a combination of both I-mIBG and Lu-DOTATATE molecular radiotherapy may possibly be more effective than either alone.

A phase IIa trial of molecular radiotherapy with 177-lutetium DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma.

PURPOSE: The objective of this phase IIa, open-label, single-centre, single-arm, two-stage clinical trial was to evaluate the safety and activity of 177-lutetium DOTATATE (LuDO) molecular radiotherapy in neuroblastoma. METHODS: Children with relapsed or refractory metastatic high-risk neuroblastoma were treated with up to four courses of LuDO. The administered activity was 75 to 100 MBq kg-1 per course, spaced at 8- to 12-week intervals. Outcomes were assessed by the International Neuroblastoma Response Criteria (primary outcome), progression-free survival (PFS), and overall survival (OS). RESULTS: The trial recruited 21 patients; eight received the planned four courses. There was dose-limiting haematologic toxicity in one case, but no other significant haematologic or renal toxicities. None of 14 evaluable patients had an objective response at 1 month after completion of treatment (Wilson 90% CI 0.0, 0.16; and 95% CI is 0.0, 0.22). The trial did not therefore proceed to the second stage. The median PFS was 2.96 months (95% CI 1.71, 7.66), and the median OS was 13.0 months (95% CI 2.99, 21.52). CONCLUSION: In the absence of any objective responses, the use of LuDO as a single agent at the dose schedule used in this study is not recommended for the treatment of neuroblastoma. There are several reasons why this treatment schedule may not have resulted in objective responses, and as other studies do show benefit, the treatment should not be regarded as being of no value. Further trials designed to overcome this schedule's limitations are required. TRIAL REGISTRATION: ISRCTN98918118; URL: https://www.isrctn.com/search?q=98918118.

Diagnosing Dementia in the Clinical Setting: Can Amyloid PET Provide Additional Value Over Cerebrospinal Fluid?

Cerebrospinal fluid (CSF) measures of amyloid and tau are the first-line Alzheimer's disease biomarkers in many clinical centers. We assessed if and when the addition of amyloid PET following CSF measurements provides added diagnostic value. Twenty patients from a cognitive clinic, who had undergone detailed assessment including CSF measures, went on to have amyloid PET. The treating neurologist's working diagnosis, and degree of diagnostic certainty, was assessed both before and after the PET. Amyloid PET changed the diagnosis in 7/20 cases. Amyloid PET can provide added diagnostic value, particularly in young-onset, atypical dementias, where CSF results are borderline and diagnostic uncertainty remains.

Cerebral metabolism and perfusion in MR-negative individuals with refractory focal epilepsy assessed by simultaneous acquisition of (18)F-FDG PET and arterial spin labeling.

The major challenge in pre-surgical epileptic patient evaluation is the correct identification of the seizure onset area, especially in MR-negative patients. In this study, we aimed to: (1) assess the concordance between perfusion, from ASL, and metabolism, from (18)F-FDG, acquired simultaneously on PET/MR; (2) verify the utility of a statistical approach as supportive diagnostic tool for clinical readers. Secondarily, we compared (18)F-FDG PET data from the hybrid PET/MR system with those acquired with PET/CT, with the purpose of validate the reliability of (18)F-FDG PET/MR data. Twenty patients with refractory focal epilepsy, negative MR and a defined electro-clinical diagnosis underwent PET/MR, immediately followed by PET/CT. Standardized uptake value ratio (SUVr) and cerebral blood flow (CBF) maps were calculated for PET/CT-PET/MR and ASL, respectively. For all techniques, z-score of the asymmetry index (zAI) was applied for depicting significant Right/Left differences. SUVr and CBF images were firstly visually assessed by two neuroimaging readers, who then re-assessed them considering zAI for reaching a final diagnosis. High agreement between (18)F-FDG PET/MR and ASL was found, showing hypometabolism and hypoperfusion in the same hemisphere in 18/20 patients, while the remaining were normal. They were completely concordant in 14/18, concordant in at least one lobe in the remaining. zAI maps improved readers' confidence in 12/20 and 15/20 patients for (18)F-FDG PET/MR and ASL, respectively. (18)F-FDG PET/CT-PET/MR showed high agreement, especially when zAI was considered. The simultaneous metabolism-perfusion acquisition provides excellent concordance on focus lateralisation and good concordance on localisation, determining useful complementary information.

Imaging in tuberculosis.

Despite many advances in both diagnosis and treatment, tuberculosis still remains one of commonest causes of morbidity and mortality from any infectious cause in the world. Although the overall incidence and mortality rate for tuberculosis has decreased over the years, timely and accurate diagnosis of tuberculosis is essential for the health of the patient as well as the public. For the diagnosis of tuberculosis, a high degree of clinical suspicion is required, and this becomes much more important in high-risk populations. Tuberculosis may masquerade as any disease; therefore, tissue and microbiological assessment is sometimes important for establishing the diagnosis. However, in daily practice, the clinician and radiologist should be familiar with the imaging features of pulmonary and extrapulmonary tuberculosis, as well as manifestations of tuberculosis in immunocompromised patients. Imaging provides a very important role in the diagnosis and management of tuberculosis. Although chest X rays remain the basic imaging modality for pulmonary tuberculosis, computed tomography, magnetic resonance imaging, and nuclear medicine techniques, including positron emission tomography/computed tomography, are extremely helpful in the assessment of both pulmonary and extrapulmonary tuberculosis.

The use of (68)Ga DOTATATE PET/CT for diagnostic assessment and monitoring of (177)Lu DOTATATE therapy in pituitary carcinoma.

A 68-year-old man, with a history of pituitary surgery and radiation therapy for pituitary macroadenoma 20 years earlier, presented with a pituitary mass and enlarging lesions within the posterior fossa and spinal canal. Biopsy revealed low-grade pituitary carcinoma. PET/CT scan showed multiple foci of increased Ga DOTATATE activity including pituitary and posterior fossa lesions. After 3 fractions of Lu DOTATATE therapy, the tumor remained stable over 4 years on MRI and Ga DOTATATE scans. This case illustrates the benefit of Ga DOTATATE PET/CT in malignant pituitary disease to assess potential for somatostatin receptor therapy with Lu DOTATATE and monitor treatment.

Non-small-cell lung cancer resectability: diagnostic value of PET/MR.

PURPOSE: To assess the diagnostic performance of PET/MR in patients with non-small-cell lung cancer. METHODS: Fifty consecutive consenting patients who underwent routine (18)F-FDG PET/CT for potentially radically treatable lung cancer following a staging CT scan were recruited for PET/MR imaging on the same day. Two experienced readers, unaware of the results with the other modalities, interpreted the PET/MR images independently. Discordances were resolved in consensus. PET/MR TNM staging was compared to surgical staging from thoracotomy as the reference standard in 33 patients. In the remaining 17 nonsurgical patients, TNM was determined based on histology from biopsy, imaging results (CT and PET/CT) and follow-up. ROC curve analysis was used to assess accuracy, sensitivity and specificity of the PET/MR in assessing the surgical resectability of primary tumour. The kappa statistic was used to assess interobserver agreement in the PET/MR TNM staging. Two different readers, without knowledge of the PET/MR findings, subsequently separately reviewed the PET/CT images for TNM staging. The generalized kappa statistic was used to determine intermodality agreement between PET/CT and PET/MR for TNM staging. RESULTS: ROC curve analysis showed that PET/MR had a specificity of 92.3 % and a sensitivity of 97.3 % in the determination of resectability with an AUC of 0.95. Interobserver agreement in PET/MR reading ranged from substantial to perfect between the two readers (Cohen's kappa 0.646 - 1) for T stage, N stage and M stage. Intermodality agreement between PET/CT and PET/MR ranged from substantial to almost perfect for T stage, N stage and M stage (Cohen's kappa 0.627 - 0.823). CONCLUSION: In lung cancer patients PET/MR appears to be a robust technique for preoperative staging.

18F-fluoroethylcholine (18F-Cho) PET/MRI functional parameters in pediatric astrocytic brain tumors.

PURPOSE: To examine the feasibility of simultaneous acquisition of F-fluoroethylcholine (F-choline) PET and functional MRI (standardized uptake value [SUV]max/mean and apparent diffusion coefficient [ADC]mean), using a hybrid PET/MRI scanner, for diagnosis and response assessment in a cohort of children with astrocytic brain tumors. METHODS: F-choline PET/MRI scans were performed in 12 patients with proven astrocytic tumors.Eight patients simultaneously underwent F-choline PET/MR follow-up scans after treatment. Uptake in the lesion above the normal brain activity was considered indicative of a positive scan. Maximum and mean SUVs (SUVmax and SUVmean) and mean ADC (ADCmean) of the whole tumor region of interest were assessed. Lesion size and contrast enhancement were recorded. For all tumors, the association between ADCmean and SUVmean/SUVmax values were assessed using the Spearman correlation coefficient. RESULTS: At baseline, the areas of F-choline uptake matched areas of contrast enhancement and restricted diffusion. There was a negative correlation trend between SUVmax and ADCmean and a positive correlation trend between SUVmax and tumor size. There was concordance between reduction in tumor size and reductions in SUVmax and SUVmean in 4 children, in three of whom ADCmean values were increased. In 2 patients, tumor size remained stable whereas SUVmax and SUVmean values were increased with reduction in the ADCmean values. Additionally, in 2 children, cross-sectional MRI showed an increase both in tumor size and SUVmax but a reduction in ADC values. CONCLUSIONS: Simultaneous F-choline PET/MRI is a promising and reliable imaging tool for children with astrocytic tumors, as it permits monitoring of morphological and metabolic response and changes during therapy.