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Hybrid devices are increasingly used in nuclear medicine diagnostics. They enable molecular imaging (single photon emission computerized tomography – SPECT) of pathological changes in the body. It is necessary to refine the parameters of image acquisition and reconstruction, as well as to formulate clinical recommendations for hybrid SPECT/computed tomography (CT) examinations. Therefore, this study aimed to investigate the diagnostic usefulness of SPECT/CT examinations using a hybrid gamma camera, with particular emphasis on skeletal scintigraphy. This work attempts to address this question.

The present article highlights the important progress made in the last two decades in the fields of molecular imaging and radionuclide therapy. Advancements in radiometal-based positron emission tomography, single photon emission computerized tomography, and radionuclide therapy are illustrated in terms of their production routes and ease of radiolabeling. Applications in clinical diagnostic and radionuclide therapy are considered, including human studies under clinical trials; their current stages of clinical translations and findings are summarized. Because the metalloid astatine is used for imaging and radionuclide therapy, it is included in this review. In regard to radionuclide therapy, both beta-minus (β−) and alpha (α)-emitting radionuclides are discussed by highlighting their production routes, targeted radiopharmaceuticals, and current clinical translation stage.

Purpose The primary purpose of this retrospective study with prospectively collected data was to evaluate the clinical value of SPECT/CT, in particular its impact on clinical diagnosis and patient management, in patients with pain, stiffness, or swelling after primary total knee arthroplasty (TKA). The secondary purpose was to determine the sensitivity and the specificity of SPECT/CT for different pathologies such as loosening and patellofemoral overloading. Methods A retrospective analysis was carried out on 214 knees in 202 consecutive patients (mean age 69 ± 11 years) with persistent or recurrent knee pain after TKA. All patients underwent clinical examination, standardised radiographs, and 99mTc-hydroxymethane diphosphonate (HDP) SPECT/CT as part of a routine diagnostic algorithm. The diagnoses before and after SPECT/CT and final treatment were recorded. TKA component position was routinely measured on 3D-reconstructed images. Intensity and anatomical distribution of bone tracer uptake were determined. Results SPECT/CT changed the clinical diagnosis and final treatment in 139/214 (65%) knees. In 117 (54.7%) out of 214 patients, revision surgery was proposed following SPECT/CT. Early onset of pain was significantly ( p  = 0.011) correlated with tibiofemoral stress pattern in SPECT/CT. A total of 86 knees (40.2%) were surgically revised using semi-constrained or fully constrained TKA. In 35 patients, a secondary patellar resurfacing was performed. SPECT/CT showed the clinical diagnosis to be incorrect for suspicion of tibial component loosening in 56 patients (26.2%), femoral component loosening in 53 patients (24.8%), and patellofemoral overloading/progressive patellofemoral osteoarthritis in 26 patients (12.1%) and provided different underlying causes of persistent knee pain after TKA. Likewise, SPECT/CT identified tibial component loosening in 8 patients (3.7%), femoral component loosening in 4 patients (1.9%), and patellofemoral OA in 71 patients (33.2%) without prior clinical suspected diagnosis. The sensitivity and specificity of SPECT/CT for detection of patellofemoral OA was 96.5% and 96.2%, respectively. The sensitivity and specificity for detection of tibial component loosening was 96.0% and 100%, respectively. The sensitivity and specificity for detection of femoral component loosening was 95.0% and 100%, respectively. Conclusion The diagnostic benefits of SPECT/CT in the challenging and complex cohort of patients with pain after primary TKA have been proven. The excellent sensitivity and specificity for detection of tibial or femoral component loosening and diagnosis of patellofemoral OA have been surgically confirmed. Due to the benefits in establishing the correct diagnosis, SPECT/CT should be implemented as part of the routine diagnostic algorithm for patients with pain after primary TKA. Level of evidence II.

Although promising responses are obtained in patients treated with immune checkpoint inhibitors targeting programmed death ligand 1 (PD-L1) and its receptor programmed death-1 (PD-1), only a fraction of patients benefits from this immunotherapy. Cancer vaccination may be an effective approach to improve the response to immune checkpoint inhibitors anti-PD-L1/PD-1 therapy. However, there is a lack of research on the dynamics of PD-L1 expression in response to cancer vaccination. We performed non-invasive whole-body imaging to visualize PD-L1 expression at different timepoints after vaccination of melanoma-bearing mice. Mice bearing ovalbumin (OVA) expressing B16 tumors were i.v. injected with the Galsome mRNA vaccine: OVA encoding mRNA lipoplexes co-encapsulating a low or a high dose of the atypical adjuvant α-galactosylceramide (αGC) to activate invariant natural killer T (iNKT) cells. Serial non-invasive whole-body immune imaging was performed using a technetium-99m ( Tc)-labeled anti-PD-L1 nanobody, single-photon emission computerized tomography (SPECT) and X-ray computed tomography (CT) images were quantified. Additionally, cellular expression of PD-L1 was evaluated with flow cytometry. SPECT/CT-imaging showed a rapid and systemic upregulation of PD-L1 after vaccination. PD-L1 expression could not be correlated to the αGC-dose, although we observed a dose-dependent iNKT cell activation. Dynamics of PD-L1 expression were organ-dependent and most pronounced in lungs and liver, organs to which the vaccine was distributed. PD-L1 expression in lungs increased immediately after vaccination and gradually decreased over time, whereas in liver, vaccination-induced PD-L1 upregulation was short-lived. Flow cytometric analysis of these organs further showed myeloid cells as well as non-immune cells with elevated PD-L1 expression in response to vaccination. SPECT/CT imaging of the tumor demonstrated that the expression of PD-L1 remained stable over time and was overall not affected by vaccination although flow cytometric analysis at the cellular level demonstrated changes in PD-L1 expression in various immune cell populations following vaccination. Repeated non-invasive whole-body imaging using Tc-labeled anti-PD-L1 nanobodies allows to document the dynamic nature of PD-L1 expression upon vaccination. Galsome vaccination rapidly induced systemic upregulation of PD-L1 expression with the most pronounced upregulation in lungs and liver while flow cytometry analysis showed upregulation of PD-L1 in the tumor microenvironment. This study shows that imaging using nanobodies may be useful for monitoring vaccine-mediated PD-L1 modulation in patients and could provide a rationale for combination therapy. To the best of our knowledge, this is the first report that visualizes PD-L1 expression upon cancer vaccination.

Peripheral artery disease (PAD) is a common and debilitating condition characterized by the narrowing of the limb arteries, primarily due to atherosclerosis. Non-invasive multi-modality imaging approaches using computed tomography (CT), magnetic resonance imaging (MRI), and nuclear imaging have emerged as valuable tools for assessing PAD atheromatous plaques and vessel walls. This review provides an overview of these different imaging techniques, their advantages, limitations, and recent advancements. In addition, this review highlights the importance of molecular markers, including those related to inflammation, endothelial dysfunction, and oxidative stress, in PAD pathophysiology. The potential of integrating molecular and imaging markers for an improved understanding of PAD is also discussed. Despite the promise of this integrative approach, there remain several challenges, including technical limitations in imaging modalities and the need for novel molecular marker discovery and validation. Addressing these challenges and embracing future directions in the field will be essential for maximizing the potential of molecular and imaging markers for improving PAD patient outcomes.

In last years, several approaches to develop an effective Computer-Aided-Diagnosis (CAD) system for Parkinson's Disease (PD) have been proposed. Most of these methods have focused almost exclusively on brain images through the use of Machine-Learning algorithms suitable to characterize structural or functional patterns. Those patterns provide enough information about the status and/or the progression at intermediate and advanced stages of Parkinson's Disease. Nevertheless this information could be insufficient at early stages of the pathology. The Parkinson's Progression Markers Initiative (PPMI) database includes neurological images along with multiple biomedical tests. This information opens up the possibility of comparing different biomarker classification results. As data come from heterogeneous sources, it is expected that we could include some of these biomarkers in order to obtain new information about the pathology. Based on that idea, this work presents an Ensemble Classification model with Performance Weighting. This proposal has been tested comparing Healthy Control subjects (HC) vs. patients with PD (considering both PD and SWEDD labeled subjects as the same class). This model combines several Support-Vector-Machine (SVM) with linear kernel classifiers for different biomedical group of tests-including CerebroSpinal Fluid (CSF), RNA, and Serum tests-and pre-processed neuroimages features (Voxels-As-Features and a list of defined Morphological Features) from PPMI database subjects. The proposed methodology makes use of all data sources and selects the most discriminant features (mainly from neuroimages). Using this performance-weighted ensemble classification model, classification results up to 96% were obtained.

Investigate the effect of acupuncture on brain perfusion using ethyl cysteinate dimer single-photon emission computed tomography ((99m)Tc-ECD SPECT) in patients with tinnitus. This randomized, single-blind, sham-control study examined patients (18-60 years old) with normal hearing and chronic, idiopathic, continuous tinnitus. Fifty-seven subjects were randomly assigned to true (n = 30) or sham (n = 27) acupuncture (ACP); (99m)Tc-ECD SPECT examinations were performed before and after 12 twice-weekly ACP sessions. Secondary outcomes included changes in the Tinnitus Handicap Inventory (THI), Visual Analog Scale (VAS), Hamilton Anxiety Scale (HAS) and Beck Depression Inventory (BDI). Imaging data were analysed using Statistical Parametric Mapping (SPM8) software. Regression models were used to examine secondary outcomes via two paradigms: intention-to-treat (ITT; where multiple imputations were conducted because of study attrition) and complete cases. No between-group brain perfusion differences were observed. However, a significant improvement in THI scores was observed at the end of true ACP treatment for all domains (all p values < 0.01) except the catastrophic scale. ACP might reduce the effects of tinnitus on daily life; however, additional studies should be conducted to verify the effects of ACP on the neural architecture and brain function of tinnitus patients. • Efficacy of acupuncture on brain perfusion and symptoms of tinnitus patients. • Acupuncture improved the Tinnitus Handicap Inventory scores in tinnitus patients. • No significant changes in brain perfusion were observed after 12 twice-weekly sessions. • Perfusion changes would reflect changes in neuronal function.

Differential diagnosis between Parkinson's disease (PD) Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), namely spectrum of Lewy bodies disorders (LBDs), may be challenging, and their common underlying pathophysiology is debated. Our aim was to examine relationships among neurodegenerative biomarkers [alpha-synuclein (α-Syn), Alzheimer’s Disease (AD)—related (beta‐amyloid Aβ 42 , tau [total τ Τ and phosphorylated τ p−181 ]), dopaminergic imaging (DATSCAN–SPECT)] and spectrum of LBD. This is a cross‐sectional prospective study in 30 PD, 18 PDD, 29 DLB patients and 30 healthy controls. We compared α‐Syn in CSF, plasma and serum and CSF Aβ 42 , τ Τ and τ p−181 across these groups. Correlations between such biomarkers and motor, cognitive/neuropsychiatric tests, and striatal asymmetry indexes were examined. CSF α-Syn was higher in DLB versus PD/PDD/controls, and lower in PD and PDD patients compared to controls (all p  < 0.001). Serum α-Syn levels were higher in all patient groups compared to controls. After excluding those DLB patients with CSF AD profile, plasma and serum Syn levels were higher in the LBD group as a whole compared to controls. The combination of CSF α-Syn, serum α-Syn and Aβ 42 for comparison between PD and DLB [AUC = 0.96 (95% CI 0.90–1.00)] was significantly better when compared to serum α-Syn alone ( p  < 0.001). Correlation analyses of biomarkers with cognitive/neuropsychiatric scales revealed some associations, but no consistent, cohesive picture. Peripheral biomarkers such as serum α-Syn, and CSF α-Syn and Aβ 42 may contribute as potential biomarkers to separate LBDs from controls and to differentiate DLB from the other LBDs with high sensitivity and specificity among study groups.

Purpose The primary purpose of this study was to compare bone tracer uptake (BTU) on SPECT/CT in symptomatic and asymptomatic total hip arthroplasty (THA) and identify a possible relationship between BTU patterns and patient’s symptoms. The secondary purpose was to investigate if the fixation methods (cemented versus uncemented) lead to different BTU patterns. Methods A total of 58 THAs, 31 symptomatic (group S) and 27 asymptomatic (group AS), were prospectively collected and retrospectively analyzed. All symptomatic patients underwent standardized detailed history, clinical examination, radiographs and 99mTc-HDP SPECT/CT. BTU in SPECT/CT was quantified in three dimensions and anatomically localized in a scheme of quadrants and levels using a customized previously validated software. T tests were used on both quadrants and levels inside and between groups. A Pearson correlation was performed for BTU within the quadrants. An area under receiver operating characteristic curves was drawn in order to find a BTU value that could differentiate the two groups. Within the groups, patients with cemented and uncemented stems were compared for influences on BTU intensity. Results The causes of pain were identified in 61% of the patients. The most common problem was aseptic loosening ( n  = 12). In group AS, levels 1, 2 and 5 had similar BTUs. BTUs in these levels were significantly higher than in level 3, 4 and 6. In group S, no significant differences were seen in terms of BTU in level 1–5. However, BTU here was significantly higher than at level 6 ( p  < 0.001). In both groups, level 1, the superior, had a significantly higher BTU than level 2 (group AS p  < 0.01, group S p  < 0.05). Comparing the BTU of the two groups among levels, significant differences were found for level 4, level 5 and the entire stem areas ( p  < 0.05). The ROC curve calculated on the whole stem allowed identification of a BTU ratio of 3.1 that separated the 92.6% patients of group AS with BTU < 3.1 from the 54.8% of patients of group S with a BTU ≥ 3.1. With regards to the fixation technique, only the BTU at the level 6 in group S presented a significant difference between cemented and uncemented stems ( p  < 0.05). Conclusions Higher BTU levels significantly correlated with symptoms, but a normal BTU could not exclude a specific pathology after THA. A threshold of BTU in SPECT/CT was identified to distinguish between symptomatic and asymptomatic patients after THA.

Background Several lipid metabolites in cerebrospinal fluid are correlated with poor outcomes in aneurysmal subarachnoid haemorrhage. Most of these metabolites bind to ubiquitous thromboxane–prostaglandin (TP) receptors, causing vasoconstriction and inflammation. Here, we evaluated terutroban (TBN), a specific TP receptor antagonist, for the prevention of post-haemorrhage blood-brain barrier disruption, neuronal apoptosis and delayed cerebral hypoperfusion. Methods The rat double subarachnoid haemorrhage model was produced by twice injecting (days 1 and 2) autologous blood into the cisterna magna. Seventy-eight male Sprague-Dawley rats were assigned to experimental groups. Rats exposed to subarachnoid haemorrhage were allocated to no treatment (SAH group) or TBN treatment by gastric gavage during the first 5 days after haemorrhage (SAH+TBN group). Control rats received artificial cerebrospinal fluid injections (CSF group). Sham-operated rats with or without TBN administration were also studied. Body weight and Garcia neurological scores were assessed on day 2 and day 5. We used nanoscale single-photon emission computed tomography (nanoSPECT) to measure brain uptake of three radiolabelled agents: 99m Technetium-diethylenetriaminepentacetate ( 99m Tc-DTPA), which indicated blood-brain barrier permeability on day 3, 99m Technetium-annexin V-128 ( 99m Tc-Anx-V128), which indicated apoptosis on day 4, and 99m Technetium-hexamethylpropyleneamineoxime ( 99m Tc-HMPAO), which indicated cerebral perfusion on day 5. Basilar artery narrowing was verified histologically, and cerebral TP receptor agonists were quantified. Results 99m Tc-DTPA uptake unveiled blood-brain barrier disruption in the SAH group. TBN mitigated this disruption in the brainstem area. 99m Tc-Anx-V128 uptake was increased in the SAH group and TBN diminished this effect in the cerebellum. 99m Tc-HMPAO uptake revealed a global decreased perfusion on day 5 in the SAH group that was significantly counteracted by TBN. TBN also mitigated basilar artery vasoconstriction, neurological deficits (on day 2), body weight loss (on day 5) and cerebral production of vasoconstrictors such as Thromboxane B2 and Prostaglandin F2α. Conclusions Based on in vivo nanoscale imaging, we demonstrated that TBN protected against blood-brain barrier disruption, exerted an anti-apoptotic effect and improved cerebral perfusion. Thus, TP receptor antagonists showed promising results in treating post-haemorrhage neurovascular events.