Asunto(s)

Estenosis de la Válvula Aórtica , Humanos , Estenosis de la Válvula Aórtica/cirugía

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Conventionally, transrectal ultrasound guided prostate biopsy (TRUS-Bx) was the main technique used for the diagnosis of prostate cancer since it was first described in 1989 [1]. However, the PROMIS trial showed that this random, nontargeted approach could miss up to 18% of clinically significant cancer (csPCa) [2]. Furthermore, risk of sepsis post TRUS-Bx can be as high as 2.4% [3]. Understanding the demerits of TR-biopsy have led to the introduction of transperineal prostate biopsy (TP-Bx). The incorporation of mpMRI revolutionized prostate cancer diagnostics, allowing visualization of areas likely to harbor csPCa whilst permitting some men to avoid an immediate biopsy. Furthermore, the advent of prostate specific membrane antigen-positron emission tomography (PSMA-PET) is highly promising, because of its role in primary diagnosis of prostate cancer and its higher diagnostic accuracy over conventional imaging in detecting nodal and metastatic lesions. Our narrative review provides an overview on prostate biopsy techniques and an update on prostate imaging, with particular focus on PSMA-PET.

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PURPOSE: Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells (PC) in the bone marrow (BM). B-cell maturation antigen (BCMA) is predominantly expressed in malignant plasma cells, and associated with the proliferation, survival, and progression of various myeloma cells. Given these important roles, BCMA emerges as an ideal target antigen for MM therapy. However, effective stratification of patients who may benefit from targeted BCMA therapy and real-time monitoring the therapeutic efficacy poses significant clinical challenge. This study aims to develop a BCMA targeted diagnostic modality, and preliminarily explore its potential value in the radio-immunotherapy of MM. EXPERIMENTAL DESIGN: Using zirconium-89 (89Zr, t1/2 = 78.4 h) for labeling the BCMA-specific antibody, the BCMA-targeting PET tracer [89Zr]Zr-DFO-BCMAh230430 was prepared. The EC50 values of BCMAh230430 and DFO-BCMAh230430 were determined by ELISA assay. BCMA expression was assessed in four different tumor cell lines (MM.1S, RPMI 8226, BxPC-3, and KYSE520) through Western blot and flow cytometry. In vitro binding affinity was determined by cell uptake studies of [89Zr]Zr-DFO-BCMAh230430 in these tumor cell lines. For in vivo evaluation, PET imaging and ex vivo biodistribution studies were conducted in tumor-bearing mice to evaluate imaging performance and systemic distribution of [89Zr]Zr-DFO-BCMAh230430. Immunochemistry analysis was performed to detect BCMA expression in tumor tissues, confirming the specificity of our probe. Furthermore, we explored the anti-tumor efficacy of Lutetium-177 labeled BCMA antibody, [177Lu]Lu-DTPA-BCMAh230430, in tumor bearing-mice to validate its radioimmunotherapy potential. RESULTS: The radiolabeling of [89Zr]Zr-DFO-BCMAh230430 and [177Lu]Lu-DTPA-BCMAh230430 showed satisfactory radiocharacteristics, with a radiochemical purity exceeding 99%. ELISA assay results revealed closely aligned EC50 values for BCMAh230430 and DFO-BCMAh230430, which are 57 pM and 67 pM, respectively. Western blot and flow cytometry analyses confirmed the highest BCMA expression level. Cell uptake data indicated that MM.1S cells had a total cellular uptake (the sum of internalization and surface binding) of 38.3% ± 1.53% for [89Zr]Zr-DFO-BCMAh230430 at 12 h. PET imaging of [89Zr]Zr-DFO-BCMAh230430 displayed radioactive uptake of 7.71 ± 0.67%ID/g in MM.1S tumors and 4.13 ± 1.21%ID/g in KYSE520 tumors at 168 h post-injection (n = 4) (P < 0.05), consistent with ex vivo biodistribution studies. Immunohistochemical analysis of tumor tissues confirmed higher BCMA expression in MM.1S tumors xenograft compared to KYSE520 tumors. Notably, [177Lu]Lu-DTPA-BCMAh230430 showed some anti-tumor efficacy, evidenced by slowed tumor growth. Furthermore, no significant difference in body weight was observed in MM.1S tumor-bearing mice over 14 days of administration with or without [177Lu]Lu-DTPA-BCMAh230430. CONCLUSIONS: Our study has successfully validated the essential role of [89Zr]Zr-DFO-BCMAh230430 in non-invasively monitoring BCMA status in MM tumors, showing favorable tumor uptake and specific binding affinity to MM tumors. Furthermore, our research revealed, as a proof-of-concept, the effectiveness of [177Lu]Lu-DTPA-BCMAh230430 in radioimmunotherapy for MM tumors. In conclusion, we present a novel BCMA antibody-based radiotheranostic modality that holds promise for achieving efficient and precise MM diagnostic and therapy.

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This systematic review aimed to evaluate the potential of deep learning algorithms for converting low-dose Positron Emission Tomography (PET) images to full-dose PET images in different body regions. A total of 55 articles published between 2017 and 2023 by searching PubMed, Web of Science, Scopus and IEEE databases were included in this review, which utilized various deep learning models, such as generative adversarial networks and UNET, to synthesize high-quality PET images. The studies involved different datasets, image preprocessing techniques, input data types, and loss functions. The evaluation of the generated PET images was conducted using both quantitative and qualitative methods, including physician evaluations and various denoising techniques. The findings of this review suggest that deep learning algorithms have promising potential in generating high-quality PET images from low-dose PET images, which can be useful in clinical practice.

Asunto(s)

Aprendizaje Profundo , Tomografía de Emisión de Positrones , Dosis de Radiación , Humanos , Tomografía de Emisión de Positrones/métodos , Procesamiento de Imagen Asistido por Computador/métodos

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A new type of hybrid polymer particles capable of carrying the cytostatic drug doxorubicin and labeled with a gallium compound was prepared. These microparticles consist of a core and a hydrogel shell, which serves as the structural matrix. The shell can be employed to immobilize gallium oxide hydroxide (GaOOH) nanoparticles and the drug, resulting in hybrid beads with sizes of approximately 3.81 ± 0.09 µm. The microparticles exhibit the ability to incorporate a remarkably large amount of doxorubicin, approximately 0.96 mg per 1 mg of the polymeric carrier. Additionally, GaOOH nanoparticles can be deposited within the hydrogel layer at an amount of 0.64 mg per 1 mg of the carrier. These nanoparticles, resembling rice grains with an average size of 593 nm by 155 nm, are located on the surface of the polymer carrier. In vitro studies on breast and colon cancer cell lines revealed a pronounced cytotoxic effect of the hybrid polymer particles loaded with doxorubicin, indicating their potential for cancer therapies. Furthermore, investigations on doping the hybrid particles with the Ga-68 radioisotope demonstrated their potential application in positron emission tomography (PET) imaging. The proposed structures present a promising theranostic platform, where particles could be employed in anticancer therapies while monitoring their accumulation in the body using PET.

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Doxorrubicina , Galio , Hidrogeles , Nanopartículas , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/administración & dosificación , Humanos , Galio/química , Nanopartículas/química , Hidrogeles/química , Portadores de Fármacos/química , Línea Celular Tumoral , Radioisótopos de Galio/química , Tomografía de Emisión de Positrones , Hidróxidos/química , Supervivencia Celular/efectos de los fármacos , Tamaño de la Partícula

RESUMEN

The aim of this study is to estimate eye lens exposure dose when handling radiopharmaceuticals and interacting with patients receiving radiopharmaceuticals, and to verify the usefulness of X-ray protective goggles in mitigating such radiation exposure using phantoms. To evaluate radiation exposure during the handling of radiopharmaceuticals, we employed a fluorescent glass dosimeter to measure the radiation doses associated with 99mTc, 123I, 131I, 111In, and 18F at distances of 30 cm and 60 cm, followed by calculation of the 3 mm dose equivalent rate (3DER). We then estimated the dose reduction rates for various scenarios, including the use of syringe shields and X-ray protective goggles with lead equivalences of 0.07, 0.15, 0.75, and 0.88 mmPb, as well as their combined application. X-ray protective goggles with lead equivalence of 0.75 mmPb outperformed those with 0.07 mmPb and 0.15 mmPb, for all radionuclides and at both source distances. X-ray protective goggles with 0.88 mmPb outperformed those with 0.75 mmPb during handling of 131I and 111In at a distance of 30 cm. In the remaining scenarios, X-ray protective goggles with 0.88 mmPb resulted in marginal reductions or no discernible additional effects. The overall shielding effect of X-ray protective goggles was less pronounced for 131I and 18F, but the combined use of a syringe shield with X-ray protective goggles with 0.75 or 0.88 mmPb improved the dose reduction rate for all scenarios. In simulating patient care, X-ray protective goggles with 0.88 mmPb demonstrated a dose reduction effect of approximately 50% or more. X-ray protective goggles could reduce the 3DER for the eye lens, and were more effective when combined with a syringe shield. It is valid to use a lead equivalence of 0.88 mmPb to fully harness the protective capabilities of X-ray shielding goggles when dealing with all five types of nuclides in clinical settings.

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One of the pathologic hallmarks of Alzheimer's disease (AD) is neurofibrillary tau tangles. Despite our knowledge that tau typically initiates in the medial temporal lobe (MTL), the mechanisms driving tau to spread beyond MTL remain unclear. Emerging evidence reveals distinct patterns of functional connectivity change during aging and preclinical AD: while connectivity within-network decreases, connectivity between-network increases. Building upon increased between-network connectivity, our study hypothesizes that this increase may play a critical role in facilitating tau spread in early stages. We conducted a longitudinal study over two to three years intervals on a cohort of 46 healthy elderly participants (mean age 64.23 ± 3.15 years, 26 females). Subjects were examined clinically and utilizing advanced imaging techniques that included resting-state functional MRI (rs-fMRI), structural magnetic resonance imaging (MRI), and a second-generation positron emission tomography (PET) tau tracer, 18F-MK6240. Through unsupervised agglomerative clustering and increase in between-network connectivity, we successfully identified individuals at increased risk of future tau elevation and AD progression. Our analysis revealed that individuals with increased between-network connectivity are more likely to experience more future tau deposition, entorhinal cortex thinning, and lower selective reminding test (SRT) delayed scores. Additionally, in the limbic network, we found a strong association between tau progression and increased between-network connectivity, which was mainly driven by beta-amyloid (Aß) positive participants. These findings provide evidence for the hypothesis that an increase in between-network connectivity predicts future tau deposition and AD progression, also enhancing our understanding of AD pathogenesis in the preclinical stages.

Asunto(s)

Enfermedad de Alzheimer , Progresión de la Enfermedad , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Proteínas tau , Humanos , Femenino , Masculino , Proteínas tau/metabolismo , Anciano , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Tomografía de Emisión de Positrones/métodos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Estudios Longitudinales , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/patología , Factores de Riesgo , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/metabolismo , Red Nerviosa/patología , Red Nerviosa/fisiopatología

RESUMEN

INTRODUCTION: We disclosed amyloid positron emission tomography (PET) results in individuals with subjective cognitive decline (SCD) and studied patient experiences and outcomes over a 6-month period. METHODS: Fifty-seven participants from the Subjective Cognitive Impairment Cohort (SCIENCe) (66 ± 8 years, 21 [37%] F, Mini-Mental State Examination 29 ± 1, 15 [26%] amyloid positive [A+]) completed questionnaires 1 week prior (T0), 1 day after (T1), and 6 months after amyloid PET disclosure (T2). Questionnaires addressed patient-reported experiences and outcomes. RESULTS: Independent of amyloid status, participants were satisfied with the consultation (scale 1-10; 7.9 ± 1.7) and information provided (scale 1-4; T1: 3.3 ± 0.9, T2: 3.2 ± 0.8). After 6 months, A+ participants reported more information needs (45% vs. 12%, p = 0.02). Independent of amyloid status, decision regret (scale 1-5; A+: 1.5 ± 0.9, A-: 1.4 ± 0.6, p = 0.53) and negative emotions (negative affect, uncertainty, anxiety) were low (all p > 0.15 and Pinteraction > 0.60). DISCUSSION: Participants with SCD valued amyloid PET disclosure positively, regardless of amyloid status. The need for information after 6 months, which was stronger in A+ individuals, underscores the importance of follow-up. HIGHLIGHTS: Participants with subjective cognitive decline (SCD) positively valued amyloid positron emission tomography (PET) disclosure. Participants with SCD experienced low levels of decision regret. We did not observe an increase in negative emotions. After 6 months, amyloid-positive individuals wanted more information.

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BACKGROUND: Accurately redirecting reconstructed Positron emission tomography (PET) images into short-axis (SA) images shows great significance for subsequent clinical diagnosis. We developed a system for automatic redirection and quantitative analysis of myocardial PET images. METHODS: A total of 128 patients were enrolled for 18 F-FDG PET/CT myocardial metabolic images (MMIs), including 3 image classifications: without defects, with defects, and excess uptake. The automatic reorientation system includes five modules: regional division, myocardial segmentation, ellipsoid fitting, image rotation and quantitative analysis. First, the left ventricular geometry-based canny edge detection (LVG-CED) was developed and compared with the other 5 common region segmentation algorithms, the optimized partitioning was determined based on partition success rate. Then, 9 myocardial segmentation methods and 4 ellipsoid fitting methods were combined to derive 36 cross combinations for diagnostic performance in terms of Pearson correlation coefficient (PCC), Kendall correlation coefficient (KCC), Spearman correlation coefficient (SCC), and determination coefficient. Finally, the deflection angles were computed by ellipsoid fitting and the SA images were derived by affine transformation. Furthermore, the polar maps were used for quantitative analysis of SA images, and the redirection effects of 3 different image classifications were analyzed using correlation coefficients. RESULTS: On the dataset, LVG-CED outperformed other methods in the regional division module with a 100% success rate. In 36 cross combinations, PSO-FCM and LLS-SVD performed the best in terms of correlation coefficient. The linear results indicate that our algorithm (LVG-CED, PSO-FCM, and LLS-SVD) has good consistency with the reference manual method. In quantitative analysis, the similarities between our method and the reference manual method were higher than 96% at 17 segments. Moreover, our method demonstrated excellent performance in all 3 image classifications. CONCLUSION: Our algorithm system could realize accurate automatic reorientation and quantitative analysis of PET MMIs, which is also effective for images suffering from interference.

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Deep learning, particularly convolutional neural networks (CNNs), has advanced positron emission tomography (PET) image reconstruction. However, it requires extensive, high-quality training datasets. Unsupervised learning methods, such as deep image prior (DIP), have shown promise for PET image reconstruction. Although DIP-based PET image reconstruction methods demonstrate superior performance, they involve highly time-consuming calculations. This study proposed a two-step optimization method to accelerate end-to-end DIP-based PET image reconstruction and improve PET image quality. The proposed two-step method comprised a pre-training step using conditional DIP denoising, followed by an end-to-end reconstruction step with fine-tuning. Evaluations using Monte Carlo simulation data demonstrated that the proposed two-step method significantly reduced the computation time and improved the image quality, thereby rendering it a practical and efficient approach for end-to-end DIP-based PET image reconstruction.

Asunto(s)

Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador , Método de Montecarlo , Tomografía de Emisión de Positrones , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía de Emisión de Positrones/métodos , Humanos , Fantasmas de Imagen

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Stimulants represent the first line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) and are among the most prescribed psychopharmacological treatments. Their mechanism of action at synaptic level has been extensively studied. However, it is less clear how their mechanism of action determines clinically observed benefits. To help bridge this gap, we provide a comprehensive review of stimulant effects, with an emphasis on nuclear medicine and magnetic resonance imaging (MRI) findings. There is evidence that stimulant-induced modulation of dopamine and norepinephrine neurotransmission optimizes engagement of task-related brain networks, increases perceived saliency, and reduces interference from the default mode network. An acute administration of stimulants may reduce brain alterations observed in untreated individuals in fronto-striato-parieto-cerebellar networks during tasks or at rest. Potential effects of prolonged treatment remain controversial. Overall, neuroimaging has fostered understanding on stimulant mechanism of action. However, studies are often limited by small samples, short or no follow-up, and methodological heterogeneity. Future studies should address age-related and longer-term effects, potential differences among stimulants, and predictors of treatment response.

Asunto(s)

Trastorno por Déficit de Atención con Hiperactividad , Encéfalo , Estimulantes del Sistema Nervioso Central , Red Nerviosa , Humanos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Estimulantes del Sistema Nervioso Central/farmacología , Encéfalo/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/fisiopatología , Red Nerviosa/efectos de los fármacos , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Neuronas/efectos de los fármacos

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Prostate cancer represents a significant public health challenge, with its management requiring precise diagnostic and prognostic tools. Prostate-specific membrane antigen (PSMA), a cell surface enzyme overexpressed in prostate cancer cells, has emerged as a pivotal biomarker. PSMA's ability to increase the sensitivity of PET imaging has revolutionized its application in the clinical management of prostate cancer. The advancements in PET-PSMA imaging technologies and methodologies, including the development of PSMA-targeted radiotracers and optimized imaging protocols, led to diagnostic accuracy and clinical utility across different stages of prostate cancer. This highlights its superiority in staging and its comparative effectiveness against conventional imaging modalities. This paper analyzes the impact of PET-PSMA on prostate cancer management, discussing the existing challenges and suggesting future research directions. The integration of recent studies and reviews underscores the evolving understanding of PET-PSMA imaging, marking its significant but still expanding role in clinical practice. This comprehensive review serves as a crucial resource for clinicians and researchers involved in the multifaceted domains of prostate cancer diagnosis, treatment, and management.

Asunto(s)

Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Pronóstico , Glutamato Carboxipeptidasa II , Antígenos de Superficie , Biomarcadores de Tumor

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Positron Emission Tomography (PET) is a powerful medical imaging technique widely used for detection and monitoring of disease. However, PET imaging can be adversely affected by patient motion, leading to degraded image quality and diagnostic capability. Hence, motion gating schemes have been developed to monitor various motion sources including head motion, respiratory motion, and cardiac motion. The approaches for these techniques have commonly come in the form of hardware-driven gating and data-driven gating, where the distinguishing aspect is the use of external hardware to make motion measurements vs. deriving these measures from the data itself. The implementation of these techniques helps correct for motion artifacts and improves tracer uptake measurements. With the great impact that these methods have on the diagnostic and quantitative quality of PET images, much research has been performed in this area, and this paper outlines the various approaches that have been developed as applied to whole-body PET imaging.

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Mutations of isocitrate dehydrogenase 1 (IDH1) are key biomarkers for glioma classification, but current methods for detection of mutated IDH1 (mIDH1) require invasive tissue sampling and cannot be used for longitudinal studies. Positron emission tomography (PET) imaging with mIDH1-selective radioligands is a promising alternative approach that could enable non-invasive assessment of the IDH status. In the present work, we developed efficient protocols for the preparation of four 18F-labeled derivatives of the mIDH1-selective inhibitor olutasidenib. All four probes were characterized by cellular uptake studies with U87 glioma cells harboring a heterozygous IDH1 mutation (U87-mIDH) and the corresponding wildtype cells (U87-WT). In addition, the most promising probe was evaluated by PET imaging in healthy mice and mice bearing subcutaneous U87-mIDH and U87-WT tumors. Although all four probes inhibited mIDH1 with variable potencies, only one of them ([18F]mIDH-138) showed significantly higher in vitro uptake into U87-mIDH compared to U87-WT cells. In addition, PET imaging with [18F]mIDH-138 in mice demonstrated good in vivo stability and low non-specific uptake of the probe, but also revealed significantly higher uptake into U87-WT compared to U87-mIDH tumors. Finally, application of a two-tissue compartment model (2TCM) to the PET data indicated that preferential tracer uptake into U87-WT tumors results from higher specific binding rather than from differences in tracer perfusion. In conclusion, these results corroborate recent findings that mIDH1-selective inhibition may not directly correlate with mIDH1-selective target engagement and indicate that in vivo engagement of wildtype and mutated IDH1 may be governed by factors that are not faithfully reproduced by in vitro assays, both of which could complicate development of PET probes.

Asunto(s)

Radioisótopos de Flúor , Glioma , Isocitrato Deshidrogenasa , Mutación , Tomografía de Emisión de Positrones , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/antagonistas & inhibidores , Isocitrato Deshidrogenasa/metabolismo , Animales , Ratones , Radioisótopos de Flúor/química , Tomografía de Emisión de Positrones/métodos , Humanos , Línea Celular Tumoral , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/metabolismo , Glioma/patología , Radiofármacos/química

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PURPOSE: [18F]SynVesT-1 is a novel radiopharmaceutical for assessing synaptic density in vivo. This study aims to investigate the potential of [18F]SynVesT-1 positron emission tomography (PET) in evaluating neurological recovery in the rat model of ischemic stroke, and to compare its performance with [18F]FDG PET. METHODS: Sprague-Dawley rats were subjected to photothrombotic cerebral infarction, and safinamide was administered intraperitoneally from day 3 to day 14 post-stroke to alleviate neurological deficits. Cylinder test and forelimb placing test were performed to assess the neurological function. MRI, [18F]SynVesT-1 PET/CT and [18F]FDG PET/CT imaging were used to evaluate infarct volume, synaptic density, and cerebral glucose metabolism pre- and post-treatment. [18F]SynVesT-1 and [18F]FDG PET images were compared using Statistical Parametric Mapping (SPM) and region of interest (ROI)-based analysis. Post-mortem histological analysis was performed to validate PET images. RESULTS: Safinamide treatment improved behavioral outcomes in stroke-damaged rats. Both [18F]SynVesT-1 and [18F]FDG PET detected stroke-induced injury, with the injured region being significantly larger in [18F]FDG PET than in [18F]SynVesT-1 PET. Compared with the saline group, radiotracer uptake in the injured area significantly increased in [18F]SynVesT-1 PET after safinamide treatment, whereas no notable change was observed in [18F]FDG PET. Additionally, [18F]SynVesT-1 PET imaging showed a better correlation with neurological function recovery than [18F]FDG PET. Post-mortem analysis revealed increased neuronal numbers, synaptic density, and synaptic neuroplasticity, as well as decreased glia activation in the stroke-injured area after treatment. CONCLUSION: [18F]SynVesT-1 PET effectively quantified spatiotemporal dynamics of synaptic density in the rat model of stroke, and showed different capabilities in detecting stroke injury and neurological recovery compared with [18F]FDG PET. The utilization of [18F]SynVesT-1 PET holds promise as a potential non-invasive biomarker for evaluating ischemic stroke in conjunction with [18F]FDG PET.

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BACKGROUND: Brain serotonin 4 receptor (5-HT4R) levels are lower in untreated patients with Major Depressive Disorder (MDD) and are linked to verbal memory. We here investigate the relationship between 5-HT4R, clinical outcomes, and cognitive function in patients with MDD who initiate SSRI drug treatment. METHODS: Ninety moderately to severely depressed patients underwent molecular brain imaging to measure 5-HT4R binding prior to antidepressant treatment with escitalopram. Pretreatment 5-HT4R binding was assessed for its ability to predict treatment outcome at week 4, 8 or 12. In 40 patients rescanned 8 weeks post treatment, the change in cerebral 5-HT4R binding was correlated to change in verbal memory and to change in depressive symptoms, as evaluated by the Hamilton Depressive Rating Scale 6 (HAMD6). RESULTS: After 8 weeks of serotonergic intervention neostriatal 5-HT4R binding was reduced by 9%. Global change in 5-HT4R binding from baseline was associated with verbal memory outcomes, but not with overall clinical depressive symptom outcomes. Pretreatment 5-HT4R binding did not predict clinical recovery status at week 8, nor was it associated with change in HAMD6. CONCLUSIONS: In patients with moderate to severe MDD, treatment with SSRI's downregulates neostriatal 5-HT4R levels, consistent with the notion that the drugs increase cerebral extracellular serotonin. The less global brain 5-HT4R levels are downregulated after SSRIs, the more verbal memory improves, highlighting the potential importance of 5-HT4R as a treatment target in MDD. The findings offer insights to mechanisms underlying antidepressant effects and point to new directions for precision medicine treatments for MDD.

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OBJECTIVE: Positron Emission Tomography (PET) is a well-known imaging technology for the diagnosis, treatment, and monitoring of several diseases. Most PET scanners use a Ring-Shaped Detector Configuration (RSDC), which helps obtain homogeneous image quality but are restricted to an invariable Field-of-View (FOV), scarce spatial resolution, and low sensitivity. Alternatively, few PET systems use Open Detector Configurations (ODC) to permit an accessible FOV adaptable to different target sizes, thus optimizing sensitivity. Yet, to compensate the lack of angular coverage in ODC-PET, developing a detector with high-timing performance is mandatory to enable Time-of-Flight (TOF) techniques during reconstruction. The main goal of this work is to provide a proof of concept PET scanner appropriate for constructing the new generation of ODC-PET suitable for biopsy guidance and clinical intervention during acquisition. The designed detector has to be compact and robust, and its requirements in terms of performance are spatial and time resolutions < 2 mm and < 200 ps, respectively. METHODS: The present work includes a simulation study of an ODC-PET based on 2-panels with variable distance. The image quality (IQ) and Derenzo phantoms have been simulated and evaluated. The phantom simulations have also been performed using a ring-shaped PET for comparison purposes of the ODC approach with conventional systems. Then, an experimental evaluation of a prototype detector that has been designed following the simulation results is presented. This study focused on tuning the ASIC parameters and evaluating the scintillator surface treatment (ESR and TiO2), and configuration that yields the best Coincidence Time Resolution (CTR). Moreover, the scalability of the prototype to a module of 64 × 64mm2 and its preliminary evaluation regarding pixel identification are provided. RESULTS: The simulation results reported sensitivity (%) values at the center of the FOV of 1.96, 1.63, and 1.18 for panel distances of 200, 250, and 300 mm, respectively. The IQ reconstructed image reported good uniformity (87%) and optimal CRC values, and the Derenzo phantom reconstruction suggests a system resolution of 1.6-2 mm. The experimental results demonstrate that using TiO2 coating yielded better detector performance than ESR. Acquired data was filtered by applying an energy window of ± 30% at the photopeak level. After filtering, best CTR of 230 ± 2 ps was achieved for an 8 × 8 LYSO pixel block with 2 × 2 × 12mm3 each. The detector performance remained constant after scaling-up the prototype to a module of 64 × 64mm2, and the flood map demonstrates the module's capabilities to distinguish the small pixels; thus, a spatial resolution < 2 mm (pixel size) is achieved. CONCLUSIONS: The simulated results of this biplanar scanner show high performance in terms of image quality and sensitivity. These results are comparable to state-of-the-art PET technology and, demonstrate that including TOF information minimizes the image artifacts due to the lack of angular projections. The experimental results concluded that using TiO2 coating provide the best performance. The results suggest that this scanner may be suitable for organ study, breast, prostate, or cardiac applications, with good uniformity and CRC.

RESUMEN

BACKGROUND: Trop-2 is closely related to the development and progression of a variety of tumours and poor prognosis. This study aimed to construct an iodine-124 (124I)-labelled antibody-drug conjugate (ADC) positron emission tomography (PET) probe which could noninvasively image Trop-2 in vivo, providing an important method for the diagnosis of tumours with high Trop-2 expression in clinical practice and monitoring their treatment. METHODS: In this study, a novel Trop-2-targeting molecular probe, 124I-IMMU-132, was constructed to better reveal the expression of Trop-2. The targeting and binding abilities of the probe to Trop-2-positive tumours were investigated in Capan-1/MDA-MB-468/Mcf-7 cells and their animal models. RESULTS: The constructed 124I-IMMU-132 probe maintained both reliable radiochemical characteristics and binding affinity (Kd = 2.200 nmol/L). The uptake of the probe by Trop-2-positive Capan-1/MDA-MB-468 cells increased in a time-dependent manner. The probe bound specifically to Capan-1/MDA-MB-468 tumours in vivo. The SUVmax Tumour/muscle ratio gradually increased with time, from 4.30 ± 0.55-10.78 ± 1.80 (p < 0.01) in the Capan-1 model and from 8.84 ± 0.95-32.20 ± 2.9 (p < 0.001) in the MDA-MB-468 model. The biodistribution and pharmacokinetics of 124I-IMMU-132 in a mouse model were consistent with the imaging results, and the dosimetry estimation in humans was acceptable. CONCLUSIONS: 124I-IMMU-132 PET is a promising imaging technique for delineating Trop-2-positive tumours. It has great potential in early diagnosis and targeted selection of patients that could benefit from its application.

Asunto(s)

Antígenos de Neoplasias , Moléculas de Adhesión Celular , Inmunoconjugados , Radioisótopos de Yodo , Sondas Moleculares , Tomografía de Emisión de Positrones , Animales , Humanos , Antígenos de Neoplasias/metabolismo , Moléculas de Adhesión Celular/metabolismo , Tomografía de Emisión de Positrones/métodos , Línea Celular Tumoral , Sondas Moleculares/farmacocinética , Sondas Moleculares/química , Distribución Tisular , Ratones , Inmunoconjugados/farmacocinética , Ratones Desnudos , Femenino , Ratones Endogámicos BALB C , Radiofármacos/farmacocinética , Células MCF-7

RESUMEN

Colorectal cancer (CRC) is among the most lethal and prevalent malignancies in the world. Human epidermal growth factor receptor 2 (HER2) is a promising target for the diagnosis and treatment of CRC. In this study, we aimed to design, synthesize and label peptide-based positron emission tomography (PET) tracers targeting HER2-positive CRC, namely [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02. The results show that [68Ga]Ga-ES-01 and [68Ga]Ga-ES-02 possessed hydrophilicity, rapid pharmacokinetic properties and excellent stabilities. [68Ga]Ga-ES-02 demonstrated higher binding affinity (Kd = 24.29 ± 4.95 nM) toward the HER2 in CRC. In HER2-positive HT-29 CRC xenograft mouse model, PET study showed specific tumor uptake after injection of [68Ga]Ga-ES-02 (SUV15min max = 0.87 ± 0.03; SUV30min max = 0.64 ± 0.02). In biodistribution study, the T/M ratios of 68Ga-ES-02 at 30 min after injection reached a maximum of 4.07 ± 0.34. In summary, we successfully synthesized and evaluated two novel peptide-based PET tracers. Our data demonstrate that [68Ga]Ga-ES-01/02 is capable of HER2-positive colorectal cancer, with [68Ga]Ga-ES-02 showing superior imaging effect, enhanced targeting, and increased specificity.

Asunto(s)

Neoplasias Colorrectales , Radioisótopos de Galio , Péptidos , Tomografía de Emisión de Positrones , Receptor ErbB-2 , Humanos , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Radioisótopos de Galio/química , Animales , Receptor ErbB-2/metabolismo , Ratones , Péptidos/química , Péptidos/síntesis química , Distribución Tisular , Estructura Molecular , Radiofármacos/química , Radiofármacos/síntesis química , Radiofármacos/farmacología , Radiofármacos/farmacocinética , Ratones Desnudos , Proliferación Celular/efectos de los fármacos , Células HT29 , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/tratamiento farmacológico , Ratones Endogámicos BALB C , Femenino

RESUMEN

BACKGROUND: Residual image noise is substantial in positron emission tomography (PET) and one of the factors limiting lesion detection, quantification, and overall image quality. Thus, improving noise reduction remains of considerable interest. This is especially true for respiratory-gated PET investigations. The only broadly used approach for noise reduction in PET imaging has been the application of low-pass filters, usually Gaussians, which however leads to loss of spatial resolution and increased partial volume effects affecting detectability of small lesions and quantitative data evaluation. The bilateral filter (BF) - a locally adaptive image filter - allows to reduce image noise while preserving well defined object edges but manual optimization of the filter parameters for a given PET scan can be tedious and time-consuming, hampering its clinical use. In this work we have investigated to what extent a suitable deep learning based approach can resolve this issue by training a suitable network with the target of reproducing the results of manually adjusted case-specific bilateral filtering. METHODS: Altogether, 69 respiratory-gated clinical PET/CT scans with three different tracers ( [ 18 F ] FDG, [ 18 F ] L-DOPA, [ 68 Ga ] DOTATATE) were used for the present investigation. Prior to data processing, the gated data sets were split, resulting in a total of 552 single-gate image volumes. For each of these image volumes, four 3D ROIs were delineated: one ROI for image noise assessment and three ROIs for focal uptake (e.g. tumor lesions) measurements at different target/background contrast levels. An automated procedure was used to perform a brute force search of the two-dimensional BF parameter space for each data set to identify the "optimal" filter parameters to generate user-approved ground truth input data consisting of pairs of original and optimally BF filtered images. For reproducing the optimal BF filtering, we employed a modified 3D U-Net CNN incorporating residual learning principle. The network training and evaluation was performed using a 5-fold cross-validation scheme. The influence of filtering on lesion SUV quantification and image noise level was assessed by calculating absolute and fractional differences between the CNN, manual BF, or original (STD) data sets in the previously defined ROIs. RESULTS: The automated procedure used for filter parameter determination chose adequate filter parameters for the majority of the data sets with only 19 patient data sets requiring manual tuning. Evaluation of the focal uptake ROIs revealed that CNN as well as BF based filtering essentially maintain the focal SUV max values of the unfiltered images with a low mean ± SD difference of δ SUV max CNN , STD = (-3.9 ± 5.2)% and δ SUV max BF , STD = (-4.4 ± 5.3)%. Regarding relative performance of CNN versus BF, both methods lead to very similar SUV max values in the vast majority of cases with an overall average difference of δ SUV max CNN , BF = (0.5 ± 4.8)%. Evaluation of the noise properties showed that CNN filtering mostly satisfactorily reproduces the noise level and characteristics of BF with δ Noise CNN , BF = (5.6 ± 10.5)%. No significant tracer dependent differences between CNN and BF were observed. CONCLUSIONS: Our results show that a neural network based denoising can reproduce the results of a case by case optimized BF in a fully automated way. Apart from rare cases it led to images of practically identical quality regarding noise level, edge preservation, and signal recovery. We believe such a network might proof especially useful in the context of improved motion correction of respiratory-gated PET studies but could also help to establish BF-equivalent edge-preserving CNN filtering in clinical PET since it obviates time consuming manual BF parameter tuning.