Immunorecognition provides an excellent basis for targeted imaging techniques covering a wide range from basic research to diagnostics and from single cells to whole organisms. Fluorescence- or radioisotope-labeled antibodies, antibody fragments or nanobodies enable a direct signal readout upon binding and allow for versatile imaging from microscopy to whole-body imaging. However, as the signal intensity directly correlates with the number of labeled antibodies bound to their epitopes (1:1 binding), sensitivity for low-expressing epitopes can be limiting for visualization. For the first time, we developed poly-epitope tags with multiple copies (1 to 7) of a short peptide epitope, specifically the MoonTag, that are recognized by a labeled nanobody and aimed at signal amplification in microscopy and cell-specific PET imaging. In transiently transfected HeLa cells or stably transduced A4573 cells we characterized complex formation and in vitro signal amplification. Indeed, using fluorescently and radioactively labeled nanobodies we found an approximately linear signal amplification with increasing numbers of epitope copies in vitro. To test the poly-epitope approach in vivo, A4573 tumor cells were injected subcutaneously into the shoulder of NSG mice, with A4573 tumor cells expressing a poly-epitope of 7 MoonTags on one side and WT cells on the other side. Using a [68Ga]-labeled NODAGA-conjugated MoonTag nanobody, we performed PET/CT imaging at day 8-9 after tumor implantation. Specific binding of a [68Ga]-labeled NODAGA-conjugated MoonTag nanobody was observed in 7xMoonTag tumors (1.7 ± 0.5%ID/mL) by PET imaging, showing significantly higher radiotracer accumulation compared to the WT tumors (1.1 ± 0.3%ID/mL; p < 0.01). Ex vivo gamma counter measurements confirmed significantly higher uptake in 7xMoonTag tumors compared to WT tumors (p < 0.001). In addition, MoonTag nanobody binding was detected by autoradiography which was spatially matched with histological analysis of the tumor tissues. In conclusion, we expect nanobody-based poly-epitope tag strategies to be widely applicable for multimodal imaging techniques given the advantageous properties of nanobodies and their amenability to genetic and chemical engineering.

BACKGROUND: Amyloid positron emission tomography (PET) acquisition timing impacts quantification.
METHODS: In florbetaben (FBB) PET scans of 245 adults with and without cognitive impairment, we investigated the impact of post-injection acquisition time on Centiloids (CLs) across five reference regions. CL equations for FBB were derived using standard methods, using FBB data collected between 90 and 110 min with paired Pittsburgh compound B data. Linear mixed models and t-tests evaluated the impact of acquisition time on CL increases.
RESULTS: CL values increased significantly over the scan using the whole cerebellum, cerebellar gray matter, and brainstem as reference regions, particularly in amyloid-positive individuals. In contrast, CLs based on white matter-containing reference regions decreased across the scan.
CONCLUSIONS: The quantification of CLs in FBB PET imaging is influenced by both the overall scan acquisition time and the choice of reference region. Standardized acquisition protocols or the application of acquisition time-specific CL equations should be implemented in clinical protocols.
CONCLUSIONS: Acquisition timing affects florbetaben positron emission tomography (PET) scan quantification, especially in amyloid-positive participants. The impact of acquisition timing on quantification varies across common reference regions. Consistent acquisitions and/or appropriate post-injection adjustments are needed to ensure comparability of PET data.

UNASSIGNED: Epithelioid hemangioma (EH) is an intermediate locally aggressive tumor that consists of epithelioid cells and endothelial cell differentiation, which can occur at any age, but is most common between the ages of 30 and 40 years. EH in the thoracic spine is rare, and accurate diagnosis is critical to treatment planning. Our aim was to explore the imaging and clinical data of thoracic spine EH to improve the understanding of this rare disease.
UNASSIGNED: From January 1, 2018 to June 30, 2023, a database of thoracic spine masses was retrospectively reviewed. Five patients with histologically proven thoracic spine EH and complete imaging available were identified and analyzed. Computed tomography (CT) and magnetic resonance imaging (MRI) findings were evaluated separately by two radiologists with more than 10 years of experience. Positron emission tomography (PET)/CT was conducted by two nuclear medicine diagnostic technologists with at least 5 years of experience.
UNASSIGNED: The patients included three male and two female patients aged 23 to 56 years (mean age was 38.4 ± 14.3 years). All patients underwent CT, MRI, and 18F-FDG PET/CT examination before treatment. Four patients were limited to one vertebral involvement, only one patient had multiple vertebral involvement, and all tumors involved the accessories, including one involving the posterior ribs. The maximum diameter of the tumor ranged from 2.7 to 4.3.
UNASSIGNED: CT, MRI, and 18F-FDG PET/CT findings of thoracic spine EH have certain characteristics, and understanding these imaging findings will help to obtain accurate diagnosis before surgery.

Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [68Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [68Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.

Nowadays, the utility of positron emission tomography/computed tomography (PET/CT) is well established in nasopharyngeal carcinoma (NPC). The incidence of NPC in the West population, especially in children, is very low. We present the first Italian case of a pediatric patient with NPC followed up with 18F-fluorodeoxyglucose (18F-FDG) PET/CT scan in addition to the standard follow-up imaging methods, including CT and magnetic resonance imaging. The 18F-FDG PET/CT scan was helpful in discriminating between metastatic and benign osseous lesions, thereby helping clinicians to determine the most appropriate therapeutic regimen. These findings support the clinical utility of 18F-FDG PET/CT in the diagnostic work-up of pediatric patients with NPC.
Günümüzde nazofaringeal karsinomda (NFK) pozitron emisyon tomografisi/bilgisayarlı tomografinin (PET/BT) kullanımı iyice yerleşmiştir. Batı popülasyonunda, özellikle de pediatrik yaşta NFK’nin görülme sıklığı çok düşüktür. BT ve manyetik rezonans görüntüleme dahil olmak üzere standart takip görüntüleme yöntemlerine ek olarak 18F-florodeoksiglukoz (18F-FDG) PET/BT taraması yoluyla takip edilen NFK’li ilk İtalyan pediatrik hastayı sunuyoruz. 18F-FDG PET/BT taraması, metastatik ve iyi huylu kemik lezyonları arasında ayrım yapılmasında ve klinisyenlerin en uygun terapötik rejimi belirlemesine yardımcı olmuştur. Bu bulgular, NFK’li pediatrik hastaların tanısal çalışmalarında 18F-FDG PET/BT taramasının klinik faydasını desteklemektedir.

UNASSIGNED: Obesity impairs bone marrow (BM) glucose metabolism. Adult BM constitutes mostly of adipocytes that respond to changes in energy metabolism by modulating their morphology and number. Here we evaluated whether diet or exercise intervention could improve the high-fat diet (HFD) associated impairment in BM glucose uptake (BMGU) and whether this associates with the morphology of BM adipocytes (BMAds) in rats.
UNASSIGNED: Eight-week-old male Sprague-Dawley rats were fed ad libitum either HFD or chow diet for 24 weeks. Additionally after 12 weeks, HFD-fed rats switched either to chow diet, voluntary intermittent running exercise, or both for another 12 weeks. BMAd morphology was assessed by perilipin-1 immunofluorescence staining in formalin-fixed paraffin-embedded tibial sections. Insulin-stimulated sternal and humeral BMGU were measured using [18F]FDG-PET/CT. Tibial microarchitecture and mineral density were measured with microCT.
UNASSIGNED: HFD rats had significantly higher whole-body fat percentage compared to the chow group (17% vs 13%, respectively; p = 0.004) and larger median size of BMAds in the proximal tibia (815 µm2 vs 592 µm2, respectively; p = 0.03) but not in the distal tibia. Switch to chow diet combined with running exercise normalized whole-body fat percentage (p < 0.001) but not the BMAd size. At 32 weeks of age, there was no significant difference in insulin-stimulated BMGU between the study groups. However, BMGU was significantly higher in sternum compared to humerus (p < 0.001) and higher in 8-week-old compared to 32-week-old rats (p < 0.001). BMAd size in proximal tibia correlated positively with whole-body fat percentage (r = 0.48, p = 0.005) and negatively with humeral BMGU (r = -0.63, p = 0.02). HFD significantly reduced trabecular number (p < 0.001) compared to the chow group. Switch to chow diet reversed this as the trabecular number was significantly higher (p = 0.008) than in the HFD group.
UNASSIGNED: In this study we showed that insulin-stimulated BMGU is age- and site-dependent. BMGU was not affected by the study interventions. HFD increased whole-body fat percentage and the size of BMAds in proximal tibia. Switching from HFD to a chow diet and running exercise improved glucose homeostasis and normalized the HFD-induced increase in body fat but not the hypertrophy of BMAds.

Among the diverse populations of myeloid cells that reside within the healthy and diseased heart, C-C chemokine receptor 2 (CCR2) is specifically expressed on inflammatory populations of monocytes and macrophages that contribute to the development and progression of heart failure1-4. Here, we evaluated a peptide-based imaging probe (64Cu-DOTA-ECL1i) that specifically recognizes CCR2+ monocytes and macrophages for human cardiac imaging. Compared to healthy controls, 64Cu-DOTA-ECL1i heart uptake was increased in subjects following acute myocardial infarction, predominately localized within the infarct area, and was associated with impaired myocardial wall motion. These findings establish the feasibility of molecular imaging of CCR2 expression to visualize inflammatory monocytes and macrophages in the injured human heart.

UNASSIGNED: Creutzfeldt-Jakob disease is a neurodegenerative disorder caused by brain accumulation of a misfolded form of the cellular prion protein, whose diagnosis is challenging, particularly in early stages, due to the variability and nonspecificity of the clinical and radiological features. 18F-fluorodeoxyglucose positron-emitted tomography has the potential to be considered a crucial investigation in these patients, revealing metabolic abnormalities earlier than the conventional neuroimaging analysis.
UNASSIGNED: A 59-year-old man, the military officer, was referred to our Units for the onset of neurological symptoms rapidly evolving within a month, characterized by akinetic mutism, constructional apraxia, and disorders of spatial orientation. Brain 18F-fluorodeoxyglucose (18F-FDG) positron-emitted tomography (PET)/CT depicted an asymmetric hypometabolism in the left fronto-temporo-parietal cortex, as well as in the left thalamus and the right cerebellar hemisphere, while the glucose metabolism appears to be preserved in the somatosensory cortex and the basal ganglia. Laboratory routine analyses, cerebrospinal fluid routine, infective tests, electroencephalography (EEG), and brain magnetic resonance (MR) were all unremarkable. A positive RT-QuIC result on cerebro-spinal fluid (CSF) was subsequently shown, without any pathogenic gene mutations and, therefore, the result was consistent with a diagnosis of sporadic Creutzfeld-Jacob disease. The clinical evolution was quickly unfavorable, and the patient died about 4 months after hospital admission. FDG PET/computed tomography (CT) has the potential to be considered a crucial investigation in these patients, documenting metabolic changes long time before other diagnostic investigations such as CSF, EEG, brain CT, and brain MR, thus suggesting a greater sensitivity of glucose metabolic evaluation in the early stage of the disease in question.

Absence seizures are classically associated with behavioral arrest and transient deficits in consciousness, yet substantial variability exists in the severity of the impairment. Despite several decades of research on the topic, the pathophysiology of absence seizures and the mechanisms underlying behavioral impairment remain unclear. Several rationales have been proposed including widespread cortical deactivation, reduced perception of external stimuli, and transient suspension of the default mode network, among others. This review aims to summarize the current knowledge on the neural correlates of impaired consciousness in absence seizures. We review evidence from studies using animal models of absence epilepsy, electroencephalography, functional magnetic resonance imaging, magnetoencephalography, positron emission tomography, and single photon emission computed tomography.

As silicon photomultiplier (SiPM)-based time-of-flight (TOF) positron emission tomography (PET) becomes popular, the need for sophisticated PET data acquisition (DAQ) systems is increasing. One promising solution to this challenge is the adoption of a field-programmable gate array (FPGA)-only signal digitization method. In this paper, we propose a new approach to efficiently implement an FPGA-only digitizer. We configured the input/output (IO) port of the FPGA to function as a dual-threshold voltage comparator through the use of simple passive circuitry and heterogeneous IO standards. This configuration overcomes the limitations of existing methods by allowing different threshold voltages for adjacent IO pins, effectively reducing routing complexity and lowering manufacturing costs. An FPGA-only digitizer was implemented by integrating the dual-threshold voltage comparator and FPGA-based time-to-digital converter. By combining the dual-threshold time-over-threshold (TOT) method and curve fitting, precise energy information could be obtained. The performance of the FPGA-only digitizer was assessed using a detector setup comprising a 3 × 3 × 20 mm3 LYSO scintillation crystal and a single pixel SiPM. Using the configured evaluation setup, an energy resolution of 12.5% and a time resolution of 146 ± 9 ps were achieved for a 20 mm scintillation crystal. The dual-threshold TOT implemented using the proposed method showed consistent linearity across an energy range of 100 keV to 600 keV. The proposed method is well-suited for the development of cost-effective DAQ systems in highly integrated TOF PET systems.