Evaluation of the Therapeutical Effect of Matricaria Chamomilla Extract vs. Galantamine on Animal Model Memory and Behavior Using 18F-FDG PET/MRI.

The memory-enhancing activity of Matricaria chamomilla hydroalcoholic extract (MCE) is already being investigated by behavioral and biochemical assays in scopolamine-induced amnesia rat models, while the effects of scopolamine (Sco) on cerebral glucose metabolism are examined as well. Nevertheless, the study of the metabolic profile determined by an enriched MCE has not been performed before. The present experiments compared metabolic quantification in characteristic cerebral regions and behavioral characteristics for normal, only diseased, diseased, and MCE- vs. Galantamine (Gal)-treated Wistar rats. A memory deficit was induced by four weeks of daily intraperitoneal Sco injection. Starting on the eighth day, the treatment was intraperitoneally administered 30 min after Sco injection for a period of three weeks. The memory assessment comprised three maze tests. Glucose metabolism was quantified after the 18F-FDG PET examination. The right amygdala, piriform, and entorhinal cortex showed the highest differential radiopharmaceutical uptake of the 50 regions analyzed. Rats treated with MCE show metabolic similarity with normal rats, while the Gal-treated group shows features closer to the diseased group. Behavioral assessments evidenced a less anxious status and a better locomotor activity manifested by the MCE-treated group compared to the Gal-treated group. These findings prove evident metabolic ameliorative qualities of MCE over Gal classic treatment, suggesting that the extract could be a potent neuropharmacological agent against amnesia.

Radiolabeled multi-layered coated gold nanoparticles as potential biocompatible PET/SPECT tracers.

The demand for tailored, disease-adapted, and easily accessible radiopharmaceuticals is one of the most persistent challenges in nuclear imaging precision medicine. The aim of this work was to develop two multimodal radiotracers applicable for both SPECT and PET techniques, which consist of a gold nanoparticle core, a shell involved in radioisotope entrapment, peripherally placed targeting molecules, and biocompatibilizing polymeric sequences. Shell decoration with glucosamine units located in sterically hindered molecular environments is expected to result in nanoparticle accumulation in high-glucose-consuming areas. Gold cores were synthesized using the Turkevich method, followed by citrate substitution with linear PEG α,ω-functionalized with thiol and amine groups. The free amine groups facilitated the binding of branched polyethyleneimine through an epoxy ring-opening reaction by using PEG α,ω-diglycidyl ether as a linker. Afterwards, the glucose-PEG-epoxy prepolymer has been grafted onto the surface of AuPEG-PEI conjugates. Finally, the AuPEG-PEI-GA conjugates were radiolabeled with 99mTc or 68Ga. Instant thin-layer chromatography was used to evaluate the radiolabeling yield. The biocompatibility of non-labeled and 99mTc or 68Ga labeled nanoparticles was assessed on normal fibroblasts. The 99mTc complexes remained stable for over 22 hours, while the 68Ga containing ones revealed a slight decrease in stability after 1 hour.

Are MTV and TLG Accurate for Quantifying the Intensity of Brown Adipose Tissue Activation?

Recent research has suggested that one novel mechanism of action for anti-obesity medications is to stimulate the activation of brown adipose tissue (BAT). 18FDG PET/CT remains the gold standard for defining and quantifying BAT. SUVmax is the most often used quantification tool in clinical practice. However, this parameter does not reflect the entire BAT volume. As a potential method for precisely evaluating BAT, we have utilised metabolic tumour volume (MTV) and total lesion glycolysis (TLG) to answer the question: Are MTV and TLG accurate in quantifying the intensity of BAT activation? After analysing the total number of oncological 18F-FDG PET/CT scans between 2021-2023, we selected patients with active BAT. Based on the BAT SUVmax, the patients were divided into BAT-moderate activation (MA) vs. BAT-high activation (HA). Furthermore, we statistically analysed the accuracy of TLG and MTV in assessing BAT activation intensity. The results showed that both parameters increased their predictive value regarding BAT activation, and presented a significantly high sensitivity and specificity for the correct classification of BAT activation intensity. To conclude, these parameters could be important indicators with increased accuracy for classifying BAT expression, and could bring additional information about the volume of BAT to complement the limitations of the SUVmax.

Targeted Alpha Therapy: All We Need to Know about 225Ac's Physical Characteristics and Production as a Potential Theranostic Radionuclide.

The high energy of α emitters, and the strong linear energy transfer that goes along with it, lead to very efficient cell killing through DNA damage. Moreover, the degree of oxygenation and the cell cycle state have no impact on these effects. Therefore, α radioisotopes can offer a treatment choice to individuals who are not responding to ß- or gamma-radiation therapy or chemotherapy drugs. Only a few α-particle emitters are suitable for targeted alpha therapy (TAT) and clinical applications. The majority of available clinical research involves 225Ac and its daughter nuclide 213Bi. Additionally, the 225Ac disintegration cascade generates γ decays that can be used in single-photon emission computed tomography (SPECT) imaging, expanding the potential theranostic applications in nuclear medicine. Despite the growing interest in applying 225Ac, the restricted global accessibility of this radioisotope makes it difficult to conduct extensive clinical trials for many radiopharmaceutical candidates. To boost the availability of 225Ac, along with its clinical and potential theranostic applications, this review attempts to highlight the fundamental physical properties of this α-particle-emitting isotope, as well as its existing and possible production methods.

Off the Beaten Path in Oncology: Active Brown Adipose Tissue by Virtue of Molecular Imaging.

Brown Adipose Tissue (BAT) is considered beneficial in diabetes and obesity, but it can also have negative effects such as its implication in tumours' pathogenesis and the development of Cancer-induced Cachexia. Since 18F-FDG PET/CT is a common molecular imaging modality used in cancer assessment, we aim to study the 18F-FDG BAT biodistribution in oncological patients and look for possible correlations between BAT activity and different malignancies as well as the patient's weight status. After analysing the total number of oncological 18F-FDG PET/CT scans between 2017 and 2021, we selected patients with active BAT. Based on their BMI, the selected patients were divided into nonobese (NO) vs. overweight and obese (OOB). OOB SUVmaxlean body mass(LBM) had the highest mean values in supraclavicular, latero-cervical, and paravertebral vs. mediastinal and latero-thoracic localisations in NO. BMI was positively correlated with latero-cervical and supraclavicular SUVmax(LBM) but negatively correlated with latero-thoracic and abdominal SUVmax(LBM). Considering the age of the patients, SUVmax(LBM) decreases in the latero-cervical, paravertebral, and abdominal regions. In addition, the males presented lower SUVmax(LBM) values. SUVmax(LBM) was not affected by the treatment strategy or the oncological diagnosis. To conclude, it is mandatory to take into consideration the BAT particularities and effects on weight status in order to optimise the clinical management of oncological patients.

Brown Adipose Tissue Biodistribution and Correlations Particularities in Parathyroid Pathology Personalized Diagnosis.

Brown adipose tissue (BAT) participates in the regulation of whole-body metabolism by producing a variety of adipokines. This study investigates into the BAT pattern and the clinical aspects of overweight and obese (OOB) vs. non-obese (NO) hyperparathyroidism (HPT) patients with the aim of assessing the impact of BAT and obesity on HPT. Parathyroid scans performed on 441 HPT patients between 2015 and 2020 were retrospectively analyzed in order to select the images with active BAT. Based on their BMI, the patients with active BAT were divided into OOB vs. NO. The results showed that BAT was present in cervical and supraclavicular regions, with a single localization especially among NO vs. multiple sites among OOB. The (total counts/pixels)BAT/(total counts/pixels)non-BAT ratio in the right cervical localization showed a significant difference between the groups with higher values in OOB. BMI, PTH, FT4, vitamin D, magnesium, creatinine, and urea had significant correlations with BAT ratios. The predictive values showed that right cervical ratios higher than 1.52 and right supraclavicular ratios lower than 1.15 indicated an increased probability of being OOB. The significant correlations between BAT activation in OOB vs. NO and HPT clinical parameters could be useful for developing potential treatments based on this tissue.

Role of Diphosphonates Bone Scintigraphy in Correlation with Biomarkers for a Personalized Approach to ATTR Cardiac Amyloidosis in North-Eastern Romania.

Transthyretin cardiac amyloidosis (ATTR) is a rare cardiac protein deposition disease characterized by progressive thickening of both ventricles, the inter-atrial-ventricular septum and the atrioventricular valves. The gold standard method for diagnosing this rare pathology is endomyocardial biopsy. If this method cannot be used, the alternative is a mixture of clinical and paraclinical tests. Over the course of five years, we examined 58 patients suspected of cardiac amyloidosis based on electrocardiography and ultrasonography criteria, who had been sent for bone scintigraphy in order to determine the presence of ATTR cardiac amyloidosis. However, the final diagnosis was set by correlating the bone scan with genetic testing, free light chain dosage or soft tissue biopsy. Based on the final diagnosis we analyzed the patients' predominant biomarkers in order to determine a possible correlation between them. This analysis is designed to help the general practitioner set a possible cardiac amyloidosis diagnosis.

Improved Personalised Neuroendocrine Tumours' Diagnosis Predictive Power by New Receptor Somatostatin Image Processing Quantification.

Although neuroendocrine tumours (NETs) are intensively studied, their diagnosis and consequently personalised therapy management is still puzzling due to their tumoral heterogeneity. In their theragnosis algorithm, receptor somatostatin scintigraphy takes the central place, the diagnosis receptor somatostatin analogue (RSA) choice depending on laboratory experience and accessibility. However, in all cases, the results depend decisively on correct radiotracer tumoral uptake quantification, where unfortunately there are still unrevealed clues and lack of standardization. We propose an improved method to quantify the biodistribution of gamma-emitting RSA, using tissular corrected uptake indices. We conducted a bi-centric retrospective study on 101 patients with different types of NETs. Three uptake indices obtained after applying new corrections to areas of interest drawn for the tumour and for three reference organs (liver, spleen and lung) were statistically analysed. For the corrected pathological uptake indices, the results showed a significant decrease in the error of estimating the occurrence of errors and an increase in the diagnostic predictive power for NETs, especially in the case of lung-referring corrected index. In conclusion, these results support the importance of corrected uptake indices use in the analysis of 99mTcRSA biodistribution for a better personalised diagnostic accuracy of NETs patients.

Transthyretin cardiac amyloidosis: a review of the nuclear imaging findings with emphasis on the radiotracers mechanisms.

Cardiac amyloidosis is a protein deposition disease characterized by the infiltration of the myocardium and coronary arteries resulting in a progressive thickening of both ventricles, interatrial septum and atrioventricular valves, eventually leading to organ failure. It is a disease hard to diagnose, due to the lack of diagnostic investigations. However, development of new and more accurate examinations is undergoing. Endomyocardial biopsy is the gold standard investigation for this disease, but it has its limitations (invasive and not widely available). Other investigations may be able to detect the presence of cardiac amyloidosis but cannot specify the type involved. To that end, nuclear medicine through bone scanning offers a simple, non-invasive solution to detect, differentiate and diagnose transthyretin cardiac amyloidosis (ATTR) from other types of cardiac amyloidosis. In order to demonstrate the importance of bone scanning we will present a few methods of image processing based on literature and a personalized method, followed by a few important examples of positive cases. The aim of this review was to present the current methods of ATTR detection with emphasis on nuclear medicine bone scanning and its important place in the decision algorithm of the cardiologist for a personalized approach to this pathology.