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The residence time distribution (RTD) is very reliable, providing valuable information about the performance of process equipment such as reactors and columns. The aim of this work is to study the effect of agitation in the hydrodynamic column of flow-rig. In this case, residence time distribution (RTD) is determined using the radiotracer approach. The radiotracer is the Technetium Tc-99m with half decay 6 h. It also emits gamma rays with an energy of 0.140 MeV. 2 mL of approximately 9 mCi activity Tc-99m was injected inside the column. The results show that in the conditions studied the column presents the anomaly, dead volume. The Intensity function A(t) confirms this result. Agitation has a beneficial effect in the reduction of dead volume. To revise the conception of the column or study other parameters like the variation flow rate can reduce or eliminate the dead volume. The RTD model indicated the column behaved as a Plug flow reactor (PFR) with mixing cells in serie (J = 4) model and the RTD experiment verified the model well. [ABSTRACT FROM AUTHOR]

In order to contribute to the sufficient supply of clinical 99mTc(VII), the sorption behavior of neutron-produced 99Mo(VI) was investigated on synthetized single and binary Ti and Zr xerogels treated at different temperatures, under normal operating conditions. Materials were prepared by the sol–gel method and characterized by several techniques. Sorption batch systems were performed using 99Mo radiotracer to determine the metallic affinity as a function of pH, and a methodology was developed in order to obtain the maximum capacities by surface saturation, where the Ti-388, TiZr-388 (3:1) and Zr-388 samples showed the most noteworthy sorption behaviors (33.1 ± 0.34 mg/g at pH ∼ 6.0, 31.7 ± 0.27 mg/g at pH ∼ 6.5, and 23.5 ± 0.61 mg/g at pH ∼ 6.8, respectively). The molybdenum-99 sorption behavior was also studied by fitting to the Freundlich and Langmuir models, and all xerogels could be described as heterogeneous materials with favorable 99Mo sorption properties. Finally, preliminary studies of clinical-scale 99Mo/99mTc generators were performed, the results revealed the next maximum 99mTc elution yield order Ti-388 (89.6 %) > TiZr-388 (3:1) (86.7 %) > Zr-388 (77.7 %). [ABSTRACT FROM AUTHOR]

Here, we describe the characterization of a radioligand selective for GluN2B‐containing NMDA receptors, 3‐[3H] 1‐(azetidin‐1‐yl)‐2‐(6‐(4‐fluoro‐3‐methyl‐phenyl)pyrrolo[3,2‐b]pyridin‐1‐yl)ethanone ([3H]‐JNJ‐ GluN2B‐5). In rat cortical membranes, the compound bound to a single site, and the following kinetic parameters were measured; association rate constant Kon = 0.0066 ± 0.0006 min−1 nM−1, dissociation rate constant Koff = 0.0210 ± 0.0001 min−1 indicating calculated KD = Koff/Kon = 3.3 ± 0.4 nM, (mean ± SEM, n = 3). The equilibrium dissociation constant determined from saturation binding experiments in rat cortex was KD of 2.6 ± 0.3 nM (mean ± SEM, n = 3). In contrast to the widely used GluN2B radioligand [3H]‐Ro 25‐6981, whose affinity Ki for sigma 1 and sigma 2 receptors are 2 and 189 nM, respectively, [3H]‐JNJ‐GluN2B‐5 exhibits no measurable affinity for sigma 1 and sigma 2 receptors (Ki > 10 μM for both) providing distinct selectivity advantages. Anatomical distribution of [3H]‐JNJ‐GluN2B‐5 binding sites in rat, mouse, dog, monkey, and human brain tissue was studied using in vitro autoradiography, which showed high specific binding in the hippocampus and cortex and negligible binding in the cerebellum. Enhanced selectivity for GluN2B‐containing receptors translated to a good signal‐to‐noise ratio in both in vitro radioligand binding and in vitro autoradiography assays. In conclusion, [3H]‐JNJ‐GluN2B‐5 is a high‐affinity GluN2B radioligand with excellent signal‐to‐noise ratio and unprecedented selectivity. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) imaging studies in laboratory animals are almost always performed under isoflurane anesthesia to ensure that the subject stays still during the image acquisition. Isoflurane is effective, safe, and easy to use, and it is generally assumed to not have an impact on the imaging results. Motivated by marked differences observed in the brain uptake and metabolism of the PET tracer 3‐[18F]fluoro‐4‐aminopyridine [(18F]3F4AP) between human and nonhuman primate studies, this study investigates the possible effect of isoflurane on this process. Mice received [18F]3F4AP injection while awake or under anesthesia and the tracer brain uptake and metabolism was compared between groups. A separate group of mice received the known cytochrome P450 2E1 inhibitor disulfiram prior to tracer administration. Isoflurane was found to largely abolish tracer metabolism in mice (74.8 ± 1.6 vs. 17.7 ± 1.7% plasma parent fraction, % PF) resulting in a 4.0‐fold higher brain uptake in anesthetized mice at 35 min post‐radiotracer administration. Similar to anesthetized mice, animals that received disulfiram showed reduced metabolism (50.0 ± 6.9% PF) and a 2.2‐fold higher brain signal than control mice. The higher brain uptake and lower metabolism of [18F]3F4AP observed in anesthetized mice compared to awake mice are attributed to isoflurane's interference in the CYP2E1‐mediated breakdown of the tracer, which was confirmed by reproducing the effect upon treatment with the known CYP2E1 inhibitor disulfiram. These findings underscore the critical need to examine the effect of isoflurane in PET imaging studies before translating tracers to humans that will be scanned without anesthesia. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzymes (ACE) are well-known for their roles in both blood pressure regulation via the renin-angiotensin system as well as functions in fertility, immunity, hematopoiesis, and many others. The two main isoforms of ACE include ACE and ACE-2 (ACE2). Both isoforms have similar structures and mediate numerous effects on the cardiovascular system. Most remarkably, ACE2 serves as an entry receptor for SARS-CoV-2. Understanding the interaction between the virus and ACE2 is vital to combating the disease and preventing a similar pandemic in the future. Noninvasive imaging techniques such as positron emission tomography and single photon emission computed tomography could noninvasively and quantitatively assess in vivo ACE2 expression levels. ACE2-targeted imaging can be used as a valuable tool to better understand the mechanism of the infection process and the potential roles of ACE2 in homeostasis and related diseases. Together, this information can aid in the identification of potential therapeutic drugs for infectious diseases, cancer, and many ACE2-related diseases. The present review summarized the state-of-the-art radiotracers for ACE2 imaging, including their chemical design, pharmacological properties, radiochemistry, as well as preclinical and human molecular imaging findings. We also discussed the advantages and limitations of the currently developed ACE2-specific radiotracers. [ABSTRACT FROM AUTHOR]

Background: The cysteine-aspartic acid protease caspase-3 is recognized as the main executioner of apoptosis in cells responding to specific extrinsic and intrinsic stimuli. Caspase-3 represents an interesting biomarker to evaluate treatment response, as many cancer therapies exert their effect by inducing tumour cell death. Previously developed caspase-3 PET tracers were unable to reach routine clinical use due to low tumour uptake or lack of target selectivity, which are two important requirements for effective treatment response evaluation in cancer patients. Therefore, the goal of this study was to develop and preclinically evaluate novel caspase-3-selective activity-based probes (ABPs) for apoptosis imaging. Results: A library of caspase-3-selective ABPs was developed for tumour apoptosis detection. In a first attempt, the inhibitor Ac-DW3-KE (Ac-3Pal-Asp-βhLeu-Phe-Asp-KE) was 18F-labelled on the N-terminus to generate a radiotracer that was incapable of adequately detecting an increase in apoptosis in vivo. The inability to effectively detect active caspase-3 in vivo was likely attributable to slow binding, as demonstrated with in vitro inhibition kinetics. Hence, a second generation of caspase-3 selective ABPs was developed based on the Ac-ATS010-KE (Ac-3Pal-Asp-Phe(F5)-Phe-Asp-KE) with greatly improved binding kinetics over Ac-DW3-KE. Our probes based on Ac-ATS010-KE were made by modifying the N-terminus with 6 different linkers. All the linker modifications had limited effect on the binding kinetics, target selectivity, and pharmacokinetic profile in healthy mice. In an in vitro apoptosis model, the least hydrophilic tracer [18F]MICA-316 showed an increased uptake in apoptotic cells in comparison to the control group. Finally, [18F]MICA-316 was tested in an in vivo colorectal cancer model, where it showed a limited tumour uptake and was unable to discriminate treated tumours from the untreated group, despite demonstrating that the radiotracer was able to bind caspase-3 in complex mixtures in vitro. In contrast, the phosphatidylethanolamine (PE)-binding radiotracer [99mTc]Tc-duramycin was able to recognize the increased cell death in the disease model, making it the best performing treatment response assessment tracer developed thus far. Conclusions: In conclusion, a novel library of caspase-3-binding PET tracers retaining similar binding kinetics as the original inhibitor was developed. The most promising tracer, [18F]MICA-316, showed an increase uptake in an in vitro apoptosis model and was able to selectively bind caspase-3 in apoptotic tumour cells. In order to distinguish therapy-responsive from non-responsive tumours, the next generation of caspase-3-selective ABPs will be developed with higher tumour accumulation and in vivo stability. [ABSTRACT FROM AUTHOR]

Abstract Background The cysteine-aspartic acid protease caspase-3 is recognized as the main executioner of apoptosis in cells responding to specific extrinsic and intrinsic stimuli. Caspase-3 represents an interesting biomarker to evaluate treatment response, as many cancer therapies exert their effect by inducing tumour cell death. Previously developed caspase-3 PET tracers were unable to reach routine clinical use due to low tumour uptake or lack of target selectivity, which are two important requirements for effective treatment response evaluation in cancer patients. Therefore, the goal of this study was to develop and preclinically evaluate novel caspase-3-selective activity-based probes (ABPs) for apoptosis imaging. Results A library of caspase-3-selective ABPs was developed for tumour apoptosis detection. In a first attempt, the inhibitor Ac-DW3-KE (Ac-3Pal-Asp-βhLeu-Phe-Asp-KE) was 18F-labelled on the N-terminus to generate a radiotracer that was incapable of adequately detecting an increase in apoptosis in vivo. The inability to effectively detect active caspase-3 in vivo was likely attributable to slow binding, as demonstrated with in vitro inhibition kinetics. Hence, a second generation of caspase-3 selective ABPs was developed based on the Ac-ATS010-KE (Ac-3Pal-Asp-Phe(F5)-Phe-Asp-KE) with greatly improved binding kinetics over Ac-DW3-KE. Our probes based on Ac-ATS010-KE were made by modifying the N-terminus with 6 different linkers. All the linker modifications had limited effect on the binding kinetics, target selectivity, and pharmacokinetic profile in healthy mice. In an in vitro apoptosis model, the least hydrophilic tracer [18F]MICA-316 showed an increased uptake in apoptotic cells in comparison to the control group. Finally, [18F]MICA-316 was tested in an in vivo colorectal cancer model, where it showed a limited tumour uptake and was unable to discriminate treated tumours from the untreated group, despite demonstrating that the radiotracer was able to bind caspase-3 in complex mixtures in vitro. In contrast, the phosphatidylethanolamine (PE)-binding radiotracer [99mTc]Tc-duramycin was able to recognize the increased cell death in the disease model, making it the best performing treatment response assessment tracer developed thus far. Conclusions In conclusion, a novel library of caspase-3-binding PET tracers retaining similar binding kinetics as the original inhibitor was developed. The most promising tracer, [18F]MICA-316, showed an increase uptake in an in vitro apoptosis model and was able to selectively bind caspase-3 in apoptotic tumour cells. In order to distinguish therapy-responsive from non-responsive tumours, the next generation of caspase-3-selective ABPs will be developed with higher tumour accumulation and in vivo stability.

Positron emission tomography combined with computed tomography (PET/CT) is currently the standard imaging method in neuro-oncology for gliomas and metastatic lesions. There is much less experience with the use of PET/CT in meningioma, the most common primary tumor of the central nervous system, and there are some differences in how results are interpreted. The aim of the present work was to assess the potential for and features of the use of PET/CT to determine the degree of malignancy of meningioma, its prevalence, responses to radiotherapy, and diagnosis of relapse and/or post-radiation changes based on our own clinical experience and review of the literature. The study included 70 patients with 77 meningiomas who underwent 11C-methionine PET/CT. Mean age at investigation was 57.4 years (range 19–86 years). The main parameter evaluated, the tumor/normal ratio (T/N) of 11C-methionine (11C-MET) in tumors, averaged 3.13 (1.00–10.66). Meningiomas had high 11C-MET T/N, with values of >1.5 in 89.6% of cases. In histologically verified malignancy grade 1, 2, and 3 meningiomas (WHO scale), median T/N values were 4.06 [3.04; 4.57], 2.32 [2.12; 3.69], and 4.29 [2.60; 5.10] respectively, with no significant between-group differences. At the same time, non-growing or slowly growing histologically unverified meningiomas, i.e., incidentally discovered, had significantly lower 11C-MET T/N than grade 1 and 3 meningiomas. There was no significant difference in T/N between irradiated meningiomas with controls for tumor growth (3.81 [2.97, 3.98]) and relapse (3.62 [2.60, 4.30]). Comparison of irradiated and non-irradiated grade 1, 2, and 3 meningiomas, as well as the combined group of grade 1–3 tumors, revealed no significant differences in 11C-MET T/N. The use of PET/CT for meningiomas has a number of important characteristics. Meningiomas had high 11C-MET T/N. Our data indicate that 11C-MET PET/CT does not distinguish between meningiomas with different degrees of malignancy, i.e., WHO grades 1, 2, and 3. 11C-MET T/N in meningiomas remains stably high or shows a slight decrease in cases with effective radiotherapy and long-term local control. Comparison of growing and non-growing meningiomas revealed no significant differences in 11C-MET T/N between irradiated and non-irradiated tumors. [ABSTRACT FROM AUTHOR]

With advancements in hardware and software, non-destructive radiometric analytical methods have become popular in a wide range of applications. A typical case is the study of the leaching process of metals from mineral ores and mine tailings. The objective of the current study was to develop a radiometric method based on neutron activation analysis (NAA), in particular, delayed gamma neutron activation analysis (DGNAA), to monitor the process of Mn and Zn leaching from Ti ore, Cu mine tailings, and Zn-Pb mine tailings. The DGNAA method was performed using a neutron source: a deuterium-tritium (D-T) neutron generator for Mn and a MARIA research nuclear reactor for Zn. Laboratory-scale Mn leaching from Ti ores, Cu tailings, and Zn-Pb tailings was investigated using delayed gamma-rays of 56Mn (half-life of 2.6 h). The dissolution efficiencies of Mn were found to increase with interaction time and HCl concentration (1 to 5 M) and to vary with the leaching temperature (22.5 to 110 °C). Such results were found to agree with those obtained by total reflection X-ray fluorescence (TXRF) spectrometry for the same samples. 65Zn (half-life of 244 days) was chosen to investigate real-time/online leaching of Zn in Ti ore, Cu tailings, and Zn-Pb tailings. During online monitoring, Zn recovery was also reported to increase with increased leaching time. After approximately 300 min of leaching, 80%, 79%, and 53% recovery of Zn in Zn-Pb tailings, Ti ore, and Cu tailings, respectively, were reported. Theoretically, developed mathematical prediction models for 65Zn radiotracer analysis showed that the spherical diffusion model requires much less time to attain saturation compared to the linear diffusion model. The results of NAA for Zn were compared with those obtained by handheld X-ray fluorescence (handheld-XRF) and TXRF analysis. The analyzed samples encompassed leached Ti ore, Cu tailings, and Zn-Pb tailings which were subjected to different conditions of leaching time, temperature, and HCl concentrations. The XRF analysis confirmed that the leaching efficiencies of Zn rise with the increase in leaching time and HCl concentration and fluctuate with leaching temperature. The developed approach is important and can be applied in laboratories and industrial setups for online monitoring of the recovery of any element whose isotopes can be activated using neutrons. The efficiency of the metal-recovery process has a direct impact on the normal operation and economic advantages of hydrometallurgy. [ABSTRACT FROM AUTHOR]

Tumour hypoxia is a known microenvironmental culprit for treatment resistance, tumour recurrence and promotion of metastatic spread. Despite the long-known existence of this factor within the tumour milieu, hypoxia is still one of the greatest challenges in cancer management. The transition from invasive and less reliable detection methods to more accurate and non-invasive ways to identify and quantify hypoxia was a long process that eventually led to the promising results showed by functional imaging techniques. Hybrid imaging, such as PET-CT, has the great advantage of combining the structural or anatomical image (offered by CT) with the functional or metabolic one (offered by PET). However, in the context of hypoxia, it is only the PET image taken after appropriate radiotracer administration that would supply hypoxia-specific information. To overcome this limitation, the development of the latest hybrid imaging systems, such as PET-MRI, enables a synergistic approach towards hypoxia imaging, with both methods having the potential to provide functional information on the tumour microenvironment. This study is designed as a systematic review of the literature on the newest developments of PET-MRI for the imaging of hypoxic cells in breast cancer. The analysis includes the affinity of various PET-MRI tracers for hypoxia in this patient group as well as the correlations between PET-specific and MRI-specific parameters, to offer a broader view on the potential for the widespread clinical implementation of this hybrid imaging technique. [ABSTRACT FROM AUTHOR]

Neuroinflammation is associated with the pathophysiologies of neurodegenerative and psychiatric disorders. Evaluating neuroinflammation using positron emission tomography (PET) plays an important role in the early diagnosis and determination of proper treatment of brain diseases. To quantify neuroinflammatory responses in vivo, many PET tracers have been developed using translocator proteins, imidazole-2 binding site, cyclooxygenase, monoamine oxidase-B, adenosine, cannabinoid, purinergic P2X7, and CSF-1 receptors as biomarkers. In this review, we introduce the latest developments in PET tracers that can image neuroinflammation, focusing on clinical trials, and further consider their current implications. [ABSTRACT FROM AUTHOR]

Carbon‐11 (11C) is a widely used radionuclide for positron emission tomography (PET) owing to the omnipresence of carbon atoms in organic molecules. While its half‐life of 20.4 min is ideal for imaging and dosimetry, it also limits the synthetic possibilities. As such, the development of fast and easy, high‐yielding synthesis methods is crucial for the application of 11C‐labeled tracers in humans. In this study, we present a novel and efficient method for the reaction of [11C]CO2 with amine precursors using benzotriazole‐1‐yl‐oxy‐tris‐(dimethylamino)‐phosphonium hexafluorophosphate (BOP) to access 11C‐labeled ureas. Our method is extremely fast as it only requires transfer of [11C]CO2 into a solution with precursor and BOP at room temperature, where it reacts momentary into the desired 11C‐labeled urea. This simple procedure makes it possible to radiolabel urea directly from [11C]CO2 without the need for advanced equipment, making the method applicable for all laboratories where [11C]CO2 is available. We synthesized a small series of aliphatic symmetrical and non‐symmetrical 11C‐labeled ureas using this method, and achieved good to excellent yields. The novelty of our study lies in the fact that peptide coupling reagent BOP is used for the first time in radiochemistry to activate [11C]CO2, facilitating its reaction with amines to obtain 11C‐labeled ureas. [ABSTRACT FROM AUTHOR]

Purpose: Programmed cell death protein ligand 1 (PD-L1) is a crucial biomarker for immunotherapy. However, nearly 70% of patients do not respond to PD-L1 immune checkpoint therapy. Accurate monitoring of PD-L1 expression and quantification of target binding during treatment are essential. In this study, a series of small-molecule radiotracers were developed to assess PD-L1 expression and direct immunotherapy. Methods: Radiotracers of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were designed based on a 2-methyl-3-biphenyl methanol scaffold and successfully synthesized. Cellular experiments and molecular docking assays were performed to determine their specificity for PD-L1. PD-L1 status was investigated via positron emission tomography (PET) imaging in MC38 tumor models. PET imaging of [68Ga]Ga-D-pep-PMED was performed to noninvasively quantify PD-L1 blocking using an anti-mouse PD-L1 antibody (PD-L1 mAb). Results: The radiosyntheses of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were achieved with radiochemical yields of 87 ± 6%, 82 ± 4%, and 79 ± 9%, respectively. In vitro competition assays demonstrated their high affinities (the IC50 values of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were 90.66 ± 1.24, 160.8 ± 1.35, and 51.6 ± 1.32 nM, respectively). At 120 min postinjection (p.i.) of the radiotracers, MC38 tumors displayed optimized tumor-to-muscle ratios for all radioligands. Owing to its hydrophilic modification, [68Ga]Ga-D-pep-PMED had the highest target-to-nontarget (T/NT) ratio of approximately 6.2 ± 1.2. Interestingly, the tumor/liver ratio was hardly affected by different concentrations of the inhibitor BMS202. We then evaluated the impacts of dose and time on accessible PD-L1 levels in the tumor during anti-mouse PD-L1 antibody treatment. The tumor uptake of [68Ga]Ga-D-pep-PMED significantly decreased with increasing PD-L1 mAb dose. Moreover, after 8 days of treatment with a single antibody, the uptake of [68Ga]Ga-D-pep-PMED in the tumor significantly increased but remained lower than that in the saline group. Conclusion: PET imaging with [68Ga]Ga-D-pep-PMED, a small-molecule radiotracer, is a promising tool for evaluating PD-L1 expression and quantifying the target blockade of PD-L1 to assist in the development of effective therapeutic regimens. [ABSTRACT FROM AUTHOR]

Simple Summary: Neuroendocrine neoplasms are a heterogeneous group of malignant tumors that originate from the diffuse endocrine system. They generally have a slow course and somatostatin receptor-targeted based management is the first line of treatment. However, high-grade tumors and neuroendocrine carcinomas have a poor prognosis and somatostatin receptor-targeted therapy is not effective. The membrane receptor CXCR4 has been studied in several neoplasms and it is known to be overexpressed in aggressive tumors and associated with a worse prognosis. However, there is a lack of evidence of its use in neuroendocrine neoplasms. For that reason, this review describes the significance of CXCR4 and its possible clinical applications in the diagnostic and therapeutic management of neuroendocrine neoplasms. There are several well-described molecular mechanisms that influence cell growth and are related to the development of cancer. Chemokines constitute a fundamental element that is not only involved in local growth but also affects angiogenesis, tumor spread, and metastatic disease. Among them, the C-X-C motif chemokine ligand 12 (CXCL12) and its specific receptor the chemokine C-X-C motif receptor 4 (CXCR4) have been widely studied. The overexpression in cell membranes of CXCR4 has been shown to be associated with the development of different kinds of histological malignancies, such as adenocarcinomas, epidermoid carcinomas, mesenchymal tumors, or neuroendocrine neoplasms (NENs). The molecular synapsis between CXCL12 and CXCR4 leads to the interaction of G proteins and the activation of different intracellular signaling pathways in both gastroenteropancreatic (GEP) and bronchopulmonary (BP) NENs, conferring greater capacity for locoregional aggressiveness, the epithelial–mesenchymal transition (EMT), and the appearance of metastases. Therefore, it has been hypothesized as to how to design tools that target this receptor. The aim of this review is to focus on current knowledge of the relationship between CXCR4 and NENs, with a special emphasis on diagnostic and therapeutic molecular targets. [ABSTRACT FROM AUTHOR]

Abstract Colony‐stimulating factor 1 receptor (CSF1R) is highly expressed in mononuclear phagocytes and in the central nervous system. It has emerged as a promising target for tumor therapy and neuroinflammation imaging. Although therapeutic agents targeting CSF1R have shown great success, the development of diagnostic radiotracers for CSF1R has faced numerous challenges. Consequently, there is an urgent need to overcome these obstacles for the development of CSF1R radiotracers, particularly positron emission tomography tracers, not only for diagnostic purposes but also to aid the development of more effective therapeutic drugs. Here, we provide a comprehensive overview of the development of CSF1R radiotracers, presenting detailed profiles of each tracer's ability to image CSF1R. Additionally, we discuss reported CSF1R small‐molecule inhibitors and antibodies, highlighting their relevance to the further development of CSF1R radiotracers. We aim to shed light on the current state of CSF1R radiotracer research and development, provide an insight into the challenges in this field, and offer guidance for future exploration.

To overcome the limitations of current nano/micro-scale drug delivery systems, an Escherichia coli (E. coli)-based drug delivery system could be a potential alternative, and an effective tumor-targeting delivery system can be developed by attempting to perform chemical binding to the primary amine group of a cell membrane protein. In addition, positron emission tomography (PET) is a representative non-invasive imaging technology and is actively used in the field of drug delivery along with radioisotopes capable of long-term tracking, such as zirconium-89 (89Zr). The membrane proteins were labeled with 89Zr using chelate (DFO), and not only was the long-term biodistribution in tumors and major organs evaluated in the body, but the labeling stability of 89Zr conjugated to the membrane proteins was also evaluated through continuous tracking. E. coli accumulated at high levels in the tumor within 5 min (initial time) after tail intravenous injection, and when observed after 6 days, 89Zr-DFO on the surface of E. coli was found to be stable for a long period of time in the body. In this study, we demonstrated the long-term biodistribution and tumor-targeting effect of an E. coli-based drug delivery system and verified the in vivo stability of radioisotopes labeled on the surface of E. coli. [ABSTRACT FROM AUTHOR]

Tumor diagnosis, especially at the early stages, holds immense significance. Focal adhesion kinase (FAK) is often highly expressed across various types of tumors, making it a promising target for both therapy and diagnosis. In this study, seven novel inhibitors were designed and synthesized. The inhibitory activity of these compounds against FAK was notably potent, with an IC50 range of 1.27–1968 nM. In particular, compounds 7a and 7c, with IC50 values of 5.59 nM and 1.27 nM, respectively, were radiolabeled with F-18 and then evaluated with S-180 tumor-bearing mice. Subsequently, they exhibited moderate-to-high tumor uptake values, with [18F]7a showing 1.39 ± 0.30%ID/g at 60 min post injection and [18F]7c demonstrating 6.58 ± 0.46%ID/g at 30 min post injection. In addition, the results from docking studies revealed the binding specifics of the studied compounds. Overall, these findings hold the potential to offer valuable guidance for enhancing the development of radiotracers and enzyme inhibitors. [ABSTRACT FROM AUTHOR]

Purpose: Preclinical studies showed the tryptophan analog PET radiotracer 1-(2-18F-fluoroethyl)-L-tryptophan (18F-FETrp) to accumulate in various tumors, including gliomas, and being metabolized via the immunosuppressive kynurenine pathway. In this first-in-human study, we tested the use 18F-FETrp-PET in patients with neuroendocrine and brain tumors. Procedures: We applied dynamic brain imaging in patients with gliomas (n = 2) and multi-pass 3D whole-body PET scans in patients with neuroendocrine tumors (n =4). Semiquantitative analysis of organ and tumor tracer uptake was performed using standardized uptake values (SUVs). In addition, organ dosimetry was performed based on extracted time–activity curves and the OLINDA software. Results: Neuroendocrine tumors showed an early peak (10-min post-injection) followed by washout. Both gliomas showed prolonged 18F-FETrp accumulation plateauing around 40 min and showing heterogeneous uptake including non-enhancing tumor regions. Biodistribution showed moderate liver uptake and fast clearance of radioactivity into the urinary bladder; the estimated effective doses were similar to other 18F-labeled radioligands. Conclusions: The study provides proof-of-principle data for the safety and potential clinical value of 18F-FETrp-PET for molecular imaging of human gliomas. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzymes (ACE) are well-known for their roles in both blood pressure regulation via the renin-angiotensin system as well as functions in fertility, immunity, hematopoiesis, and many others. The two main isoforms of ACE include ACE and ACE-2 (ACE2). Both isoforms have similar structures and mediate numerous effects on the cardiovascular system. Most remarkably, ACE2 serves as an entry receptor for SARS-CoV-2. Understanding the interaction between the virus and ACE2 is vital to combating the disease and preventing a similar pandemic in the future. Noninvasive imaging techniques such as positron emission tomography and single photon emission computed tomography could noninvasively and quantitatively assess in vivo ACE2 expression levels. ACE2-targeted imaging can be used as a valuable tool to better understand the mechanism of the infection process and the potential roles of ACE2 in homeostasis and related diseases. Together, this information can aid in the identification of potential therapeutic drugs for infectious diseases, cancer, and many ACE2-related diseases. The present review summarized the state-of-the-art radiotracers for ACE2 imaging, including their chemical design, pharmacological properties, radiochemistry, as well as preclinical and human molecular imaging findings. We also discussed the advantages and limitations of the currently developed ACE2-specific radiotracers.

The short-lived positron-emitter carbon-11 (t1/2 = 20.4 min; β+, 99.8%) is prominent for labeling tracers for use in biomedical research with positron emission tomography (PET). Carbon-11 is produced for this purpose with a cyclotron, nowadays almost exclusively by the 14N(p,α)11C nuclear reaction, either on nitrogen containing a low concentration of oxygen (0.1–0.5%) or hydrogen (~5%) to produce [11C]carbon dioxide or [11C]methane, respectively. These primary radioactive products can be produced in high yields and with high molar activities. However, only [11C]carbon dioxide has some utility for directly labeling PET tracers. Primary products are required to be converted rapidly and efficiently into secondary labeling synthons to provide versatile radiochemistry for labeling diverse tracer chemotypes at molecular positions of choice. This review surveys known gas phase transformations of carbon-11 and summarizes the important roles that many of these transformations now play for producing a broad range of labeling synthons in carbon-11 chemistry. [ABSTRACT FROM AUTHOR]

Pollen allergens pose a significant health burden, affecting up to 30 $ \% $ % of the population in industrialized countries (Pablos, I.; Wildner, S.; Asam, C.; Wallner, M.; Gadermaier, G. Pollen Allergens for Molecular Diagnosis. Curr. Allergy Asthma Rep.2016,16, 1–12). With sizes typically ranging from 15 to $ 150\,\mu $ 150 μ mm (Wafaa, K.T. Pollen Allergens of some Road Trees, Shrubs and Herbs in Alexandria, Egypt. OAJBS.ID.000143, 2020), they can be filtered out of the air. However, recent studies have revealed that many pollen allergens are transported in free vesicles called pollensomes (Prado, N.; de Linares, C.; Sanz, M.L.; Gamboa, P.; Villalba, M.; Rodríguez, R.; Batanero, E. Pollensomes as Natural Vehicles for Pollen Allergens. J. Immun. (Balt., Md. : 1950)2015,195, 445–449, Rutter, B.D.; Innes, R.W. Extracellular Vesicles as Key Mediators of Plant-Microbe Interactions. Curr. Opin. Plant Biol.2018,44, 16–22). These vesicles, which have a much smaller size of approximately 28–60 nm (Prado, N.; de Linares, C.; Sanz, M.L.; Gamboa, P.; Villalba, M.; Rodríguez, R.; Batanero, E. Pollensomes as Natural Vehicles for Pollen Allergens. J. Immun. (Balt., Md. : 1950)2015,195, 445–449), cannot be retained by conventional filters. However, novel filter materials have been developed (Gotschall, K. Personal Communication; KLAVEGO GmbH & Co KG, 2022) which are capable of binding even such small protein structures selectively. Standard test methods exist for determining the retention efficiency for common filter technologies. However, these methods cannot be directly applied to the aforementioned nanoparticles. This limitation arises from the fact that the particle concentration of the filtered gas is often too low for conventional aerosol measurement devices to yield meaningful results. In this study, a novel test procedure using a solution of bovine serum albumin (BSA) labeled with radioactive iodine (I-131) is developed to determine the retention efficiency of filters by a highly sensitive radiotracer technique. [ABSTRACT FROM AUTHOR]

Primary components of sodium cooled fast reactors get contaminated due to activity transport that occurs from core to out-of-core through coolant which causes activity burden to the personnel during operation and maintenance. To minimize the MAN-REM issues it is necessary to scavenge 54Mn, 60Co and 65Zn which are of major radiological concern from primary sodium using a compact device. Experimental studies were performed at various durations and temperatures with nickel as single trap material to trap the radionuclides simultaneously and its uptake was estimated. Trapping efficiency of porous and non-porous Ni at 773 K was estimated using radiotracer technique. [ABSTRACT FROM AUTHOR]

Accurately identifying the peripheral pain generator in patients with chronic pain remains a major challenge for modern medicine. Millions of patients around the world suffer endlessly from difficult-to-manage debilitating pain because of very limited diagnostic tests and a paucity of pain therapies. To help these patients, we have developed a novel clinical molecular imaging approach, and, in its early stages, it has been shown to accurately identify the exact site of pain generation using an imaging biomarker for the sigma-1 receptor and positron emission tomography/magnetic resonance imaging. We hope the description of the work in this article can help others begin their own pain imaging programs at their respective institutions. [ABSTRACT FROM AUTHOR]

A novel gas chromatography method was developed using automatic injections to identify and quantify the amount of residual solvents or analytes in samples of fluorine-18 and carbon-11 radiopharmaceuticals. This approach evaluates seven analytes in less than 5 versus 13 min of acquisition time. The method additionally includes a 3 min bakeout to aid in the removal and carry-over of higher-boiling impurities. Chromatographic parameters such as column temperature, hold time, column pressure, flow rate, and split ratios were adjusted and optimized to analyze radioactive drug samples containing analytes which include methanol, ethanol, acetone, acetonitrile, triethylamine, N,N-dimethylformamide, and dimethyl sulfoxide. The relative standard deviation for each solvent was determined to be no greater than 1.6%. The method limit of detection (LOD) and limit of quantification (LOQ) were between 0.053 and 0.163 and 0.000 (5.791 × 10−6) and 0.520 mg/mL, respectively. This GC technique, using flame ionization detection (FID), was validated and is currently employed for the routine quality control of all approved IND and RDRC PET radiopharmaceuticals at our center. [ABSTRACT FROM AUTHOR]

With advancements in hardware and software, non-destructive radiometric analytical methods have become popular in a wide range of applications. A typical case is the study of the leaching process of metals from mineral ores and mine tailings. The objective of the current study was to develop a radiometric method based on neutron activation analysis (NAA), in particular, delayed gamma neutron activation analysis (DGNAA), to monitor the process of Mn and Zn leaching from Ti ore, Cu mine tailings, and Zn-Pb mine tailings. The DGNAA method was performed using a neutron source: a deuterium-tritium (D-T) neutron generator for Mn and a MARIA research nuclear reactor for Zn. Laboratory-scale Mn leaching from Ti ores, Cu tailings, and Zn-Pb tailings was investigated using delayed gamma-rays of 56Mn (half-life of 2.6 h). The dissolution efficiencies of Mn were found to increase with interaction time and HCl concentration (1 to 5 M) and to vary with the leaching temperature (22.5 to 110 °C). Such results were found to agree with those obtained by total reflection X-ray fluorescence (TXRF) spectrometry for the same samples. 65Zn (half-life of 244 days) was chosen to investigate real-time/online leaching of Zn in Ti ore, Cu tailings, and Zn-Pb tailings. During online monitoring, Zn recovery was also reported to increase with increased leaching time. After approximately 300 min of leaching, 80%, 79%, and 53% recovery of Zn in Zn-Pb tailings, Ti ore, and Cu tailings, respectively, were reported. Theoretically, developed mathematical prediction models for 65Zn radiotracer analysis showed that the spherical diffusion model requires much less time to attain saturation compared to the linear diffusion model. The results of NAA for Zn were compared with those obtained by handheld X-ray fluorescence (handheld-XRF) and TXRF analysis. The analyzed samples encompassed leached Ti ore, Cu tailings, and Zn-Pb tailings which were subjected to different conditions of leaching time, temperature, and HCl concentrations. The XRF analysis confirmed that the leaching efficiencies of Zn rise with the increase in leaching time and HCl concentration and fluctuate with leaching temperature. The developed approach is important and can be applied in laboratories and industrial setups for online monitoring of the recovery of any element whose isotopes can be activated using neutrons. The efficiency of the metal-recovery process has a direct impact on the normal operation and economic advantages of hydrometallurgy.

Tumour hypoxia is a known microenvironmental culprit for treatment resistance, tumour recurrence and promotion of metastatic spread. Despite the long-known existence of this factor within the tumour milieu, hypoxia is still one of the greatest challenges in cancer management. The transition from invasive and less reliable detection methods to more accurate and non-invasive ways to identify and quantify hypoxia was a long process that eventually led to the promising results showed by functional imaging techniques. Hybrid imaging, such as PET-CT, has the great advantage of combining the structural or anatomical image (offered by CT) with the functional or metabolic one (offered by PET). However, in the context of hypoxia, it is only the PET image taken after appropriate radiotracer administration that would supply hypoxia-specific information. To overcome this limitation, the development of the latest hybrid imaging systems, such as PET-MRI, enables a synergistic approach towards hypoxia imaging, with both methods having the potential to provide functional information on the tumour microenvironment. This study is designed as a systematic review of the literature on the newest developments of PET-MRI for the imaging of hypoxic cells in breast cancer. The analysis includes the affinity of various PET-MRI tracers for hypoxia in this patient group as well as the correlations between PET-specific and MRI-specific parameters, to offer a broader view on the potential for the widespread clinical implementation of this hybrid imaging technique.

Abstract Background Accumulating studies have demonstrated that elevated TIGIT expression in tumor microenvironment correlates with better therapeutic response to TIGIT-based immunotherapy in pre-clinical studies. Therefore, a non-invasive method to detect tumor TIGIT expression is crucial to predict the therapeutic effect. Methods In this study, a peptide-based PET imaging agent, 68Ga-DOTA-DTBP-3, was developed to non-invasively detect TIGIT expression by micro-PET in tumor-bearing BALB/c mice. DTBP-3, a D-peptide comprising of 12 amino acids, was radiolabeled with 68Ga through a DOTA chelator. In vitro studies were performed to evaluate the affinity of 68Ga-DOTA-DTBP-3 to TIGIT and its stability in fetal bovine serum. In vivo studies were assessed by micro-PET, biodistribution, and immunohistochemistry on tumor-bearing BALB/c mice. Results The in vitro studies showed the equilibrium dissociation constant of 68Ga-DOTA-DTBP-3 for TIGIT was 84.21 nM and its radiochemistry purity was 89.24 ± 1.82% in FBS at 4 h in room temperature. The results of micro-PET, biodistribution and immunohistochemistry studies indicated that 68Ga-DOTA-DTBP-3 could be specifically targeted in 4T1 tumor-bearing mice, with a highest uptake at 0.5 h. Conclusion 68Ga-DOTA-DTBP-3 holds potential for non-invasively detect tumor TIGIT expression and for timely assessment of the therapeutic effect of immune checkpoint blockade.

The Himalayas possess a distinctive topography owe to the dynamic interplay of tectonic activity, geological erosion and sedimentation, glacial processes, and climatic influences over the millions of years. The rugged, steep terrain and poor land management make it more prone to water erosion, negatively impacts the soil, affecting the goods and services supported by the soil ecosystems. Traditional methods used in soil erosion assessment face limitations when dealing with topographically complex hillslopes. The use of Fallout Radionuclide (FRN) -137Cs provides a feasible alternative for measurement of soil erosion in the region with such topography. However, there is lack of 137Cs-based soil erosion studies in the north-west Himalayas. Pine (Pinus roxburghii) is the predominant forest type in the Himalayas, offering numerous benefits to both natural ecosystems and human beings. In this study, we selected a typical steep hillslope covered with pine forest in the Himalayas for soil erosion assessment. The study measured 137Cs reference inventory of 1409 Bq m−2 in the landscape. Importantly, the concentration of 137Cs along the hillslope positions showed a significant variation attributed to topographic variability. Topographic factors, such as the slope shape and gradient, were identified as the major governing parameters of soil erosion in the hilly and mountainous region. The net soil erosion rate over hillslope positions revealed highest at upper hillslope followed by ridge, middle and valley hillslope positions. The net soil erosion rate under the pine forest ranged from 8.0 to 14.6 t ha−1 yr−1, with an average rate of 9.9 t ha−1 yr−1. Erosion rate over the hillslope positions were found in accordance to the soil loss tolerance limit (SLTL) except for the upper hillslope, indicating it as critical slope position requires to adopt suitable conservation measures. The study signifies the role of the forest in mitigating soil erosion and, in turn, conserving soil resources. The findings provide crucial insights and guidance to land managers and decision-makers, emphasizing the necessity of conserving and restoring forests in the Himalayas.

Tryptophan (Trp) is an essential proteinogenic amino acid and metabolic precursor for several signaling molecules that has been implicated in many physiological and pathological processes. Since the two main branches of Trp metabolism—serotonin biosynthesis and kynurenine pathway—are differently affected by a variety of neurological and neoplastic diseases, selective visualization of these pathways is of high clinical relevance. However, while positron emission tomography (PET) with existing probes can be used for non-invasive assessment of total Trp metabolism, optimal imaging agents for pathway-specific PET imaging are still lacking. In this work, we describe the preparation of two 18F-labeled Trp derivatives, NIn-methyl-6-[18F]fluorotryptophan (NIn-Me-6-[18F]FTrp) and 5-hydroxy-7-[18F]fluorotryptophan (5-HO-7-[18F]FTrp). We also report feasible synthetic routes for the preparation of the hitherto unknown boronate radiolabeling precursors and non-radioactive reference compounds. Under optimized conditions, alcohol-enhanced Cu-mediated radiofluorination of the respective precursors afforded NIn-Me-6-[18F]FTrp and 5-HO-7-[18F]FTrp as application-ready solutions in radiochemical yields of 45 ± 7% and 29 ± 4%, respectively. As such, our work provides access to two promising candidate probes for pathway-specific visualization of Trp metabolism in amounts sufficient for their preclinical evaluation. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme 2 (ACE2) is a cell-surface receptor that plays a critical role in the pathogenesis of SARS-CoV-2 infection. Through the use of ligands engineered for the receptor, ACE2 imaging has emerged as a valuable tool for preclinical and clinical research. These can be used to visualize the expression and distribution of ACE2 in tissues and cells. A variety of techniques including optical, magnetic resonance, and nuclear medicine contrast agents have been developed and employed in the preclinical setting. Positron-emitting radiotracers for highly sensitive and quantitative tomography have also been translated in the context of SARS-CoV-2-infected and control patients. Together this information can be used to better understand the mechanisms of SARS-CoV-2 infection, the potential roles of ACE2 in homeostasis and disease, and to identify potential therapeutic modulators in infectious disease and cancer. This review summarizes the tools and techniques to detect and delineate ACE2 in this rapidly expanding field. [ABSTRACT FROM AUTHOR]

Indian nuclear energy program adopts the closed fuel cycle, which involves reprocessing of the spent fuel and offers an option for the recovery of valuables from radioactive waste. Some of the useful isotopes present in radioactive wastes, of societal and industrial applications, are 137Cs, 90Sr, Platinum Groups Metals (PGMs: Pd, Rh, and Ru), 238Pu, 241Am, etc. Among PGMs, Ru is used in electrical, electrochemical industries and radioactive isotope of Ru is being applied for the treatment of eye cancer. In the present work, we are focusing on the pre-concentration of Ru from aqueous media by sorption method. Sorption studies were carried out using inactive Ru as well as its radiotracers. EDXRF, γ-ray spectrometry and spectrophotometry were used as the tools for monitoring the sorption processes. For preliminary studies, polyaniline and manganese dioxide were used as sorbents. The sorption was found to be better using polyaniline. For the ease of separation process, composite polymers of aniline with tetraethoxysilane were synthesized and used. The composites were characterized using SEM-EDS, FTIR and elemental analysis techniques. Sorption studies with and without presence of Zr were done with the aim of separation of radioactive Ru from irradiated Zr alloy and recovery of Ru. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of the study was to describe the surgical treatment of early-stage cervical cancer (CC) via minimally invasive surgery (MIS) and a sequential hybrid approach combining MIS and mini-Pfannenstiel. Evaluate sentinel lymph node (SLN) detection using a hybrid tracer (ICG-99m Tc nanocolloid). PATIENTS AND METHODS: Prospective, observational, descriptive, single-center study conducted at Son Espases University Hospital between January 2019 and September 2021. Patients with early-stage CC (FIGO 2018 IA1 with ILV-IIA1) who underwent surgical treatment with a follow-up of at least one year were included. RESULTS: Thirty early-stage CC patients were included, of whom four (13.3%) were upstaged due to positive SLNs. In these cases, laparotomy was avoided, and paraaortic lymphadenectomy was performed via MIS approach. Twenty-six patients had a radical hysterectomy: 15 underwent a hybrid approach, 10 laparoscopy, and one laparotomy. Patients undergoing laparoscopic surgery had a smaller estimated tumor size than those undergoing the hybrid approach. The overall SLN detection rate was 96.1%, with 88.5% of cases occurring bilaterally. Five out of 26 patients (19.2%) presented SLN macrometastases, and five (19.2%) had atypical drainage. Surgery refined staging in 33.3% (10/30) of cases. No recurrences were reported after an average follow-up of 32 months. CONCLUSIONS: MIS for SLN avoids laparotomy leading to rapid recovery and early adjuvant treatment initiation in nodal metastasis. In our study, tumor size is an important clinical implication in the surgical approach to be used. The hybrid tracer provided a high detection rate and combined the advantages of the two tracers. The hybrid approach has a quick recovery and optimal results. [ABSTRACT FROM AUTHOR]

Sentinel lymph node biopsy (SLNB) is a critical staging tool for melanoma patients. The optimal number of lymph nodes removed in SLNB remains unclear. In this study, we retrospectively analysed and tested different criteria for selecting sentinel lymph nodes (SLNs) by radiotracer uptake and blue dye, and their impact on nodal staging. We also evaluated the association between SLN tumour burden and radiotracer uptake. The study population consisted of melanoma patients undergoing SLNB. During the operation all radioactive and blue nodes were removed and sent for histopathological analysis. The ex vivo radioactive count and presence of blue dye of each node were recorded, and these were correlated with presence and size of metastasis in each SLN. Altogether 175 patients with clinically occult metastasis presented with one or more positive, i.e. metastatic, SLNs. The mean number of lymph nodes removed was 4.5, and the mean number of positive lymph nodes was 1.5 per patient. The most radioactive or hottest node was negative in 38 patients (22%). By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients would have been staged correctly. In five patients, metastasis was found solely in a SLN with radioactivity <10% of the hottest node. Of all 267 positive nodes removed, 125 (47%) contained blue dye. Patients with a negative hottest node were associated with lower SLN tumour burden. By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients with SLN metastases are correctly staged with or without using blue dye. [ABSTRACT FROM AUTHOR]

Sulphur uptake, sulphur derived from fertilizer (Sdff), S utilization, dry matter production and bunch yield of 'Robusta' banana (Musa x paradisiaca) under high density planting were studied on a sandy clay loam (Udic Paleustalf) soil at ICAR-Indian Institute of Horticultural Research, Bangalore using 35S labelled superphosphate applied in different split at early vegetative (I split), late vegetative (II split) and bud differentiation (III split)) stages and placement (15-35, 35-55 and 55-75 cm band width) from pseudostem of the plant. From the results, it is noteworthy that it was the first split application from which Sdff of 8.22% was observed compared to 3.31 and 0.94% from II and III split applications, respectively as observed from the isotope found in leaves from 20 to 80 days after application. However, in respect of total fertilizer utilized by plant, both I and II split applications contributed 39-40% while the III split application supplied 20% of the fertilizer sulphur to the plant. Higher dry matter production, fruit weight and bunch yield of 'Robusta' banana was recorded with I and II split application. Among the placements 15-35 and 35-55 cm placements showed an edge with the highest fruit weight, bunch weight and dry matter production over the farthest placement (55-75 cm). The experiments revealed that inter-plant competition of roots for nutrients was practically negligible. Leaf and fruit were the largest sinks (35.2 and 31.9%, respectively) for fertilizer sulphur while pseudo stem appropriated 15.8%. Application of recommended sulphur in 2 splits as circular bands at 5cm depth, between 15 and 35cm in the first and between 35 and 55cm distance from the base of the plant in the second split was optimal to attain high fruit and bunch yield in Robusta banana under high density planting. Application of fertilizer at the farthest distance between 55 and 75 cm distances was distinctly inferior showing that there is little scope of application of fertilizers between the rows under the high-density planting of banana. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is an imaging modality used for the noninvasive assessment of tumor staging and response to therapy. PET with 18F labeled fluorodeoxyglucose (18F-FDG PET) is widely used to assess the active and inactive lesions in patients with multiple myeloma (MM). Despite the availability of 18F-FDG PET for the management of MM, PET imaging is less sensitive than next-generation flow cytometry and sequencing. Therefore, the novel PET radiotracers 64Cu-LLP2A, 68Ga-pentixafor, and 89Zr-daratumumab have been developed to target the cell surface antigens of MM cells. Furthermore, recent studies attempted to visualize the tumor-infiltrating lymphocytes using PET imaging in patients with cancer to investigate their prognostic effect; however, these studies have not yet been performed in MM patients. This review summarizes the recent studies on PET with 18F-FDG and novel radiotracers for the detection of MM and the resulting preclinical research using MM mouse models and clinical studies. Novel PET technologies may be useful for developing therapeutic strategies for MM in the future. [ABSTRACT FROM AUTHOR]

The factors regulating potential acquisition of sulphur (S)-containing amino acids by plant roots from the rhizosphere remain poorly understood. Using radio tracer (14C and 35S), we studied the competition for two S-containing amino acids (i.e., cysteine (Cys) and methionine (Met)) within 24 hours (h), by the rhizosphere microbial community and maize plants (Zea mays L.). Our results showed that the capture of Cys and Met by the maize plants was much lower, with only <10% of the added amino acid-14C or 35S captured by the plant, compared to the rhizosphere microbial community (76.9%) on average. We suggest that this could be a result of relatively high availability of inorganic N and S in soil solution, the lack of transmembrane for amino acids on maize root cells, as well as the rapid turnover of Cys and Met by soil microbes in the rhizosphere. The addition of inorganic S, significantly reduced plant capture of Cys and Met-14C by maize plants in the rhizosphere but had little effect on the capture of Cys and Met-35S (p<0.05). Overall, our results imply that (1) Cys and Met are available carbon (C), nitrogen (N) and S sources for maize plants, potentially contributing to total plant N and S demand under certain conditions; (2) Utilization of Cys and Met by maize roots in the rhizosphere is independent of inorganic S availability; (3) Increased amino acid concentration led to higher capture by both plants and soil microbes, but had little effect on the competition success on either side. [ABSTRACT FROM AUTHOR]

To overcome the limitations of current nano/micro-scale drug delivery systems, an Escherichia coli (E. coli)-based drug delivery system could be a potential alternative, and an effective tumor-targeting delivery system can be developed by attempting to perform chemical binding to the primary amine group of a cell membrane protein. In addition, positron emission tomography (PET) is a representative non-invasive imaging technology and is actively used in the field of drug delivery along with radioisotopes capable of long-term tracking, such as zirconium-89 (89Zr). The membrane proteins were labeled with 89Zr using chelate (DFO), and not only was the long-term biodistribution in tumors and major organs evaluated in the body, but the labeling stability of 89Zr conjugated to the membrane proteins was also evaluated through continuous tracking. E. coli accumulated at high levels in the tumor within 5 min (initial time) after tail intravenous injection, and when observed after 6 days, 89Zr-DFO on the surface of E. coli was found to be stable for a long period of time in the body. In this study, we demonstrated the long-term biodistribution and tumor-targeting effect of an E. coli-based drug delivery system and verified the in vivo stability of radioisotopes labeled on the surface of E. coli.

Tumor diagnosis, especially at the early stages, holds immense significance. Focal adhesion kinase (FAK) is often highly expressed across various types of tumors, making it a promising target for both therapy and diagnosis. In this study, seven novel inhibitors were designed and synthesized. The inhibitory activity of these compounds against FAK was notably potent, with an IC50 range of 1.27–1968 nM. In particular, compounds 7a and 7c, with IC50 values of 5.59 nM and 1.27 nM, respectively, were radiolabeled with F-18 and then evaluated with S-180 tumor-bearing mice. Subsequently, they exhibited moderate-to-high tumor uptake values, with [18F]7a showing 1.39 ± 0.30%ID/g at 60 min post injection and [18F]7c demonstrating 6.58 ± 0.46%ID/g at 30 min post injection. In addition, the results from docking studies revealed the binding specifics of the studied compounds. Overall, these findings hold the potential to offer valuable guidance for enhancing the development of radiotracers and enzyme inhibitors.

To evaluate whether a learning curve affects the bilateral sentinel lymph node (SLN) detection in early-stage cervical cancer. All patients with FIGO (2018) stage IA1-IB2 or IIA1 cervical cancer who had undergone robot-assisted SLN mapping performed with a combination of preoperative technetium-99m nanocolloids (including preoperative imaging) and intraoperative blue dye were retrospectively included. Risk-adjusted cumulative sum (RA-CUSUM) analysis was used to determine if a learning curve based on bilateral SLN detection existed in this cohort. A total of 227 cervical cancer patients were included. In 98.2% of patients (223/227) at least one SLN was detected. The bilateral SLN detection rate was 87.2% (198/227). Except for age (OR 1.06 per year, 95%CI 1.02–1.09), no significant risk factors for non-bilateral SLN detection were found (e.g., prior conization, BMI or FIGO stage). The RA-CUSUM analysis showed no clear learning phase during the first procedures and cumulative bilateral detection rate remained at least 80% during the entire inclusion period. In this single-institution experience, we observed no learning curve affecting robot-assisted SLN mapping using a radiotracer and blue dye in early-stage cervical cancer patients, with stable bilateral detection rates of at least 80% when adhering to a standardized methodology. [ABSTRACT FROM AUTHOR]

Background: Accumulating studies have demonstrated that elevated TIGIT expression in tumor microenvironment correlates with better therapeutic response to TIGIT-based immunotherapy in pre-clinical studies. Therefore, a non-invasive method to detect tumor TIGIT expression is crucial to predict the therapeutic effect. Methods: In this study, a peptide-based PET imaging agent, 68Ga-DOTA-DTBP-3, was developed to non-invasively detect TIGIT expression by micro-PET in tumor-bearing BALB/c mice. DTBP-3, a D-peptide comprising of 12 amino acids, was radiolabeled with 68Ga through a DOTA chelator. In vitro studies were performed to evaluate the affinity of 68Ga-DOTA-DTBP-3 to TIGIT and its stability in fetal bovine serum. In vivo studies were assessed by micro-PET, biodistribution, and immunohistochemistry on tumor-bearing BALB/c mice. Results: The in vitro studies showed the equilibrium dissociation constant of 68Ga-DOTA-DTBP-3 for TIGIT was 84.21 nM and its radiochemistry purity was 89.24 ± 1.82% in FBS at 4 h in room temperature. The results of micro-PET, biodistribution and immunohistochemistry studies indicated that 68Ga-DOTA-DTBP-3 could be specifically targeted in 4T1 tumor-bearing mice, with a highest uptake at 0.5 h. Conclusion: 68Ga-DOTA-DTBP-3 holds potential for non-invasively detect tumor TIGIT expression and for timely assessment of the therapeutic effect of immune checkpoint blockade. [ABSTRACT FROM AUTHOR]

Simple Summary: PD-L1 plays a crucial role in the immune responses against cancer. Only around 30% of cancer patients respond to an anti-PD-L1 immune checkpoint inhibitor therapy. Noninvasive molecular imaging techniques such as positron emission tomography (PET) would allow identification of patients likely to respond. Here we report on the synthesis of nine PET radioligands targeting PD-L1, based on small-molecule inhibitors. We introduced a chelator for radiolabeling and water-soluble groups to aim for clearance through the kidneys. The compounds showed binding affinities toward PD-L1 in the lower nanomolar range and stability in vitro. Mouse experiments showed moderate accumulation in tumor tissue but mainly clearance through the liver. Additionally, the compounds showed unexpected long circulation times due to strong binding to albumin in blood. Nevertheless, our compounds are a starting point for further development of PD-L1 small molecule PET radiotracer to support therapy decisions. Noninvasive molecular imaging of the PD-1/PD-L1 immune checkpoint is of high clinical relevance for patient stratification and therapy monitoring in cancer patients. Here we report nine small-molecule PD-L1 radiotracers with solubilizing sulfonic acids and a linker–chelator system, designed by molecular docking experiments and synthesized according to a new, convergent synthetic strategy. Binding affinities were determined both in cellular saturation and real-time binding assay (LigandTracer), revealing dissociation constants in the single digit nanomolar range. Incubation in human serum and liver microsomes proved in vitro stability of these compounds. Small animal PET/CT imaging, in mice bearing PD-L1 overexpressing and PD-L1 negative tumors, showed moderate to low uptake. All compounds were cleared primarily through the hepatobiliary excretion route and showed a long circulation time. The latter was attributed to strong blood albumin binding effects, discovered during our binding experiments. Taken together, these compounds are a promising starting point for further development of a new class of PD-L1 targeting radiotracers. [ABSTRACT FROM AUTHOR]

Although the epigenetic regulatory protein histone deacetylase 6 (HDAC6) has been recently implicated in the etiology of Alzheimer's disease (AD), little is known about the role of HDAC6 in the etiopathogenesis of AD and whether HDAC6 can be a potential therapeutic target for AD. Here, we performed positron emission tomography (PET) imaging in combination with histopathological analysis to better understand the underlying pathomechanisms of HDAC6 in AD. We first developed [18F]PB118 which was demonstrated as a valid HDAC6 radioligand with excellent brain penetration and high specificity to HDAC6. PET studies of [18F]PB118 in 5xFAD mice showed significantly increased radioactivity in the brain compared to WT animals, with more pronounced changes identified in the cortex and hippocampus. The translatability of this radiotracer for AD in a potential human use was supported by additional studies, including similar uptake profiles in non-human primates, an increase of HDAC6 in AD-related human postmortem hippocampal tissues by Western blotting protein analysis, and our ex vivo histopathological analysis of HDAC6 in postmortem brain tissues of our animals. Collectively, our findings show that HDAC6 may lead to AD by mechanisms that tend to affect brain regions particularly susceptible to AD through an association with amyloid pathology.

Gliomas are the most common primary brain tumors in adults. A diffuse infiltrative growth pattern and high resistance to therapy make them largely incurable, but there are significant differences in the prognosis of patients with different subtypes of glioma. Mutations in isocitrate dehydrogenase (IDH) have been recognized as an important biomarker for glioma classification and a potential therapeutic target. However, current clinical methods for detecting mutated IDH (mIDH) require invasive tissue sampling and cannot be used for follow-up examinations or longitudinal studies. PET imaging could be a promising approach for non-invasive assessment of the IDH status in gliomas, owing to the availability of various mIDH-selective inhibitors as potential leads for the development of PET tracers. In the present review, we summarize the rationale for the development of mIDH-selective PET probes, describe their potential applications beyond the assessment of the IDH status and highlight potential challenges that may complicate tracer development. In addition, we compile the major chemical classes of mIDH-selective inhibitors that have been described to date and briefly consider possible strategies for radiolabeling of the most promising candidates. Where available, we also summarize previous studies with radiolabeled analogs of mIDH inhibitors and assess their suitability for PET imaging in gliomas. [ABSTRACT FROM AUTHOR]

Plastic waste is a solid that is difficult to decompose but can turn into environmental microplastics. Microplastics are sizes between 0.1 µm-5 mm, highly prolific anthropogenic pollutants affecting terrestrial, freshwater, and marine ecosystems. The purpose of this study was to determine the ability of Babylonia spirata to accumulate and eliminate polystyrene microplastics. This experiment uses the nuclear applications technique. The experiment consists of two methods: manufacturing microplastics and biokinetics. The manufacture of microplastics labeled Zn-65 is based on the reaction of polystyrene sulfonate with zinc to form polystyrene sulfonate Zn resin. This microplastic labeled Zn-65 is very stable in the aquatic environment, so it is used for bioaccumulation experiments. Biokinetics includes acclimatization/adaptation of the organism for seven days, bioaccumulation consists of the organism accumulating microplastics labeled Zn-65 for seven days, and depuration for seven days that were placing the organism accumulating microplastics labeled Zn-65 in water free of contamination and biokinetics calculations include the BCF (Biocontration Factor), ku (uptake constant), ke (depuration constants), and t1/2 (halflife). The experimental results show that the ability to bioaccumulate polystyrene microplastics from seawater (BCF) is 79.2 to 304.31 ml.g-1. This bioaccumulation is affected by the microplastic content in the water. The biological half-life of the microplastic is 14.54 to 41.78 d. There is a relationship between the concentration and the Ku, Ke and BCF. the polystyrene content. The experimental results show that microplastics bioaccumulate in a marine organism so that they can move through the food chain and are ultimately harmful to humans. [ABSTRACT FROM AUTHOR]

Sentinel lymph node (SLN) biopsy for cutaneous melanoma is a critical part of designing therapy for the skin malignancy. A retrospective review of 54 patients with cutaneous melanoma who underwent SLN biopsy guided by both radiotracer injection and indocyanine green (ICG) fluorescent dye compared the accuracy of identifying the SLN using each method. Patients were injected preoperatively with radiotracer at the site of the primary melanoma and intraoperatively with 2.5 mg of ICG. The detection of the SLN was compared between the two methods. Patients were followed to determine local recurrence and survival from 5 months to 4 years. ICG and radiotracer identified the SLN in 52 of 54 patients. In those patients who mapped, 52 of 52 showed mapping to the same node or nodes. The rate of cancer involvement in the identified node was 19.2% for both techniques. There was no difference in recurrence or survival between the two methods of SLN identification in short follow-up. In conclusion, ICG injection and mapping to identify SLN in cutaneous melanoma is confirmatory for radiotracer mapping and in the future may be an accurate and less costly method for SLN biopsy in cutaneous melanoma. [ABSTRACT FROM AUTHOR]

Theranostic approaches with positron emission tomography/computed tomography (PET/CT) or PET/magnetic resonance imaging (PET/MRI) molecular imaging probes are being implemented clinically in prostate cancer (PCa) diagnosis and imaging-guided precision surgery. This review article provides a comprehensive summary of the rapidly expanding list of molecular imaging probes in this field, including their applications in early diagnosis of primary prostate lesions; detection of lymph node, skeletal and visceral metastases in biochemical relapsed patients; and intraoperative guidance for tumor margin detection and nerve preservation. Although each imaging probe shows preferred efficacy in some applications and limitations in others, the exploration and research efforts in this field will eventually lead to improved precision theranostics of PCa. [ABSTRACT FROM AUTHOR]

In this work, we developed a novel approach to purify [11C]Raclopride ([11C]RAC), an important positron emission tomography radiotracer, based on tailored shape-recognition polymers, with the aim to substitute single-pass HPLC purification with an in-flow trap & release process. Molecular imprinting technology (MIT) applied to solid phase extraction (MISPE) was investigated to develop a setting able to selectively extract [11C]RAC in a mixture containing a high amount of its precursor, (S)-O-Des-Methyl-Raclopride (DM-RAC). Two imprinted polymers selective for unlabeled RAC and DM-RAC were synthesized through a radical polymerization at 65 °C using methacrylic acid and trimethylolpropane trimethacrylate in the presence of template molecule (RAC or DM-RAC). The prepared polymer was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy and tested in MISPE experiments. The polymers were used in testing conditions, revealing a high retention capacity of RAC-MISPE to retain RAC either in the presence of similar concentrations of RAC and DM-RAC precursor (96.9%, RSD 6.6%) and in the presence of a large excess of precursor (90%, RSD 4.6%) in the loading solution. Starting from these promising results, preliminary studies for selective purification of [11C]Raclopride using this RAC-MISPE were performed and, while generally confirming the selectivity capacity of the polymer, revealed challenging applicability to the current synthetic process, mainly due to high backpressures and long elution times. [ABSTRACT FROM AUTHOR]

The extraction of useful minerals or geological materials from the Earth's crust, most typically from various sources, is crucial to a country's development and progress. Mineral-rich countries use these resources to transform their economies and propel them toward long-term prosperity. There is an urgent need for the world to increase mineral exploration efforts, improve the recycling of important metal-containing resources, and extract them using upgraded hydrometallurgical procedures with high recovery efficiency. This review paper highlights the importance of strategic and critical metals in the economy and the role of nuclear techniques in the analysis, process optimization, and remediation of metals using solvent extraction, adsorption, and chromatographic resins. Radiotracer analysis, X-Ray Fluorescence spectrometry (XRF), Neutron Activation Analysis (NAA), and X-Ray Diffraction (XRD) are appropriate for improving laboratory-based hydrometallurgical processes, with future technical and economic benefits. The development and installation of novel instruments to provide the real-time control of mining and mineral processing plants for improved control have the potential to aid in the recovery of a broad range of metals. [ABSTRACT FROM AUTHOR]

The use of computer-aided drug design (CADD) for the identification of lead compounds in radiotracer development is steadily increasing. Traditional CADD methods, such as structure-based and ligand-based virtual screening and optimization, have been successfully utilized in many drug discovery programs and are highlighted throughout this review. First, we discuss the use of virtual screening for hit identification at the beginning of drug discovery programs. This is followed by an analysis of how the hits derived from virtual screening can be filtered and culled to highly probable candidates to test in in vitro assays. We then illustrate how CADD can be used to optimize the potency of experimentally validated hit compounds from virtual screening for use in positron emission tomography (PET). Finally, we conclude with a survey of the newest techniques in CADD employing machine learning (ML). [ABSTRACT FROM AUTHOR]