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Simple Summary: Pancreatic cancer is surrounded by a dense fibrotic environment due to the activity of pancreatic stellate cells (PSCs). This hinders the effectiveness of treatment by limiting drug penetration and oxygen delivery. To better understand this, PSCs and cancer cells were studied in laboratory models using radiotracer imaging techniques. The results indicated that while glucose uptake and hypoxia were similar between cancer cells alone and in combination with PSCs, a specific marker of fibrosis (FAPα) was significantly higher in PSC-rich environments. In mice, the marker in question decreased in tumors with only PSCs, indicating that the cells had died. Conversely, the biomarker increased over time in tumors containing both cancer cells and PSCs, suggesting that mouse cells had invaded. This study sheds light on how the tumor environment influences metabolism and thus provides insights for more targeted theranostic applications. In turn, this approach supports the development of more reliable models. Background/Objective Pancreatic stellate cells (PSCs) in pancreatic adenocarcinoma (PDAC) are producing extracellular matrix, which promotes the formation of a dense fibrotic microenvironment. This makes PDAC a highly heterogeneous tumor-stroma-driven entity, associated with reduced perfusion, limited oxygen supply, high interstitial fluid pressure, and limited bioavailability of therapeutic agents. Methods In this study, spheroid and tumor xenograft models of human PSCs and PanC-1 cells were characterized radiopharmacologically using a combined positron emission tomography (PET) radiotracer approach. [18F]FDG, [18F]FMISO, and [18F]FAPI-74 were employed to monitor metabolic activity, hypoxic metabolic state, and functional expression of fibroblast activation protein alpha (FAPα), a marker of activated PSCs. Results In vitro, PanC-1 and multi-cellular tumor spheroids demonstrated comparable glucose uptake and hypoxia, whereas FAPα expression was significantly higher in PSC spheroids. In vivo, glucose uptake as well as the transition to hypoxia were comparable in PanC-1 and multi-cellular xenograft models. In mice injected with PSCs, FAPα expression decreased over a period of four weeks post-injection, which was attributed to the successive death of PSCs. In contrast, FAPα expression increased in both PanC-1 and multi-cellular xenograft models over time due to invasion of mouse fibroblasts. Conclusion The presented models are suitable for subsequently characterizing stromal cell-induced metabolic changes in tumors using noninvasive molecular imaging techniques. [ABSTRACT FROM AUTHOR]

This review focuses on the pivotal role of radiotracers in breast cancer imaging, emphasizing their importance in accurate detection, staging, and treatment monitoring. Radiotracers, labeled with radioactive isotopes, are integral to various nuclear imaging techniques, including positron emission tomography (PET) and positron emission mammography (PEM). The most widely used radiotracer in breast cancer imaging is 18F-fluorodeoxyglucose (18F-FDG), which highlights areas of increased glucose metabolism, a hallmark of many cancer cells. This allows for the identification of primary tumors and metastatic sites and the assessment of tumor response to therapy. In addition to 18F-FDG, this review will explore newer radiotracers targeting specific receptors, such as estrogen receptors or HER2, which offer more personalized imaging options. These tracers provide valuable insights into the molecular characteristics of tumors, aiding in tailored treatment strategies. By integrating radiotracers into breast cancer management, clinicians can enhance early disease detection, monitor therapeutic efficacy, and guide interventions, ultimately improving patient outcomes. Ongoing research aimed at developing more specific and sensitive tracers will also be highlighted, underscoring their potential to advance precision medicine in breast cancer care. [ABSTRACT FROM AUTHOR]

Radioguidance that makes use of β-emitting radionuclides is gaining in popularity and could have potential to strengthen the range of existing radioguidance techniques. While there is a strong tendency to develop new PET radiotracers, due to favorable imaging characteristics and the success of theranostics research, there are practical challenges that need to be overcome when considering use of β-emitters for surgical radioguidance. In this position paper, the EANM identifies the possibilities and challenges that relate to the successful implementation of β-emitters in surgical guidance, covering aspects related to instrumentation, radiation protection, and modes of implementation. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Assessing the potential sources of bias and variability of the Centiloid (CL) scale is fundamental for its appropriate clinical application. METHODS: We included 533 participants from AMYloid imaging to Prevent Alzheimer's Disease (AMYPAD DPMS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) cohorts. Thirty‐two CL pipelines were created using different combinations of reference region (RR), RR and target types, and quantification spaces. Generalized estimating equations stratified by amyloid positivity were used to assess the impact of the quantification pipeline, radiotracer, age, brain atrophy, and harmonization status on CL. RESULTS: RR selection and RR type impact CL the most, particularly in amyloid‐negative individuals. The standard CL pipeline with the whole cerebellum as RR is robust against brain atrophy and differences in image resolution, with 95% confidence intervals below ± 3.95 CL for amyloid beta positivity cutoffs (CL < 24). DISCUSSION: The standard CL pipeline is recommended for most scenarios. Confidence intervals should be considered when operationalizing CL cutoffs in clinical and research settings. Highlights: We developed a framework for evaluating Centiloid (CL) variability to different factors.Reference region selection and delineation had the highest impact on CL values.Whole cerebellum (WCB) and whole cerebellum plus brainstem (WCB+BSTM) as reference regions yielded consistent results across tracers.The standard CL pipeline is robust against atrophy and image resolution variation.Estimated within‐ and between‐pipeline variability (95% confidence interval) in absolute CL units. [ABSTRACT FROM AUTHOR]

Radioactive materials may contain primordial radionuclides, and radionuclides of anthropogenic, nuclear accident, and waste disposal which are present in marine environments. This review explores various approaches for the effective sampling and detection of marine radionuclides. The different types of samples that can be collected, including water, sediment, biota, and suspended particulate matter are discussed. Additionally, this paper discusses the various analytical techniques employed for radionuclide detection, such as gamma spectrometry and radiochemical separation. The review emphasizes the importance of choosing appropriate sampling and detection methods based on the specific radionuclides, environmental conditions, and the desired level of sensitivity. It also highlights the challenges associated with their sampling and detection in complex marine environments. These include low radionuclide concentrations, interference from natural matrices, and contamination risks. [ABSTRACT FROM AUTHOR]

Fast and straightforward incorporation of radionuclides into pharmaceutically relevant molecules is one of the main barriers to preclinical and clinical tracer research. Late‐stage direct incorporation of cyclotron‐produced [11C]CO2 to afford carbon‐11‐labeled radiopharmaceuticals has the potential to provide ready‐to‐inject positron emission tomography agents in less than an hour. The present work describes photocatalyzed carboxylation of alkylbenzene derivatives to afford 11C‐phenylacetic acids. Reaction conditions and scope are investigated followed by application of this methodology to the preparative radiosynthesis of [11C]fenoprofen, a nonsteroidal anti‐inflammatory drug. [ABSTRACT FROM AUTHOR]

Dementia is a significant global health issue that is exacerbated by an aging population. Imaging plays an established role in the evaluation of patients with neurocognitive disorders such as dementia. In current clinical practice, magnetic resonance imaging (MRI) and positron emission tomography (PET) are primary imaging modalities used separately but in concert to help diagnose and classify dementia. The clinical applications of PET/MRI hybrid imaging in dementia are an active area of research, particularly given the continued emergence of functional MRI (fMRI) and amyloid PET tracers. This narrative review provides a comprehensive overview of the rationale and current evidence for PET/MRI hybrid dementia imaging from 2018 to 2023. Hybrid imaging offers advantages in the accuracy of characterizing neurodegenerative disorders, and future research will need to address the cost of integrated PET/MRI systems compared to stand-alone scanners, the development of new biomarkers, and image correction techniques. [ABSTRACT FROM AUTHOR]

This review focuses on the pivotal role of radiotracers in breast cancer imaging, emphasizing their importance in accurate detection, staging, and treatment monitoring. Radiotracers, labeled with radioactive isotopes, are integral to various nuclear imaging techniques, including positron emission tomography (PET) and positron emission mammography (PEM). The most widely used radiotracer in breast cancer imaging is 18F-fluorodeoxyglucose (18F-FDG), which highlights areas of increased glucose metabolism, a hallmark of many cancer cells. This allows for the identification of primary tumors and metastatic sites and the assessment of tumor response to therapy. In addition to 18F-FDG, this review will explore newer radiotracers targeting specific receptors, such as estrogen receptors or HER2, which offer more personalized imaging options. These tracers provide valuable insights into the molecular characteristics of tumors, aiding in tailored treatment strategies. By integrating radiotracers into breast cancer management, clinicians can enhance early disease detection, monitor therapeutic efficacy, and guide interventions, ultimately improving patient outcomes. Ongoing research aimed at developing more specific and sensitive tracers will also be highlighted, underscoring their potential to advance precision medicine in breast cancer care.

Microfluidic technology is a highly efficient technique used in positron emission tomography (PET) radiochemical synthesis. This approach enables the precise control of reactant flows and reaction conditions, leading to improved yields and reduced synthesis time. The synthesis of two radiotracers, L-[11C]methionine and [11C]choline, was performed, using a microfluidic cassette and an iMiDEVTM module by employing a dose-on-demand approach for the synthesis process. We focused on optimizing the precursor amounts and radiosynthesis on the microfluidic cassette. L-[11C]methionine and [11C]choline were synthesized using a microreactor filled with a suitable resin for the radiochemical reaction. Trapping of the [11C]methyl iodide, its reaction, and solid-phase extraction purification were performed on a microreactor, achieving radiochemical yields of >80% for L-[11C]methionine and >60% for [11C]choline (n = 3). The total synthesis time for both the radiotracers was approximately 20 min. All quality control tests complied with the European Pharmacopeia standards. The dose-on-demand model allows for real-time adaptation to patient schedules, making it suitable for preclinical and clinical settings. Precursor optimization enhanced the cost efficiency without compromising the yield. The importance of dose-on-demand synthesis and optimized precursor utilization to produce L-[11C]methionine and [11C]choline was emphasized in this study. The results demonstrated the feasibility of dose-on-demand adaptations for clinical applications with reduced precursor quantities and high radiochemical yields. [ABSTRACT FROM AUTHOR]

Background: The demand for 68Ga-labeled radiotracers has significantly increased in the past decade, driven by the development of diversified imaging tracers, such as FAPI derivatives, PSMA-11, DOTA-TOC, and DOTA-TATE. These tracers have exhibited promising results in theranostic applications, fueling interest in exploring them for clinical use. Among these probes, 68Ga-labeled FAPI-46 and DOTA-TOC have emerged as key players due to their ability to diagnose a broad spectrum of cancers ([68Ga]Ga-FAPI-46) in late-phase studies, whereas [68Ga]Ga-DOTA-TOC is clinically approved for neuroendocrine tumors. To facilitate their production, we leveraged a microfluidic cassette-based iMiDEV radiosynthesizer, enabling the synthesis of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC based on a dose-on-demand (DOD) approach. Results: Different mixing techniques were explored to influence radiochemical yield. We achieved decay-corrected yield of 44 ± 5% for [68Ga]Ga-FAPI-46 and 46 ± 7% for [68Ga]Ga-DOTA-TOC in approximately 30 min. The radiochemical purities (HPLC) of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC were 98.2 ± 0.2% and 98.4 ± 0.9%, respectively. All the quality control results complied with European Pharmacopoeia quality standards. We optimized various parameters, including 68Ga trapping and elution, cassette batches, passive mixing in the reactor, and solid-phase extraction (SPE) purification and formulation. The developed synthesis method reduced the amount of precursor and other chemicals required for synthesis compared to conventional radiosynthesizers. Conclusions: The microfluidic-based approach enabled the implementation of radiosynthesis of [68Ga]Ga-FAPI-46 and [68Ga]Ga-DOTA-TOC on the iMiDEV™ microfluidic module, paving the way for their use in preclinical and clinical applications. The microfluidic synthesis approach utilized 2–3 times less precursor than cassette-based conventional synthesis. The synthesis method was also successfully validated in a similar microfluidic iMiDEV module at a different research center for the synthesis of [68Ga]Ga-FAPI-46 with limited runs. Our study demonstrated the potential of microfluidic methods for efficient and reliable radiometal-based radiopharmaceutical synthesis, contributing valuable insights for future advancements in this field and paving the way for routine clinical applications in the near future. [ABSTRACT FROM AUTHOR]

The diagnosis and understanding of pain is challenging in clinical practice. Assessing pain relies heavily on self-reporting by patients, rendering it inherently subjective. Traditional clinical imaging methods such as computed tomography and magnetic resonance imaging can only detect anatomical abnormalities, offering limited sensitivity and specificity in identifying pain-causing conditions. Radiotracers play a vital role in molecular imaging that aims to identify abnormal biological processes at the cellular level, even in apparently normal anatomical structures. Therefore, molecular imaging is an important area of research as a prospective diagnostic modality for pain-causing pathophysiology. We present a mini review of the current knowledge base regarding radiotracers for identification of pain in vivo. We also describe radiocaine, a novel positron emission tomography imaging agent for sodium channels that has shown great potential for identifying/labeling pain-producing nerves and producing an objectively measurable pain intensity signal. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles (IONP) have been hailed as potential game-changers in biomedical imaging owing to their biocompatibility and size-dependent properties. One area where IONP has shown particular promise is magnetic resonance imaging (MRI), which traditionally uses superparamagnetic nanomaterials to produce negative contrast that darkens the tissues where nanoparticles accumulates. Unfortunately, this hypointense signal is a major drawback for clinical applications because it can make it difficult to identify the accumulated probes. As a result, researchers are exploring alternative options that can incorporate the advantages of IONP while also possessing valuable properties for molecular imaging. To achieve this goal, the most effective method involves not only utilizing positive contrast in MRI applications but also combining IONP with the unparalleled sensitivity of nuclear imaging techniques, for example, using radioisotopes to create PET/(T1)-MRI multimodal probes. To create such probes, various factors must be considered, including the radiolabeling strategy employed and overall complexity of the final nanoprobe. These nanoradiomaterials offer novel possibilities that span beyond the molecular imaging field, showing potential for the development of radiopharmaceuticals and theranostics. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor therapy targeting the PD-1/PD-L1 axis in cancer patients, is a promising oncological treatment. However, the number of non-responders remains high, causing a burden for the patient and the healthcare system. Consequently, a diagnostic tool to predict treatment outcomes would help with patient stratification. Molecular imaging provides said diagnostic tool by offering a whole-body quantitative assessment of PD-L1 expression, hence supporting therapy decisions. Four PD-L1 radioligand candidates containing a linker-chelator system for radiometalation, along with three hydrophilizing units—one sulfonic and two phosphonic acids—were synthesized. After labeling with 64Cu, log D7.4 values of less than −3.03 were determined and proteolytic stability confirmed over 94% intact compound after 48 h. Binding affinity was determined using two different assays, revealing high affinities up to 13 nM. µPET/CT imaging was performed in tumor-bearing mice to investigate PD-L1-specific tumor uptake and the pharmacokinetic profile of radioligands. These results yielded an unexpected in vivo distribution, such as low tumor uptake in PD-L1 positive tumors, high liver uptake, and accumulation in bone/bone marrow and potentially synovial spaces. These effects are likely caused by Ca2+-affinity and/or binding to macrophages. Despite phosphonic acids providing high water solubility, their incorporation must be carefully considered to avoid compromising the pharmacokinetic behavior of radioligands. [ABSTRACT FROM AUTHOR]

An optimized synthesis method for 6-[18F]fluoropiperonal (6-[18F]FP) via nucleophilic substitution of the nitro group in the precursor molecule (nitropiperonal, 6-NP) with [18F]fluoride in the presence of tetrabutylammonium tosylate has been proposed. Using this weakly basic phase transfer catalyst, the amount of initial 6-NP in the reaction was reduced from 4.0 to 0.2 mg with negligible amounts after subsequent treatment of the reaction mixture with a strong base (potassium methoxide). In turn, this made it possible to separate 6-[18F]FP and 6-NP with similar physicochemical properties by a simple and efficient solid-phase extraction technique on disposable cartridges. 6-[18F]FP was fabricated with 99% radiochemical purity and a radiochemical yield of 10%. The content of unreacted 6-NP did not exceed 1 µg/mL, which is comparable to the results of laborious semi-preparative HPLC purification. [ABSTRACT FROM AUTHOR]

This publication presents the application of radiotracers in the characterization of industrial flotation circuits. Two examples are showcased: the detection of feed flow rate imbalances and the characterization of particle size segregation in automatic mineral-cutting machines. The feed pulp distribution was determined from the mean residence times. Particle size segregation was measured by sampling the cutting machines (≅ 25 grams samples) using coarse, intermediate, and fine-sized radiotracer particles. Radiotracers were injected into the feed streams and measured at various points of the circuit using nuclear instruments, allowing for non-invasive and real time detection. Results show that in the rougher flotation stage, the feed flow is distributed almost evenly in lines 2 and 3 (approximately 38% of the flow goes to each line) and to a lesser extent towards line 4 (approximately 24%). In lines 1 and 2 of the scavenger stage, a higher percentage of the flow goes towards line 1 (approximately 59%) and a lower percentage towards line 2 (41%). Line 6 of the rougher flotation is the fastest of the circuit (shortest residence time). In addition, the inlet mineral-cutting machine of the rougher stage segregates particles with a bias for fine sizes (11.4 % more fine-sized particles than coarse ones). This work is an example of how radiotracer technology can be applied to improve metal production and processes. Radiotracers provide reliable information to be used in combination with other metallurgical data to properly assess flotation circuits. [ABSTRACT FROM AUTHOR]

PURPOSE: Many radiotracers are currently available for the detection of recurrent prostate cancer (rPC), yet many have not been compared head-to-head in comparative imaging studies. There is therefore an unmet need for evidence synthesis to guide evidence-based decisions in the selection of radiotracers. The objective of this study was therefore to assess the detection rate of various radiotracers for the rPC. METHODS: The PUBMED, EMBASE, and the EU and NIH trials databases were searched without date or language restriction for comparative imaging tracers for 13 radiotracers of principal interest. Key search terms included 18F-PSMA-1007, 18F-DCPFyl, 68Ga-PSMA-11, 18F-PSMA-11, 68Ga-PSMA-I&T, 68Ga-THP-PSMA, 64Cu-PSMA-617, 18F-JK-PSMA-7, 18F-Fluciclovine, 18F-FABC, 18F-Choline, 11C-Choline, and 68Ga-RM2. Studies reporting comparative imaging data in humans in rPC were selected. Single armed studies and matched pair analyses were excluded. Twelve studies with eight radiotracers were eligible for inclusion. Two independent reviewers screened all studies (using the PRISMA-NMA statement) for inclusion criteria, extracted data, and assessed risk of bias (using the QUADAS-2 tool). A network meta-analysis was performed using Markov-Chain Monte Carlo Bayesian analysis to obtain estimated detection rate odds ratios for each tracer combination. RESULTS: A majority of studies were judged to be at risk of publication bias. With the exception of 18F-PSMA-1007, little difference in terms of detection rate was revealed between the three most commonly used PSMA-radiotracers (68Ga-PSMA-11, 18F-PSMA-1007, 18F-DCFPyl), which in turn showed clear superiority to choline and fluciclovine using the derived network. CONCLUSION: Differences in patient-level detection rates were observed between PSMA- and choline-radiotracers. However, there is currently insufficient evidence to favour one of the four routinely used PSMA-radioligands (PSMA-11, PSMA-1007, PSMA-I&T, and DCFPyl) over another owing to the limited evidence base and risk of publication bias revealed by our systematic review. A further limitation was lack of reporting on diagnostic accuracy, which might favour radiotracers with low specificity in an analysis restricted only to detection rate. The NMA derived can be used to inform the design of future clinical trials and highlight areas where current evidence is weak.

Dementia is a significant global health issue that is exacerbated by an aging population. Imaging plays an established role in the evaluation of patients with neurocognitive disorders such as dementia. In current clinical practice, magnetic resonance imaging (MRI) and positron emission tomography (PET) are primary imaging modalities used separately but in concert to help diagnose and classify dementia. The clinical applications of PET/MRI hybrid imaging in dementia are an active area of research, particularly given the continued emergence of functional MRI (fMRI) and amyloid PET tracers. This narrative review provides a comprehensive overview of the rationale and current evidence for PET/MRI hybrid dementia imaging from 2018 to 2023. Hybrid imaging offers advantages in the accuracy of characterizing neurodegenerative disorders, and future research will need to address the cost of integrated PET/MRI systems compared to stand-alone scanners, the development of new biomarkers, and image correction techniques.

The differentiation of splenic tissue from malignant lesions via imaging may be challenging, particularly considering aberrant or accessory lesions and diseases that are rarely encountered. Functioning splenic tissue can be identified using technetium-99m red blood cell (99mTc-RBC) scintigraphy, but its sensitivity is limited and may not be available. We present the case of a patient in whom disseminated abdomino-pelvic splenosis was diagnosed using PET/CT with gallium-68-oxine-labeled RBCs. The method represents a feasible and probably superior alternative to splenic scintigraphy.

Waters recharging the subsurface contain a variety of naturally occurring geochemical components, the concentrations of which are principally a function of the atmosphere and surface environment. Over time, water-rock interactions and radiogenic processes in the subsurface control a complex geochemical evolution, impacting the initial surface-related signatures associated with recharged groundwaters. The rates of these geochemical changes are considerable in many important geologic settings, requiring characterisation and quantification of the dominant subsurface processes and evolving fluid characteristics. Constraining this is critically important for the discipline of fluid 'age' dating - hydrogeochronology. Age dating, or quantification of fluid residence times is typically evaluated through two categories of tracers; those that are incorporated at the point of recharge and decrease over time through radioactive decay (e.g. 3H, 14C, 81Kr) and those that increase over time (e.g. radiogenic noble gases) due to subsurface production and accumulation in fluids. As these fluids, elements, and tracers have different provenance, the calculated 'age' of any fluid represents the average, or mean residence time, of all components. Likewise, additional mechanisms of subsurface tracer production or loss can have significant bearing on any element-specific calculated residence times. The inevitable temporal discrepancies between tracers can be generated or accentuated in the subsurface which can prove difficult to reconcile in hydrogeochronologic modelling approaches. By incorporating geochemical data into existing neutron flux-based models, this study evaluates specifically how subsurface production of 'diminishing' tracers in the fluid phase, via neutron capture of parent elements, can produce complexity in the dating of host fluids. The in situ rates and production routes of 3H, 14C, 36Cl 39Ar, and 81Kr in different subsurface fluids are modelled for a variety of host rock lithologies to evaluate the effect such baseline crustal production in different geochemical settings may have on calculated residence times within naturally occurring systems. In particular this model provides a quantitative evaluation for how site-specific subsurface radiogeochemistry may result in enhanced baselines of 36Cl, 39Ar, (and potentially 14C) relative to canonical assumptions, and substantially impact residence time estimates calculated from these tracers for a range of subsurface environments. Additionally, we evaluate the role geologic environments can have on low levels of baseline production and calculated residence times for 3H and 81Kr. This study quantitatively evaluates the dependence of geologic environments on these subsurface processes and the impacts this may have on hydrogeochronologic studies. The ability to quantify production of tracers in the subsurface and recalibrate associated residence times in a wide range of geologic settings is of direct relevance to areas such as groundwater resource management, Carbon Capture and Storage, hydrogen storage and nuclear waste management strategies, the hydrocarbon and energy industry, and investigations of the timing and evolution of subsurface microbial life. [ABSTRACT FROM AUTHOR]

This review describes the basic principles of radiometal-theranostics and its dawn based on the development of the positron-emitting 86Y and 86Y-labeled radiopharmaceuticals to quantify biodistribution and dosimetry of 90Y-labeled analogue therapeutics. The nuclear and inorganic development of 86Y (including nuclear and cross section data, irradiation, radiochemical separation and recovery) led to preclinical and clinical evaluation of 86Y-labeled citrate and EDTMP complexes and yielded organ radiation doses in terms of mGy/MBq 90Y. The approach was extended to [86/90Y]Y-DOTA-TOC, yielding again yielded organ radiation doses in terms of mGy/MBq 90Y. The review further discusses the consequences of this early development in terms of further radiometals that were used (68Ga, 177Lu etc.), more chelators that were developed, new biological targets that were addressed (SSTR, PSMA, FAP, etc.) and subsequent generations of radiometal-theranostics that resulted out of that. [ABSTRACT FROM AUTHOR]

Organotrifluoroborates have gained acceptance as radioprosthetic groups for radiofluorination. Of these, the zwitterionic prosthetic group "AMBF3" with a quaternary dimethylammonium ion dominates the trifluoroborate space. Herein, we report on imidazolium‐methylene trifluoroborate (ImMBF3) as an alternative radioprosthetic group and report on its properties in the context of a PSMA‐targeting EUK ligand that was previously been conjugated to AMBF3. The ImMBF3 is readily synthesized from imidazole and conjugated via CuAAC "click" chemistry to give a structure similar to PSMA‐617. 18F‐labeling proceeded in one step per our previous reports and imaged in LNCaP‐xenograft bearing mice. The [18F]‐PSMA‐617‐ImMBF3 tracer proved to be less polar (LogP7.4 = −2.95 ± 0.03) while showing a significantly lower solvolytic rate (t1/2 = 8100 min) and slightly higher molar activity (Am) at 174 ± 38 GBq/μmol. Tumor uptake was measured at 13.7 ± 4.8%ID/g and a tumor:muscle ratio of 74.2 ± 35.0, tumor:blood ratio of 21.4 ± 7.0, tumor:kidney ratio of 0.29 ± 0.14, and tumor:bone ratio of 23.5 ± 9.5. In comparison with previously reported PSMA‐targeting EUK‐AMBF3 conjugates, we have altered the LogP7.4 value, tuned the solvolytic half‐life of the prosthetic, and increased radiochemical conversion while achieving similar tumor uptake, contrast ratios, and molar activities compared with AMBF3 bioconjugates. [ABSTRACT FROM AUTHOR]

The application of [18F]-fluorodeoxyglucose ([18F]FDG) as a radiotracer to detect sites of inflammation (either due to bacterial infection or primary inflammation) has led to exploring the role of PET in visualizing bacteria directly at sites of infection. However, the results from such efforts are controversial and inconclusive so far. We aimed to assess the limitations of PET as an effective modality in the diagnosis of bacterial infections. Inflammation due to bacterial infections can be visualized by using [18F]FDG-PET. However, the non-specificity of [18F]FDG makes it undesirable to visualize bacteria as the underlying cause of inflammation. Hence, more specific radiotracers that possibly bind to or accumulate in bacteria-specific receptors or enzymes are being explored. Several radiotracers, including 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS), 6-[18F]-fluoromaltose, [11C]para-aminobenzoic acid ([11C]PABA), radiolabeled trimethoprim (11C-TMP) and its analog fluoropropyl-trimethoprim (18F-FPTMP), other radiolabeled sugars, and antimicrobial drugs have been used to image microorganisms. Unfortunately, no progress has been made in translating the results to routine human use; feasibility and other factors have constrained their success in clinical settings. In the current article, we discuss the limitations of direct bacterial visualization with PET tracers, but emphasize the important role of [18F]FDG-PET as the only option for detecting evidence of infection. [ABSTRACT FROM AUTHOR]

Alessio Smeraldo,1– 3,&ast; Alfonso Maria Ponsiglione,1,&ast; Andrea Soricelli,4 Paolo Antonio Netti,1– 3 Enza Torino1– 3 1Department of Chemical, Materials and Production Engineering, University of Naples “Federico II”, Naples, 80125, Italy; 2Interdisciplinary Research Center on Biomaterials, CRIB, Naples, 80125, Italy; 3Center for Advanced Biomaterials for Health Care, CABHC, Istituto Italiano di Tecnologia, IIT@CRIB, Naples, 80125, Italy; 4Department of Motor Sciences and Healthiness, University of Naples “Parthenope”, Naples, 80133, Italy&ast;These authors contributed equally to this workCorrespondence: Enza Torino, Department of Chemical, Materials and Production Engineering, University of Naples “Federico II”, Piazzale Tecchio 80, Naples, 80125, Italy, Tel +39-328-955-8158, Email enza.torino@unina.itAbstract: The recent advancements in hybrid positron emission tomography–magnetic resonance imaging systems (PET/MRI) have brought massive value in the investigation of disease processes, in the development of novel treatments, in the monitoring of both therapy response and disease progression, and, not least, in the introduction of new multidisciplinary molecular imaging approaches. While offering potential advantages over PET/CT, the hybrid PET/MRI proved to improve both the image quality and lesion detectability. In particular, it showed to be an effective tool for the study of metabolic information about lesions and pathological conditions affecting the brain, from a better tumor characterization to the analysis of metabolic brain networks. Based on the PRISMA guidelines, this work presents a systematic review on PET/MRI in basic research and clinical differential diagnosis on brain oncology and neurodegenerative disorders. The analysis includes literature works and clinical case studies, with a specific focus on the use of PET tracers and MRI contrast agents, which are usually employed to perform hybrid PET/MRI studies of brain tumors. A systematic literature search for original diagnostic studies is performed using PubMed/MEDLINE, Scopus and Web of Science. Patients, study, and imaging characteristics were extracted from the selected articles. The analysis included acquired data pooling, heterogeneity testing, sensitivity analyses, used tracers, and reported patient outcomes. Our analysis shows that, while PET/MRI for the brain is a promising diagnostic method for early diagnosis, staging and recurrence in patients with brain diseases, a better definition of the role of tracers and imaging agents in both clinical and preclinical hybrid PET/MRI applications is needed and further efforts should be devoted to the standardization of the contrast imaging protocols, also considering the emerging agents and multimodal probes.Keywords: PET/MRI, contrast agents, radiotracers, brain oncology, medical imaging

Early applications of positron emission tomography (PET) in psychiatry sought to identify derangements of cerebral blood flow and metabolism. The need for more specific neurochemical imaging probes was soon evident, and these probes initially targeted the sites of action of neuroleptic (dopamine D2 receptors) and psychoactive (serotonin receptors) drugs. For nearly 30 years, the centrality of monoamine dysfunction in psychiatric disorders drove the development of an armamentarium of monoaminergic PET radiopharmaceuticals and imaging methodologies. However, continued investments in monoamine‐enhancing drug development realized only modest gains in efficacy and tolerability. As patent protection for many widely prescribed and profitable psychiatric drugs lapsed, drug development pipelines shifted away from monoamines in search of novel targets with the promises of improved efficacy, or abandoned altogether. Over this period, PET radiopharmaceutical development activities closely parallelled drug development priorities, resulting in the development of new PET imaging agents for non‐monoamine targets. In part two of this review, we survey clinical research studies using the novel targets and radiotracers described in part one across major psychiatric application areas such as substance use disorders, anxiety disorders, eating disorders, personality disorders, mood disorders, and schizophrenia. Important limitations of the studies described are discussed, as well as key methodologic issues, challenges to the field, and the status of clinical trials seeking to exploit these targets for novel therapeutics. [ABSTRACT FROM AUTHOR]

With the emergence of positron emission tomography (PET) in the late 1970s, psychiatry had access to a tool capable of non‐invasive assessment of human brain function. Early applications in psychiatry focused on identifying characteristic brain blood flow and metabolic derangements using radiotracers such as [15O]H2O and [18F]FDG. Despite the success of these techniques, it became apparent that more specific probes were needed to understand the neurochemical bases of psychiatric disorders. The first neurochemical PET imaging probes targeted sites of action of neuroleptic (dopamine D2 receptors) and psychoactive (serotonin receptors) drugs. Based on the centrality of monoamine dysfunction in psychiatric disorders and the measured success of monoamine‐enhancing drugs in treating them, the next 30 years witnessed the development of an armamentarium of PET radiopharmaceuticals and imaging methodologies for studying monoamines. Continued development of monoamine‐enhancing drugs over this time however was less successful, realizing only modest gains in efficacy and tolerability. As patent protection for many widely prescribed and profitable psychiatric drugs lapsed, drug development pipelines shifted away from monoamines in search of novel targets with the promises of improved efficacy, or abandoned altogether. Over this period, PET radiopharmaceutical development activities closely paralleled drug development priorities resulting in the development of new PET imaging agents for non‐monoamine targets. Part one of this review will briefly survey novel PET imaging targets with relevance to the field of psychiatry, which include the metabotropic glutamate receptor type 5 (mGluR5), purinergic P2X7 receptor, type 1 cannabinoid receptor (CB1), phosphodiesterase 10A (PDE10A), and describe radiotracers developed for these and other targets that have matured to human subject investigations. Current limitations of the targets and techniques will also be discussed. [ABSTRACT FROM AUTHOR]

This research aims to explore the chromium removal from water using copper-based nanoparticles. The nanoparticles were synthesized by hydrothermal method and characterized by X-ray diffraction, scanning electron microscopy, infrared spectroscopy, and X-ray photoelectron spectroscopy as well as determination of the specific surface area (SBET) and point of zero charge (PZC). The size and composition of nanoparticles are influenced by the reaction time, organic coating, and oxidizing atmosphere. Sorption experiments were carried out in aqueous solutions as well as simulated drinking water at various initial concentration, time, and temperature. Cu nanoparticles had a significant Cr uptake capacity of 3.4 mg·g−1 for Cin 1.0 mg·L−1 lowering the Cr concentration below the provisional guideline value of 50 μg·L−1. Sorption isotherms were fitted to Henry, Langmuir, and Freundlich models, whereas kinetic data were reproduced by different kinetic models. Iodide sorption experiments were carried out to explore the sorption mechanism onto Cu-NPs. Considering the biocompatibility, stability, good uptake capacity, and reusability, Cu nanoparticles could be considered as promising agents for applications in water purification. [ABSTRACT FROM AUTHOR]

Atmospheric radioxenon analyses conducted under the Comprehensive Test Ban Treaty Organization (CTBTO) necessitates the collection of air samples to quantify 135Xe, an indicator for nuclear explosions and reactor operations. Analytical instrument calibration for these analyses requires high quality, monoisotopic reference standards that are typically short lived, and therefore must be produced and shipped promptly to monitoring stations worldwide. The work described here outlines two methods to produce highly enriched 135Xe by irradiating stable monoisotopic targets by (1) neutron capture (n, ɣ) on monoisotopic 134Xe and (2) high energy photon irradiation (ɣ, n) of monoisotopic 136Xe. The targets were prepared by electromagnetic isotope separation of natural xenon. Results from each process were compared for 135Xe yield and purity. [ABSTRACT FROM AUTHOR]

The differentiation of splenic tissue from malignant lesions via imaging may be challenging, particularly considering aberrant or accessory lesions and diseases that are rarely encountered. Functioning splenic tissue can be identified using technetium-99m red blood cell (99mTc-RBC) scintigraphy, but its sensitivity is limited and may not be available. We present the case of a patient in whom disseminated abdomino-pelvic splenosis was diagnosed using PET/CT with gallium-68-oxine-labeled RBCs. The method represents a feasible and probably superior alternative to splenic scintigraphy. [ABSTRACT FROM AUTHOR]

A key focus of cardiovascular medicine is the detection, treatment, and prevention of disease, with a move towards more personalized and patient-centred treatments. To achieve this goal, novel imaging approaches that allow for early and accurate detection of disease and risk stratification are needed. At present, the diagnosis, monitoring, and prognostication of thrombotic cardiovascular diseases are based on imaging techniques that measure changes in structural anatomy and biological function. Molecular imaging is emerging as a new tool for the non-invasive detection of biological processes, such as thrombosis, that can improve identification of these events above and beyond current imaging modalities. At the forefront of these evolving techniques is the use of high-sensitivity radiotracers in conjunction with positron emission tomography imaging that could revolutionise current diagnostic paradigms by improving our understanding of the role and origin of thrombosis in a range of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor therapy targeting the PD-1/PD-L1 axis in cancer patients, is a promising oncological treatment. However, the number of non-responders remains high, causing a burden for the patient and the healthcare system. Consequently, a diagnostic tool to predict treatment outcomes would help with patient stratification. Molecular imaging provides said diagnostic tool by offering a whole-body quantitative assessment of PD-L1 expression, hence supporting therapy decisions. Four PD-L1 radioligand candidates containing a linker-chelator system for radiometalation, along with three hydrophilizing units—one sulfonic and two phosphonic acids—were synthesized. After labeling with 64Cu, log D7.4 values of less than −3.03 were determined and proteolytic stability confirmed over 94% intact compound after 48 h. Binding affinity was determined using two different assays, revealing high affinities up to 13 nM. µPET/CT imaging was performed in tumor-bearing mice to investigate PD-L1-specific tumor uptake and the pharmacokinetic profile of radioligands. These results yielded an unexpected in vivo distribution, such as low tumor uptake in PD-L1 positive tumors, high liver uptake, and accumulation in bone/bone marrow and potentially synovial spaces. These effects are likely caused by Ca2+-affinity and/or binding to macrophages. Despite phosphonic acids providing high water solubility, their incorporation must be carefully considered to avoid compromising the pharmacokinetic behavior of radioligands.

Radioisotope applications in industrial process inspection and evaluation using gamma-ray emitters provide otherwise unavailable information. Offering alternative gamma-ray sources can support the technology by complementing sources’ availability and radiation safety. This work proposes to replace gamma-ray from radioisotopes with prompt gamma-ray from the interaction of neutrons with stable isotopes injected into the industrial process or with the structural material of the industrial process equipment. Monte Carlo N-Particle Transport Code (MCNP5) was used to simulate the irradiation of two-phase flow pipes by 252Cf neutron source. Two simulations were run for each pipe, with and without mixing the liquid phase with the stable isotope 157Gd. The detected gamma-ray spectra were analysed, and images of the two phases inside the pipes were produced. The images were compared to images obtained from simulations of gamma transmission measurement using 60Co. Furthermore, results for prompt gamma computed tomography (CT) were presented and discussed. The studies’ outcomes indicate the potential of prompt gamma-ray to carry out the sealed sources applications of gamma transmission measurements and imaging.

In cardiotoxicity, PET/MR affords an accurate evaluation of cardiovascular morphology, function, and also multi-parametric tissue characterization. A composite of several cardiac imaging parameters provided by the PET/MR scanner is likely to outperform a single parameter or imaging modality in the assessment and prediction of the severity and progression of cardiotoxicity but needing clinical investigations. Of particular interest, a heterogeneity map of single PET and CMR parameters could be perfectly correlated with the PET/MR scanner likely emerging as a promising marker of cardiotoxicity to monitor treatment response. While such functional and structural multiparametric imaging approach with cardiac PET/MR in the assessment and characterization of cardiotoxicity holds much promise, its validity and value in cancer patients treated with chemotherapy and/or radiation still needs to be assessed. The multi-parametric imaging approach with PET/MR, however, is likely to set new standards to develop predictive constellations of parameters for the severity and potential progression of cardiotoxicity that should afford timely and individualized treatment intervention to ascertain myocardial recovery and improved clinical outcome in these high-risk patients. • In cardiotoxicity, PET/MR affords an accurate evaluation of cardiovascular morphology, function, and also multi-parametric tissue characterization • A composite of several cardiac imaging parameters provided by the PET/MR scanner is likely to outperform a single parameter or imaging modality in the assessment and prediction of the severity and progression of cardiotoxicity but needing clinical investigations • Heterogeneity map of single PET and CMR parameters could be perfectly correlated with the PET/MR scanner likely emerging as a promising marker of cardiotoxicity to monitor treatment response [ABSTRACT FROM AUTHOR]

The excellent features of non‐invasive molecular imaging, its progressive technology (real‐time, whole‐body imaging and quantification), and global impact by a growing infrastructure for positron emission tomography (PET) scanners are encouraging prospects to investigate new concepts, which could transform clinical care of complex infectious diseases. Researchers are aiming towards the extension beyond the routinely available radiopharmaceuticals and are looking for more effective tools that interact directly with causative pathogens. We reviewed and critically evaluated (challenges or pitfalls) antibiotic‐derived PET radiopharmaceutical development efforts aimed at infection imaging. We considered both radiotracer development for infection imaging and radio‐antibiotic PET imaging supplementing other tools for pharmacologic drug characterization; overall, a total of 20 original PET radiotracers derived from eleven approved antibiotics. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic widespread cardiovascular disease and a major predisposing factor for cardiovascular events, among which there are myocardial infarction and ischemic stroke. Atherosclerotic plaque formation is a process that involves different mechanisms, of which inflammation is the most common. Plenty of radiopharmaceuticals were developed to elucidate the process of plaque formation at different stages, some of which were highly specific for atherosclerotic plaque. This review summarizes the current nuclear medicine imaging landscape of preclinical and small-scale clinical studies of these specific RPs, which are not as widespread as labeled FDG, sodium fluoride, and choline. These include oxidation-specific epitope imaging, macrophage, and other cell receptors visualization, neoangiogenesis, and macrophage death imaging. It is shown that specific radiopharmaceuticals have strength in pathophysiologically sound imaging of the atherosclerotic plaques at different stages, but this also may induce problems with the signal registration for low-volume plaques in the vascular wall. [ABSTRACT FROM AUTHOR]