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Objective(s): Despite recent advances in treatment modalities, cancer remains a major source of morbidity and mortality throughout the world. Currently, the development of sensitive and specific molecular imaging probes for early diagnosis of cancer is still a problematic challenge. Previous studies have been shown that some of the antimicrobial peptides (AMPs) exhibit a broad spectrum of cytotoxic activity against cancerous cells in addition to their antimicrobial activities. MicrocinJ25 (MccJ25) is an antimicrobial peptide that is produced by Escherichia coli (E. coli) strain. The aim of this study was to investigate the potential of a new peptide radiopharmaceutical derived from MccJ25 for diagnosis of melanoma tumor bearing C57BL/6 mice. Methods: A 14 amino acid analog of MccJ25 was labeled with technetium-99m (99mTc) through hydrazinonicotinamide (HYNIC) chelator and tricine as coligand. In vivo tumor uptake and tissue distribution were evaluated. The in vivo biodistribution studies were determined in C57BL/6 mice bearing B16F10 tumor. Results: The amount of non-peptide related 99mTc-impurities that measured by thin layer chromatography (TLC) did not exceed 5% of the total radioactivity. The in vitro binding to B16F10 cells was 30.73 ± 0.9% after 1 h incubation at 37°C, and saturation binding experiments showed good affinity for radio-complex (Kd=47.98±6.25 nM). The melanoma tumor was clearly visible up 1 h post-injection by gamma camera imaging. Conclusion: The results showed that 99mTc-labeld peptide could be a promising candidate as a targeting radiopharmaceutical for melanoma tumor imaging in mice.

Objective(s): Lymph node metastases are the most significant prognostic factor in localized non-small cell lung cancer (NSCLC). Identification of the first nodal drainage site (sentinel node) may improve detection of metastatic nodes. Extended surgeries, such as lobectomy or pneumonectomy with lymph node dissection, are among the therapeutic options of higher acceptability. Sentinel node biopsy can be an alternative approach to less invasive surgeries. The current study was conducted to evaluate the accuracy of sentinel node mapping in patients with NSCLC using an intraoperative radiotracer techniques. Methods: This prospective study was conducted on 21 patients with biopsy-proven NSCLC who were candidates for sentinel node mapping during 2012-2014. All patients underwent thoracoabdominal computed tomography, based on which they had no lymph node involvement. Immediately after thoracotomy and before mobilizing the tumor, peritumoral injection of 2mCi/0.4 mL Tc-99m- phytate was performed in 4 corners of tumor. After mobilization of the tumoral tissues, the sentinel nodes were searched for in the hillar and mediastinal areas using hand-held gamma probe . Any lymph node with in vivo count twice the background was considered as sentinel node and removed and sent for frozen section evaluation. All dissected nodes were evaluated by step sectioning and hematoxylin and eosin staining (H&E).The recorded data included age, gender, kind of pathology, site of lesion, number of dissected sentinel nodes, number of sentinel nodes, and site of sentinel nodes. Data analysis was performed in SPSS software (version 22). Results: The mean age of the patients was 58.52±11.46 years with a male to female ratio of 15/6. The left lower lobe was the most commonly affected site (30.09%). Squamous cell carcinoma and adenocarcinoma were detected in 11 and 10 subjects, respectively. A total of 120 lymph nodes were harvested with the mean number of 5.71±2.9 lymph nodes per patient. At least one sentinel node was identified in each patient, resulting in a detection rate of 95.2%. The mean number of sentinel nodes per patient was 3.61±2. Frozen section results showed 100% concordance with the results of hematoxylin and eosin staining. Conclusion: Based on the findings, sentinel node mapping can be considered feasible and accurate for lymph node staging and NSCLC treatment.

Abstract Purpose We have previously developed the caspase-based radiotracer, 18F-ICMT-11, for PET imaging to monitor treatment response. We further validated 18F-ICMT-11 specificity in a murine melanoma death-switch tumour model with conditional activation of caspase-3 induced by doxycycline. Methods Caspase-3/7 activity and cellular uptake of 18F-ICMT-11, 18F-ML-10 and 18F-FDG were assessed in B16ova and B16ovaRevC3 cells after death-switch induction. Death-switch induction was confirmed in vivo in xenograft tumours, and 18F-ICMT-11 and 18F-ML-10 biodistribution was assessed by ex vivo gamma counting of select tissues. PET imaging was performed with 18F-ICMT-11, 18F-ML-10 and 18F-FDG. Caspase-3 activation was confirmed by immunohistochemistry. Results Significantly increased caspase-3/7 activity was observed only in B16ovaRevC3 cells after death-switch induction, accompanied by significantly increased 18F-ICMT-11 (p

Molecular imaging probes enable the early and accurate detection of disease-specific biomarkers and facilitate personalized treatment of many chronic diseases, including cancer. Among current clinically used functional imaging modalities, positron emission tomography (PET) plays a significant role in cancer detection and in monitoring the response to therapeutic interventions. Several preclinical and clinical studies have demonstrated the crucial involvement of cyclooxygenase-2 (COX-2) isozyme in cancer development and progression, making COX-2 a promising cancer biomarker. A variety of COX-2-targeting PET radioligands has been developed based on anti-inflammatory drugs and selective COX-2 inhibitors. However, many of those suffer from non-specific binding and insufficient metabolic stability. This article highlights examples of COX-2-targeting PET radioligands labelled with the short-lived positron emitter 18F, including radiosynthesis and PET imaging studies published in the last decade (2012–2021).

This review lists the most important radiotracers described so far for imaging the central serotoninergic system. Single-photon emission computed tomography and positron emission tomography radiotracers are reviewed and critically discussed for each receptor.

The use of radiotracers in the present study is intended to replace traditional steps of metal quantitative analysis (solution sampling and instrumental chemical analysis) and to allow real-time measurements of metal concentrations during the leaching process. In this study, 64Cu, an isotope of copper, was selected as a radiotracer. Samples of copper flotation tailings were irradiated in the Maria research reactor (Świerk, Poland) and mixed with an inactive portion of the milled fl otation waste. The leaching process was carried out in a glass reactor, and the radiation spectrum was measured using a gamma spectrometer. The material was then treated using various acids (sulphuric acid, nitric acid, acetic acid, citric acid, and ascorbic acid) in a wide range of their concentrations. Experiments with the radiotracer were conducted in sulphuric and nitric acids. The amount of the leached metal (copper) was calculated on the basis of the peak area ratio in the gamma-ray spectrum of the activated tailings and standard samples. Inductively coupled plasma mass spectrometry (ICP-MS) was also used to analyse the metal content. Maximum recovery of 56% Cu was achieved using 9 M HNO3, whereas the recovery was lowest for ascorbic acid (

Abstract Objectives In vivo evaluations of a gonadotropin releasing hormone-receptor single photon emission computed tomography radiotracer for non-invasive detection of gonadotropin releasing homone-receptors in brain. Results We have used a simple, robust and high-yielding procedure to radiolabel an alpha-halogenated bioactive compound with high radiochemical yield. Literature findings showed similar alpha-halogenated compounds suitable for in vivo evaluations. The compound was found to possess nano molar affinity for the gonadotropin releasing hormone-receptor in a competition dependent inhibition study. Furthermore, liquid chromatography-mass spectrometry analysis in saline, human and rat serum resulted in 46%, 52% and 44% stability after incubation for 1 h respectively. In addition, rat brain single photon emission computed tomography and biodistribution studies gave further insight into the nature of the compound as a radiotracer.

Aim: Here, we established a reliable strategy for generation and characterization of targeted radiolabeled exosomes for the detection of HER2-positive cells quantitatively. Materials & methods: Targeted exosomes (T-exos) were radiolabeled by two different radiotracers, [99mTc]Tc-HMPAO or [111In]In-oxine. The labeling efficiency and stability were assessed using exosome exclusive spin columns. HER2-positive and -negative cells were treated with [111In]In-oxine-exosomes after 3 and 24 h. Results: [111In]In-oxine labeling did not change the binding ability and general features of the exosomes. With [111In]In-oxine, 70% labeling efficiency and 78% radiochemical stability over 24 h were achieved. [111In]In-oxine-T-exos showed greater uptake by HER2-positive cells compared with untargeted exosomes. Conclusion: [111In]In-oxine-T-exos could potentially be used as an effective imaging tool for HER2 expression. [ABSTRACT FROM AUTHOR]

Background Amino acid PET imaging of brain tumors has been shown to play an important role in predicting tumor grade, delineation of tumor margins, and differentiating tumor recurrence from the background of postradiation changes, but is not commonly used in clinical practice because of high cost. We propose that PET/MRI imaging of patients grouped to the day of tracer radiosynthesis will significantly decrease the cost of PET imaging, which will improve patient access to PET. Methods Seventeen patients with either primary brain tumors or metastatic brain tumors were recruited for imaging on 3T PET/MRI and were scanned on 4 separate days in groups of 3 to 5 patients. The first group of consecutively imaged patients contained 3 patients, followed by 2 groups of 5 patients, and a last group of 4 patients. Results For each of the patients, standard of care gadolinium-enhanced MRI and dynamic PET imaging with 18F-FDOPA amino acid tracer was obtained. The total cost savings of scanning 17 patients in batches of 4 as opposed to individual radiosynthesis was 48.5% ($28 321). Semiquantitative analysis of tracer uptake in normal brain were performed with appropriate accumulation and expected subsequent washout. Conclusion Amino acid PET tracers have been shown to play a critical role in the characterization of brain tumors but their adaptation to clinical practice has been limited because of the high cost of PET. Scheduling patient imaging to maximally use the radiosynthesis of imaging tracer significantly reduces the cost of PET and results in increased availability of PET tracer use in neuro-oncology. [ABSTRACT FROM AUTHOR]

Discovery of 99mTc-labeled imidazole derivatives as a potential radiotracer for hypoxic tumor imaging is considered to be of great interest because of non-invasive detection capabilities. 2-Mercaptobenzimidazole (2-MBI) was successfully synthesized, characterized and radiolabeled with [99mTc (CO)3(H2O)3]+ intermediate to form 99mTc-2-MBI complex with radiochemical purity of ≥95% yield as observed by instant-thin layer chromatography (ITLC) and radio-high performance liquid chromatography (radio-HPLC). The 99mTc-2-MBI complex was observed to be stable in saline and serum with no noticeable decomposition at room temperature and 37 °C, respectively, over a time period of 24 h. Biodistribution results in Balb/c mice bearing S180 tumor show that 99mTc-2-MBI highly internalized in tumor tissue, also possess preferably high tumor/muscle and tumor/blood ratios 4.14 ± 0.77 and 3.91 ± 0.63, respectively at 24 h incubation. Scintigraphic imaging study shows 99mTc-2-MBI is visibly accumulated in hypoxic tumor tissue, suggesting it would be a promising radiotracer for early stage diagnosis of tumor hypoxia.

Legumes associate with root colonizing rhizobia that provide fixed nitrogen to its plant host in exchange for recently fixed carbon. There is a lack of understanding of how individual plants modulate carbon allocation to a nodulated root system as a dynamic response to abiotic stimuli. One reason is that most approaches are based on destructive sampling, making quantification of localised carbon allocation dynamics in the root system difficult. We established an experimental workflow for routinely using non-invasive Positron Emission Tomography (PET) to follow the allocation of leaf-supplied 11C tracer towards individual nodules in a three-dimensional (3D) root system of pea (Pisum sativum). Nitrate was used for triggering a reduction of biological nitrogen fixation (BNF), which was expected to rapidly affect carbon allocation dynamics in the root-nodule system. The nitrate treatment led to a decrease in 11C tracer allocation to nodules by 40% to 47% in 5 treated plants while the variation in control plants was less than 11%. The established experimental pipeline enabled for the first time that several plants could consistently be labelled and measured using 11C tracers in a PET approach to quantify C-allocation to individual nodules following a BNF reduction. Our study demonstrates the strength of using 11C tracers in a PET approach for non-invasive quantification of dynamic carbon allocation in several growing plants over several days. A major advantage of the approach is the possibility to investigate carbon dynamics in small regions of interest in a 3D system such as nodules in comparison to whole plant development.

In the past two decades, the radioactive particle tracking (RPT) measurement technique has been proven to visualize flow fields of most multiphase flow systems of industrial interest. The accuracy of RPT, and hence the data obtained, depend largely on the calibration process, which stands here as a basis for two subsequent processes: tracking and reconstruction. However, limitations in the RPT calibration process can be found in different experimental constrains and in assumptions made in the classical Monte Carlo approach used to simulate number of counts received by the detectors. Therefore, in this work, we applied a GEANT4-based Monte Carlo code to simulate the RPT calibration process for an investigated multiphase flow system (i.e., gas–liquid bubble column). The GEANT4 code was performed to simulate the number of counts received by 28 scintillation detectors for 931 known tracer positions while capturing all the types of photon interaction and overcoming solids’ angle limitations in classical approaches. The results of the simulation were validated against experimental data obtained using an automated RPT calibration device. The results showed a good agreement between the simulated and experimental counts, where the maximum absolute average relative deviation detected was about 5%. The GEANT4 model typically predicted the number of counts received by all the detectors; however, it over-estimated the counts when the number of primary events applied in the model was not the optimal.

The membrane-bound transport proteins responsible for oxalate secretion across the large intestine remain unidentified. The apical chloride/bicarbonate (Cl−/HCO3−) exchanger encoded by Slc26a6, known as PAT-1 (putative anion transporter 1), is a potential candidate. In the small intestine, PAT-1 makes a major contribution to oxalate secretion but whether this role extends into the large intestine has not been directly tested. Using the PAT-1 knockout (KO) mouse, we compared the unidirectional absorptive ( J ms ion ) and secretory ( J sm ion ) flux of oxalate and Cl− across cecum, proximal colon, and distal colon from wild-type (WT) and KO mice in vitro. We also utilized the non-specific inhibitor DIDS (4,4′-diisothiocyano-2,2′-stilbenedisulfonic acid) to confirm a role for PAT-1 in WT large intestine and (in KO tissues) highlight any other apical anion exchangers involved. Under symmetrical, short-circuit conditions the cecum and proximal colon did not transport oxalate on a net basis, whereas the distal colon supported net secretion. We found no evidence for the participation of PAT-1, or indeed any other DIDS-sensitive transport mechanism, in oxalate or Cl− by the large intestine. Most unexpectedly, mucosal DIDS concurrently stimulated J ms Ox and J sm Ox by 25–68% across each segment without impacting net transport. For the colon, these changes were directly proportional to increased transepithelial conductance suggesting this response was the result of bidirectional paracellular flux. In conclusion, PAT-1 does not contribute to oxalate or Cl− transport by the large intestine, and we urge caution when using DIDS with mouse colonic epithelium. [ABSTRACT FROM AUTHOR]

The highly bidirectional dialogue between the gut and the brain is markedly stimulated and influenced by the microbiome through integrated neuroendocrine, neurological and immunological processes. Gut microbiota itself communicate with the host producing hormonal intermediates, metabolites, proteins, and toxins responsible for a variety of biochemical and functional inputs, thereby shaping host homeostasis. Indeed, a dysregulated microbiota-gut-brain axis might be the origin of many neuroimmune-mediated disorders, e.g. autism, multiple sclerosis, depression, Alzheimer's and Parkinson's disease, which appear months or even years prior to a diagnosis, corroborating the theory that the pathological process is spread from the gut to the brain. A much deeper comprehension of how commensal microbe can be manipulated to interfere with disease progression is crucial for developing new strategies to diagnose and treat diseases. In recent years, the potential of positron-emission-tomography (PET) in the field of bacteria detection has gained attention. The uptake of several PET tracers has been evaluated to investigate infection pathophysiology, e.g. sterile or pathogen-mediated infection, monitoring of progression, or as a surrogate endpoint in clinical trials. In this minireview, we briefly describe the role of microbiome-gut-brain axis in health and disease and we discuss the imaging modalities and agents that could be applied to study the dynamic interactions between microbiome, gut and brain. These are key aspects in understanding the biochemical lexicon underpinning the microbiome-host crosstalk that would enable the development of diagnostics and therapeutics by targeting the human microbiota. [ABSTRACT FROM AUTHOR]

Enhancer of zeste homolog 2 (EZH2) is responsible for the methylation of lysine 27 of histone H3 (H3K27) leading to transcriptional repression. Consequently, EZH2 is related with several diseases including cancers, as overexpressed EZH2 can down-regulate cancer suppressor genes. Therefore, EZH2 became a promising target for cancer treatment and diagnosis and in vivo imaging of EZH2 is critical for diagnosis and treatment monitor. In the present work, we radiolabeled a specific inhibitor of EZH2, [11C]EI1, investigated its pharmacokinetics and performed micro PET/CT imaging. Results showed that the half-life of the [11C]EI1 in blood was 3.4 min. Micro PET/CT imaging showed that the [11C]EI1 can enter the major organs including liver, stomach, and intestine and can be blocked by the unlabeled EI1 resulting in a significant distinct between apparent distribution volumes (Vd, 2.8 mL for blocking versus 17.4 ml for baseline), which validated the specific affinity of the [11C]EI1 against EZH2 and illustrated the distribution of EZH2 in major organs. The results indicated that the [11C]EI1 can be a tracer for EZH2 PET imaging used in diagnosis and therapy monitor of EZH2 related diseases especially cancers. [ABSTRACT FROM AUTHOR]

Objective: Genistein is an isoflavone compound that has been proven to have anticancer activity and is capable of binding to estrogen β receptors with Selective Estrogen Receptor Modulators (SERMs) properties, and has a strong affinity to inhibit the development of cancer cells. This study is to determine the optimum conditions of the reaction in the synthesis process of compounds labeled 131I-genestein which can be potential for application of breast cancer diagnosis. Methods: Synthesis of 131I-Genistein compound labeling using the Chloramine-T iodination method. This method uses several parameter optimizations, including: pH conditions, the amount of chloramine-T oxidizer and sodium metabisulfite reducing agent. The radiochemical purity of the 131I-Genistein compound was determined using thin layer chromatography TLC-SG F254, and measured by SCA (Single Channel Analyzer). The radiochemical purity of labeled compounds must fulfill the requirements of the United States of Pharmacopeia. Results: Optimization of the synthesis conditions of the 131I-Genistein compound was obtained at pH 8, the amount of chloramine-T 0.225 mg, and the amount of Na-Metabisulfite 0.342 mg, with 30 min reaction time. This optimum condition produces radiochemical purity of 95.02 ± 0.76%. Conclusion: Products labeled 131I-Genistein meet radiochemical purity requirements according to USP requirements. The labeled compound is expected to be able to be used to detect breast cancer through a binding mechanism with estrogen receptors β.

Radiolabeling cidofovir with technetium-99m (99mTc-CDV) is an innovative procedure that enables real-time monitoring of the drug. Essays were performed in vitro, showing high radiolabel stability within 24 h. Blood clearance, biodistribution studies, and scintigraphic images were performed in healthy mice in order to evaluate the profile of the drug in vivo. 99mTc-CDV showed biphasic blood circulation time and significant kidney uptake, indicating that 99mTc-CDV is preferentially eliminated by the renal route. Bones also showed important uptake throughout the experiment. In summary, cidofovir was successfully labeled with technetium-99m and might be used in further studies to track the drug.

Bromodomain and extra-terminal domain (BET) family proteins have become a hot research area because of their close relationship with a variety of human diseases. The non-invasive imaging technique, such as positron emission tomography (PET), provides a powerful tool to visualize and quantify the BET family proteins that accelerating the investigation of this domain. Herein, we describe the development of a promising PET probe, [11C]1, specifically targeting BET family proteins based on the potent BET inhibitor CF53. [11C]1 was successfully radio-synthesized with good yield and high purity after the optimization of radiolabeling conditions. The in vivo bio-activities evaluation of [11C]1 was performed using PET imaging in rodents. The results demonstrated that [11C]1 has favorable uptake in peripheral organs and moderate uptake in the brain. Further blocking studies indicated the high binding specificity and selectivity for BET proteins of this probe. Our findings suggest that [11C]1 is a promising BET PET probe for BET proteins as well as epigenetic imaging.

High-affinity monoamine transporters are targets for prescribed medications and stimulant drugs of abuse. Therefore, assessing monoamine transporter activity for candidate medications and newly-emerging drugs of abuse provides essential information for industry, academia, and public health. Radiotracer binding and uptake inhibition are the gold standard assays for determining drug–transporter interaction profiles. The combined results from such assays yield a unique biochemical fingerprint for each compound. Over time, different assay methods have been developed to assess transporter activity, and the comparability of data across various assay platforms remains largely unclear. Here, we compare the effects of six well-established stimulants in two different cell-based uptake inhibition assays, one method using adherent cells and the other using suspended cells. Furthermore, we compare the data from transfected cell lines derived from different laboratories and data reported from rat synaptosomes. For transporter inhibitors, IC50 values obtained by the two experimental methods were comparable, but using different transfected cell lines yielded disparate results. For transporter substrates, differences between the two cell lines were less pronounced but the drugs displayed different inhibition potencies when evaluated by the two methods. Our study illustrates the inherent limitations when comparing transporter inhibition data from different laboratories and stresses the importance of including appropriate control experiments with reference compounds when investigating new drugs of interest.

The flux of methane, a potent greenhouse gas, from the seabed is largely controlled by anaerobic oxidation of methane (AOM) coupled to sulfate reduction (S-AOM) in the sulfate methane transition (SMT). S-AOM is estimated to oxidize 90% of the methane produced in marine sediments and is mediated by a consortium of anaerobic methanotrophic archaea (ANME) and sulfate reducing bacteria. An additional methane sink, i.e., iron oxide coupled AOM (Fe-AOM), has been suggested to be active in the methanic zone of marine sediments. Geochemical signatures below the SMT such as high dissolved iron, low to undetectable sulfate and high methane concentrations, together with the presence of iron oxides are taken as prerequisites for this process. So far, Fe-AOM has neither been proven in marine sediments nor have the governing key microorganisms been identified. Here, using a multidisciplinary approach, we show that Fe-AOM occurs in iron oxide-rich methanic sediments of the Helgoland Mud Area (North Sea). When sulfate reduction was inhibited, different iron oxides facilitated AOM in long-term sediment slurry incubations but manganese oxide did not. Especially magnetite triggered substantial Fe-AOM activity and caused an enrichment of ANME-2a archaea. Methane oxidation rates of 0.095 ± 0.03 nmol cm–3 d–1 attributable to Fe-AOM were obtained in short-term radiotracer experiments. The decoupling of AOM from sulfate reduction in the methanic zone further corroborated that AOM was iron oxide-driven below the SMT. Thus, our findings prove that Fe-AOM occurs in methanic marine sediments containing mineral-bound ferric iron and is a previously overlooked but likely important component in the global methane budget. This process has the potential to sustain microbial life in the deep biosphere.

Abstract Background To study MMP activity in vivo in disease, several radiolabeled MMP inhibitors functioning as radiotracers have been evaluated by means of SPECT and PET. Unfortunately, most of them suffer from metabolic instability, mainly hepatobiliary clearance and insufficient target binding. The introduction of a fluorine atom into MMPIs could contribute to target binding, enhance the metabolic stability and might shift the clearance towards more renal elimination. Recently developed α-sulfonylaminohydroxamic acid based γ-fluorinated inhibitors of MMP-2 and -9 provide promising fluorine interactions with the enzyme active site and high MMP inhibition potencies. The aim of this study is the (radio)synthesis of a γ-fluorinated MMP-2 and -9 inhibitor to evaluate its potential as a radiotracer to image MMP activity in vivo. Results Two new fluorine-containing, enantiomerically pure inhibitors for MMP-2 and -9 were synthesized in a six step sequence. Both enantiomers exhibited equal inhibition potencies in the low nanomolar and subnanomolar range. LogD value indicated better water solubility compared to the CGS 25966 based analog. The most potent inhibitor was successfully radiofluorinated. In vivo biodistribution in wild type mice revealed predominantly hepatobiliary clearance. Two major radioactive metabolites were found in different organs. Defluorination of the radiotracer was not observed. Conclusion (Radio)synthesis of a CGS based γ-fluorinated MMP inhibitor was successfully accomplished. The (S)-enantiomer, which normally shows no biological activity, also exhibited high MMP inhibition potencies, which may be attributed to additional interactions of fluorine with enzyme’s active site. Despite higher hydrophilicity no significant differences in the clearance characteristics compared to non-fluorinated MMPIs was observed. Metabolically stabilizing effect of the fluorine was not monitored in vivo in wild type mice.

Sung-Chan Jang,1,2,* Sung-Min Kang,1,* Jun Young Lee,3,* Seo Yeong Oh,1 AT Ezhil Vilian,4 Ilsong Lee,1,2 Young-Kyu Han,4 Jeong Hoon Park,3 Wan-Seob Cho,5,* Changhyun Roh,2,6 Yun Suk Huh1 1Department of Biological Engineering, Biohybrid Systems Research Center (BSRC), Inha University, Incheon, 2Biotechnology Research Division, 3Radiation Instrumentation Research Division, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), Jeongeup, 4Department of Energy and Materials Engineering, Dongguk University, Seoul, 5Laboratory of Toxicology, Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, 6Radiation Biotechnology and Applied Radioisotope Science, University of Science and Technology (UST), Daejeon, Republic of Korea *These authors contributed equally to this work Introduction: Positron emission tomography (PET) tracers has the potential to revolutionize cancer imaging and diagnosis. PET tracers offer non-invasive quantitative imaging in biotechnology and biomedical applications, but it requires radioisotopes as radioactive imaging tracers or radiopharmaceuticals. Method: This paper reports the synthesis of 18F-nGO-PEG by covalently functionalizing PEG with nano-graphene oxide, and its excellent stability in physiological solutions. Using a green synthesis route, nGO is then functionalized with a biocompatible PEG polymer to acquire high stability in PBS and DMEM. Results and discussion: The radiochemical safety of 18F-nGO-PEG was measured by a reactive oxygen species and cell viability test. The biodistribution of 18F-nGO-PEG could be observed easily by PET, which suggested the significantly high sensitivity tumor uptake of 18F-nGO-PEG and in a tumor bearing CT-26 mouse compared to the control. 18F-nGO-PEG was applied successfully as an efficient radiotracer or drug agent in vivo using PET imaging. This article is expected to assist many researchers in the fabrication of 18F-labeled graphene-based bio-conjugates with high reproducibility for applications in the biomedicine field. Keywords: graphene oxide, nanocomposite, imaging, radiotracer

Key Clinical Message This case highlights the role of molecular breast imaging (MBI) in evaluating persistent clinical concerns after a negative diagnostic mammogram and ultrasound. MBI is especially useful in the diagnosis of invasive lobular carcinoma due to its occult nature on conventional imaging modalities.

Purpose of Review: Goal of this review article was to summarize and evaluate the current developments in nuclear medicine cardiovascular imaging with focus on PET/MR imaging. Furthermore, it should highlight recent topics of interest, such as sarcoidosis, inflammation, and cardiac amyloidosis for instance, which have not properly characterized with PET/MRI yet. Recent Findings: In the last years there have been advances in experimental tracers and clinical research especially for inflammatory cardiac diseases. Most articles still focus PET/CT rather than PET/MRI, which is mostly due to a limited number of PET/MRI centers worldwide. Nonetheless, PET/MRI is gaining more importance as a diagnostic tool for cardiac sarcoidosis and cardiac amyloidosis. Summary: A decade after the introduction of commercially available simultaneous PET/MRI scanner, the big breakthrough has stayed away. Still, combined cardiac imaging has shown beneficial performance in various studies. Recent data suggests that in inflammatory diseases, PET and MRI works synergistically. But there are still many unanswered questions, e.g.: Which tracer has the best performance? What is the impact on patient management? Despite that there is great dynamism in that field of research with high potential for PET/MRI. [ABSTRACT FROM AUTHOR]

Aims Cardiovascular thrombosis is responsible a quarter of deaths annually worldwide. Current imaging methods for cardiovascular thrombosis focus on anatomical identification of thrombus but cannot determine thrombus age or activity. Molecular imaging techniques hold promise for identification and quantification of thrombosis in vivo. Our objective was to assess a novel optical and positron-emitting probe targeting Factor XIIIa (ENC2015) as biomarker of active thrombus formation. Methods and results Optical and positron-emitting ENC2015 probes were assessed ex vivo using blood drawn from human volunteers and passed through perfusion chambers containing denuded porcine aorta as a model of arterial injury. Specificity of ENC2015 was established with co-infusion of a factor XIIIa inhibitor. In vivo 18F-ENC2015 biodistribution, kinetics, radiometabolism, and thrombus binding were characterized in rats. Both Cy5 and fluorine-18 labelled ENC2015 rapidly and specifically bound to thrombi. Thrombus uptake was inhibited by a factor XIIIa inhibitor. 18F-ENC2015 remained unmetabolized over 8 h when incubated in ex vivo human blood. In vivo , 42% of parent radiotracer remained in blood 60 min post-administration. Biodistribution studies demonstrated rapid clearance from tissues with elimination via the urinary system. In vivo, 18 F-ENC2015 uptake was markedly increased in the thrombosed carotid artery compared to the contralateral patent artery (mean standard uptake value ratio of 2.40 vs. 0.74, P  < 0.0001). Conclusion  ENC2015 rapidly and selectively binds to acute thrombus in both an ex vivo human translational model and an in vivo rodent model of arterial thrombosis. This probe holds promise for the non-invasive identification of thrombus formation in cardiovascular disease. [ABSTRACT FROM AUTHOR]

High-affinity monoamine transporters are targets for prescribed medications and stimulant drugs of abuse. Therefore, assessing monoamine transporter activity for candidate medications and newly-emerging drugs of abuse provides essential information for industry, academia, and public health. Radiotracer binding and uptake inhibition are the gold standard assays for determining drug–transporter interaction profiles. The combined results from such assays yield a unique biochemical fingerprint for each compound. Over time, different assay methods have been developed to assess transporter activity, and the comparability of data across various assay platforms remains largely unclear. Here, we compare the effects of six well-established stimulants in two different cell-based uptake inhibition assays, one method using adherent cells and the other using suspended cells. Furthermore, we compare the data from transfected cell lines derived from different laboratories and data reported from rat synaptosomes. For transporter inhibitors, IC50 values obtained by the two experimental methods were comparable, but using different transfected cell lines yielded disparate results. For transporter substrates, differences between the two cell lines were less pronounced but the drugs displayed different inhibition potencies when evaluated by the two methods. Our study illustrates the inherent limitations when comparing transporter inhibition data from different laboratories and stresses the importance of including appropriate control experiments with reference compounds when investigating new drugs of interest. [ABSTRACT FROM AUTHOR]

Bromodomain and extra-terminal domain (BET) family proteins play a vital role in the epigenetic regulation process by interacting with acetylated lysine (Ac-K) residues in histones. BET inhibitors have become promising candidates to treat various diseases through the inhibition of the interaction between BET bromodomains and Ac-K of histone tails. With a molecular imaging probe, noninvasive imaging such as positron emission tomography (PET) can visualize the distribution and roles of BET family proteins in vivo and enlighten our understanding of BET protein function in both healthy and diseased tissue. We radiolabeled the potent BET inhibitor INCB054329 by N -methylation to make 11C]PB003 as a BET PET radiotracer. The bioactivity evaluation of unlabeled PB003 in vitro was performed to confirm its binding affinity for BRDs, then the PET/CT imaging in rodents was performed to evaluate the bioactivity of 11C]PB003 in vivo. In our in vitro evaluation, PB003 showed a high BET binding affinity for BRDs (K d = 2 nM, 1.2 nM, and 1.2 nM for BRD2, BRD3, and BRD4, respectively). In vivo PET/CT imaging demonstrated that 11C]PB003 has favorable uptake with appropriate kinetics and distributions in main peripheral organs. Besides, the blockade of 11C]PB003 binding was found in our blocking study which indicated the specificity of 11C]PB003. However, the BBB penetration and brain uptake of 11C]PB003 was limited, with only a maximum 0.2% injected dose/g at ~2 min post-injection. The imaging results in rodents in vivo demonstrate that 11C]PB003 binds to BET with high selectivity and specificity and has favorable uptake in peripheral organs. However, the low brain uptake of 11C]PB003 limits the visualization of brain regions indicating the efforts are still needed to discover the new BET imaging probes for brain visualization. [ABSTRACT FROM AUTHOR]

The aim of this study is to find the optimum conditions of labeling luteolin flavonoid compounds with technetium-99m (99mTc) to meet the purity requirements stated in the United States Pharmacopeia. This compound is expected to be a potential radiotracer compound for diagnosing cancer. The optimization method in labeling luteolin with technetium determines the parameters such as pH, SnCl2.2H2O, genistein concentration, and incubation time. Optimization results of Technetium-99m-luteolin labeling obtained optimum pH conditions 8, the amount of SnCl2.2H2O as a reducing agent 60 μL, the optimum amount of luteolin 6 mg/ml, and the optimum incubation time is 30 min. This optimum condition obtained a99mTc-Luteolin radiochemical purity yield of 94.15%. The radiochemical purity percentage of the99mTc-Luteolin compound has fulfilled the requirements listed at United States Pharmacopeia, which is ≥90%. [ABSTRACT FROM AUTHOR]

The suitability of novel positron emission tomography (PET) radioligands for quantitative in vivo imaging is affected by various physicochemical and pharmacological parameters. In this study, the combined effect of binding affinity, lipophilicity, protein binding and blood plasma level on cerebral pharmacokinetics and PET imaging characteristics of three xanthine-derived A 1 adenosine receptor (A 1 AR) radioligands was investigated in rats. A comparative evaluation of two novel cyclobutyl-substituted xanthine derivatives, 8-cyclobutyl-3-(3-18F]fluoropropyl)-1-propylxanthine (18F]CBX) and 3-(3-18F]fluoropropyl)-8-(1-methylcyclobutyl)-1-propylxanthine (18F]MCBX), with the reference A 1 AR radioligand 8-cyclopentyl-3-(3-18F]fluoropropyl)-1-propylxanthine (18F]CPFPX) was conducted. This evaluation included in vitro competition binding assays, in vitro autoradiography and in vivo PET imaging. Differences in cerebral pharmacokinetics and minimal scan duration required for quantification of cerebral distribution volume (V T) were assessed. Measured K i values of non-labeled CBX, MCBX and CPFPX were 10.0 ± 0.52 nM, 3.3 ± 0.30 nM and 1.4 ± 0.15 nM, respectively (n = 3–4). In vitro autoradiographic binding patterns in rat brain were comparable between the radioligands, as well as the fraction of non-specific binding (1.0–1.9%). In vivo cerebral pharmacokinetics of the novel cyclobutyl-substituted xanthines differed considerably from that of 18F]CPFPX. Brain uptake and V T of 18F]CBX were substantially lower despite the higher concentration of radiotracer in plasma. 18F]MCBX showed comparable uptake and V T , but faster cerebral kinetics than 18F]CPFPX. However, the faster kinetics of 18F]MCBX did not enable the quantification of cerebral V T in a shorter scan time. The combined effect of individual physicochemical and pharmacological properties of a radiotracer on its PET imaging characteristics cannot be readily predicted. In vivo performance of the xanthine A 1 AR radioligands was mainly influenced by binding affinity; plasma concentrations and cerebral kinetics were of secondary importance. [ABSTRACT FROM AUTHOR]

To investigate whether combining two independent tracers increases the SLN-detection rate in cervical cancer. Consecutive women with early stage cervical cancer planned for a robotic radical hysterectomy or a robotic radical trachelectomy with sentinel lymph node (SLN) detection were included. After cervical injections of Indocyanine green (ICG) and Tc99-nanocolloid (Tc99), near-infrared fluorescence imaging and a gamma probe were used to identify SLNs in the upper and lower paracervical pathways (UPP/LPP). A strict surgical algorithm was adhered to and the SLNs were defined as SLN-ICG, SLN-ICG+Tc99 or SLN-Tc99. In FIGO-stage ≥IA2 cancers a full pelvic lymph node dissection (PLND) was performed after detection of SLNs. The primary endpoint was the SLN detection rate per tracer and combination of tracers. Secondary endpoints were sensitivity and mapping rates of the SLN algorithm per tracer and combination of tracers. In the sixty-five analyzed women, the bilateral mapping rate was 98.5% for ICG and 60% for Tc99 (p < 0.01). Combining the tracers did not increase the bilateral detection rate. In three women (5%) Tc99 identified ICG-negative non-metastatic SLNs without impact on the bilateral detection rate. Eight women (12%) had lymph node metastases (LNMs), all had at least one metastatic SLN. Seven (35%) of the 20 metastatic SLNs were detected by ICG only and 12 (60%) were ICG and Tc99 positive. SLN detection rate was significantly higher using ICG compared with Tc99. ICG identified all patients with LNMs. Combining ICG and Tc99 did not improve the bilateral detection rate of SLNs. • ICG resulted in a 98.5% bilateral SLN detection rate. • Tc99 resulted in a 60% bilateral SLN detection rate. • Combination of tracers did not increase SLN-detection rate. • All node positive patients were identified through an ICG-positive SLN. [ABSTRACT FROM AUTHOR]

The flux of methane, a potent greenhouse gas, from the seabed is largely controlled by anaerobic oxidation of methane (AOM) coupled to sulfate reduction (S-AOM) in the sulfate methane transition (SMT). S-AOM is estimated to oxidize 90% of the methane produced in marine sediments and is mediated by a consortium of anaerobic methanotrophic archaea (ANME) and sulfate reducing bacteria. An additional methane sink, i.e., iron oxide coupled AOM (Fe-AOM), has been suggested to be active in the methanic zone of marine sediments. Geochemical signatures below the SMT such as high dissolved iron, low to undetectable sulfate and high methane concentrations, together with the presence of iron oxides are taken as prerequisites for this process. So far, Fe-AOM has neither been proven in marine sediments nor have the governing key microorganisms been identified. Here, using a multidisciplinary approach, we show that Fe-AOM occurs in iron oxide-rich methanic sediments of the Helgoland Mud Area (North Sea). When sulfate reduction was inhibited, different iron oxides facilitated AOM in long-term sediment slurry incubations but manganese oxide did not. Especially magnetite triggered substantial Fe-AOM activity and caused an enrichment of ANME-2a archaea. Methane oxidation rates of 0.095 ± 0.03 nmol cm–3 d–1 attributable to Fe-AOM were obtained in short-term radiotracer experiments. The decoupling of AOM from sulfate reduction in the methanic zone further corroborated that AOM was iron oxide-driven below the SMT. Thus, our findings prove that Fe-AOM occurs in methanic marine sediments containing mineral-bound ferric iron and is a previously overlooked but likely important component in the global methane budget. This process has the potential to sustain microbial life in the deep biosphere. [ABSTRACT FROM AUTHOR]

The rare earth elements including terbium are highly important in high-tech applications. Considering the commercial aspects of terbium metal, we report its sequestration from their solutions by 1-(2-pyridylazo)-2-naphthol (PAN) doped hybrid silica. This material can adsorb about 97% of Tb(III) ions (2.01 × 10−6 M) at pH 8 within 30 min, using 50 mg of the adsorbent. The adsorption process is modeled with Freundlich, D-R and Langmuir isotherms. The ion-exchange constants such as Q (0.43 ± 0.1μmol g−1, b (0.37 ± 0.04 × 104 dm3 mol−1), l/n (0.42 ± 0.1), Cm (37.9 ± 4.2 mmol g−1), Xm (2.8 ± 0.8 mmol g−1), β (− 0.0025 ± 0.00012 kJ2 mol−2) and energy E (14 ± 0.3 kJ mol−1) were computed from these models. Thermodynamic parameters like ΔH (39.6 ± 0.2 J mol−1 K−1), ΔS (148 ± 0.3 J mol−1 K−1) and ΔG (− 42.10 ± 0.2 J mol−1(298 K)) reflected that Tb+3 adsorption is spontaneous and endothermic. EDTA, Fe(III),oxalate and citrate reduced the adsorption significantly. Density functional theory simulations show that adsorption of PAN over SiO2 takes place due to strong intermolecular hydrogen bonding. The energy gap of the SiO2 surface was significantly decreased and favored the orbital interactions and charge transfer effects of the metal adsorption over the PAN/SiO2 surface. [ABSTRACT FROM AUTHOR]

Gallium-68 is an important radionuclide for positron emission tomography (PET) with steadily increasing applications of 68Ga-based radiopharmaceuticals for clinical use. Current 68Ga sources are primarily 68Ge/68Ga-generators, along with successful attempts of 68Ga production using a cyclotron. This study evaluated cyclotron 68Ga production and automated separation using expeditiously manufactured solid targets, demonstrates an order of magnitude improvement in yield compared to 68Ge/68Ga generators, and presents a convenient alternative to existing cyclotron production processes. A comparison of radiolabeling and preclinical PET imaging was performed with both cyclotron and generator produced 68Ga. 100 mg enriched 68Zn (99.3% 68Zn, 0.48% 67Zn, 0.1% 66Zn) pellets pressed on silver discs were bombarded for 20–75 min using 12.5 MeV proton beam energies and 10–30 μA currents. 68Ga was separated using an automated TRASIS AllinOne synthesizer employing AG 50W-X8 and UTEVA resins. Post-separation recovery of the 68Zn by electrolysis yielded 76.7 ± 4.3%. Radionuclidic purity of cyclotron-produced 68Ga was investigated with gamma spectroscopy using a HPGe-detector. Radiolabeling was investigated using the macrocyclic chelator DOTA and the bombesin-derived peptide NOTA-BBN2. PET imaging was performed using [68Ga]Ga-NOTA-BBN2 in a PC3 xenograft model. 600 μA·min fresh and recycled quadruplet 68Zn target irradiations (n = 8) at 12.5 MeV and 30 μA yielded 13.9 ± 1.0 GBq 68Ga; 2200 μA·min irradiations (n = 3) yielded 37.5 ± 1.9 GBq 68Ga. HPGe analysis showed EOB 0.0074% and 0.0084% of total activity of 66Ga and 67Ga, respectively. Metal impurities were 0.06 ± 0.03 μg/GBq Zn, 0.13 ± 0.007 μg/GBq Fe, and 0.02 ± 0.01 μg/GBq Al for cyclotron 68Ga. Cyclotron and 68Ge/68Ga generator 68Ga respective DOTA and NOTA-BBN2 labeling incorporations were 99.4 ± 0.0% and 99.3 ± 0.2%, and 90.4 ± 1.5% and 93.0 ± 3.6% determined by radio-thin layer chromatography (radio-TLC). Preclinical PET imaging comparison between generator and cyclotron produced 68Ga showed identical radiotracer tumor uptake and biodistribution profiles in PC3 tumor bearing mice. Cyclotron 68Ga production provides highly scalable production with equivalent or superior quality 68Ga to a 68Ge/68Ga generator, while providing identical biodistribution and tumor uptake profiles. Our described targetry is simpler and more cost-effective than existing liquid and solid targetry, enabling a turnkey production system for multi-facility distribution of cyclotron produced 68Ga. The manufacturing simplicity described has potential applications for producing other radiometals such as 44Sc. Our cost-effective method of solid target 68Ga production can enhance 68Ga production capabilities to meet the high demand for 68Ga-radiopharmaceuticals for research and clinical use. [ABSTRACT FROM AUTHOR]

Two versions of radioisotope carbon-14 labelled chlorantraniliprole, 3-bromo-N-(4-chloro-2- methyl-6-(methyl[carbonyl-14C]carbamoyl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5- carboxamide (2, 55.6 mCi, radiochemical purity 99.8%, chemical purity 99.1%, specific activity 52.45 mCi/mmol) and 3-bromo-N-(4-chloro-2-methyl-6-(methylcarbamoyl)phenyl)-1-(3-chloropyridin-2-yl)- 1H-pyrazole-5-[carbonyl-14C]carboxamide (3, 58.6 mCi, radiochemical purity 99.6%, chemical purity 98.4%, specific activity 52.30 mCi/mmol), were synthesized from barium [14C]carbonate via eight-step radioactive reactions including Grignard reaction, nucleophilic substitution, amination reaction, condensation, and etc. Pure C-14 labelled products were obtained after RP-HPLC purification in the overall radiochemical yield of 32% and 52%, respectively. The products were characterized by ESI-MS, 1H NMR and HPLC-FSA. Their technical data was determined by TLC-IIA, HPLC-LSC, HPLCFSA/ PDA/MS and LSC, respectively. These products could be used as radiotracers and meet therequirement of the study on the metabolism of chlorantraniliprole for registration in China. [ABSTRACT FROM AUTHOR]

Iron (Fe) and sulfur (S) interaction was studied in bread and durum wheat by using radiotracers (59Fe and 35S). The results showed a higher uptake of 35S under Fe+ than Fe− which provides irrefutable evidence for the role of Fe in determining plant S uptake particularly under S deficiency. Under Fe deficiency, the 59Fe uptake was higher under the S2 than S1 and S0 condition, which may be attributed to a favorable regulation of phytosiderophores biosynthesis by S. This suggests that Fe and S synergistically interact and may regulate their respective uptake by inducing SULTR1; 1, high affinity sulphate transporters. [ABSTRACT FROM AUTHOR]

The pulp and paper industry is highly dependent on water for most of its processes, producing a significant amount of wastewater that should be treated to comply with environmental standards before its discharge into surface-water reservoirs. The wastewater generated primarily consists of substantial amounts of organic, inorganic, toxic and pathogenic compounds in addition to nutrients, which are treated in an effluent treatment plant that often combines primary, secondary, tertiary and advanced treatments. However, the treatment methods vary from industry to industry according to the process utilized. The effective performance of effluent treatment plants is crucial from both environmental and economic points of view. Radiotracer techniques can be effectively used to optimize performance and detect anomalies like dead zones, bypassing, channelling, etc. in wastewater treatment plants. Experiments on the distribution of residence time were performed on the aeration tank and secondary clarifier of a full-scale pulp and paper mill to study the flow behaviour as well as locate system anomalies and hence evaluate the performance of the treatment plants using the radiotracer I-131. The convolution method was applied to model the system with an imperfect impulse radiotracer input. The aeration tank was working efficiently in the absence of any dead zones or bypassing. Various hydrodynamic models available in the literature were applied on the aeration tank and secondary clarifier to obtain the hydraulic representation of the systems.

Gamma scanning and radiotracer applications are very effective and inexpensive tools to understand and optimize the process as well as troubleshoot the various types of problems in many chemical, petrochemical industries and refineries. These techniques are non-invasive; hence, the problems can be pinpointed online, which leads to reduce the downtime, schedule the shutdown and maintenance of the plant equipment, rendering huge economic benefits. In a leading refinery of India, the catalytic cracking unit (CCU) was malfunctioning. It was suspected by the refinery engineers that the catalyst powder was being carried over to the fractionator, which could have led to erosion of the fractionator column internals resulting in their rupture, and consequentially, to the fire hazard. To understand the flow behaviour of the catalyst powder and to ensure the mechanical integrity, catalyst accumulation and choking, both radiotracer study and gamma scanning of the CCU reactor was carried out. The reactor consists of a riser, three primary cyclones and three secondary cyclones. Gamma scanning of the reactor was carried out with the help of an automatic gamma scanner using 1.8 GBq of Co-60 sealed source. Results showed that the catalyst powder was accumulated in one of the secondary cyclones and uneven density distribution was observed in another secondary cyclone. The radiotracer study was carried out using the irradiated catalyst powder as a radiotracer, which contains 0.9 GBq of Na-24. The radiotracer was injected in the reactor through the specially fabricated injection system. Radiation measurement was done using the thermally insulated and collimated NaI(Tl) scintillation detectors located at various strategic locations coupled to a multi-detector data acquisition system. The data were mathematically analysed. It was confirmed that the catalyst powder was accumulated in one of the secondary cyclones with no flow downwards. This resulted in excess powder available to travel along with hydrocarbon towards fractionator. Since the quantity of powder released through the hydrocarbon outlet of CCU was higher than the designed value, the catalyst powder was observed in various zones of the fractionator. Mathematical modelling of the radiotracer data obtained at various locations corroborated the scanning results; also, the flow pattern was obtained. Partially blocked secondary cyclone showed plug flow with recirculation; normal working cyclone had plug flow behaviour and the vortex breaker showed parallel flow.

Herein we report the mild and rapid fluorodesulfurization of thionoesters using only silver(I) fluoride. This reaction demonstrates excellent functional group tolerance and complements existing strategies for difluoroalkyl ether synthesis, which rely on toxic and often dangerous reagents that demonstrate limited functional group compatibility. We additionally report the translation of this finding to the production of 18F‐labelled difluoroalkyl ethers using fluoride‐derived [18F]AgF. This new process should enable the synthesis of a wide range of difluoroalkyl ethers with applications in medicinal and materials chemistry, and radiotracer production. [ABSTRACT FROM AUTHOR]

• Novel, precise method to assess intradermal (ID) fluid delivery capacity of devices. • Hypodermic needles and hollow microneedles evaluated ex vivo and in vivo. • Captured fluid injected/backflow at high sensitivity compared to gravimetric methods. • Use of low 99mTcO 4 − radioactivity provided sub-nanoliter measurement resolution. • ID delivery device development facilitated by 99mTcO 4 − injections. A method was developed and validated to determine the intradermal (ID) fluid delivery potential of several ID devices, including hollow microneedles. The novel method used water soluble technetium-99 m pertechnetate (99mTcO 4 −) diluted in normal saline to measure the volume of fluid delivered to and remaining in the skin. The fluid that back-flowed to the skin surface and the fluid left on the device surface were also quantified, thus capturing all fluid volumes deposited during intradermal injections. The technique described in this manuscript was used to assess the injection performance of conventional hypodermic needles and hollow microneedles ex vivo using porcine skin and in vivo with a rat model. Since only a small fraction, 1.1%, of the water-soluble tracer remained bound to the skin when applied topically, the technique can be used to differentiate between injected fluid and backflow. Counting of gamma radiation from 99mTcO 4 − provided sub-nanoliter resolution for volume measurements, making the proposed method powerful, sensitive, and suitable for the assessments of ID injection devices, particularly for vaccine delivery. [ABSTRACT FROM AUTHOR]

Diabetic patients often experience chronic inflammation and fibrosis in their cardiac tissues, highlighting the pressing need for the development of sensitive diagnostic methods for longitudinal assessment of diabetic cardiomyopathy. This study aims to evaluate the significance of an inflammatory marker known as translocator protein (TSPO) in a positron emission tomography (PET) protocol for longitudinally monitoring cardiac dysfunction in a diabetic animal model. Additionally, we compared the commonly used radiotracer, 18F-fluoro-2-deoxy- d -glucose (18F-FDG). Fourteen 7-week-old female Sprague-Dawley rats were used in this study. Longitudinal PET experiments were conducted using 18F- N -2-(2-fluoroethoxy)benzyl)- N -(4-phenoxypyridin-3-yl)acetamide (18F-FEPPA) (n = 3), the TSPO radiotracer, and 18F-FDG (n = 3), both before and after the onset of diabetes. Histological and immunohistochemical staining assays were also conducted in both the control (n = 4) and diabetes (n = 4) groups. Results indicated a significant increase in cardiac tissue uptake of 18F-FEPPA after the onset of diabetes (P < 0.05), aligning with elevated TSPO levels observed in diabetic animals according to histological data. Conversely, the uptake of 18F-FDG in cardiac tissue significantly decreased after the onset of diabetes (P < 0.05). These findings suggest that 18F-FEPPA can function as a sensitive probe for detecting chronic inflammation and fibrosis in the cardiac tissues of diabetic animals. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] In recent years, PD-1/PD-L1 checkpoint blockade immunotherapy with remarkable efficacy has set off a heat wave. The expression level of PD-L1, which plays a predictive role in anti-PD-1/PD-L1 therapy, could be quantified by noninvasive imaging with radiotracers. Herein, we introduced the synthesis and preliminary biological evaluation of a novel 99mTc-labeled small molecule radiotracer [99mTc]G 3 C-CBM for PD-L1 imaging. [99mTc]G 3 C-CBM was achieved with high radiochemical purity (>96 %) and remained good stability in PBS and FBS. In competitive combination experiment, [99mTc]G 3 C-CBM was displaced by increasing concentrations of unlabeled G 3 C-CBM, resulting in an IC 50 value of 41.25±2.23 nM for G 3 C-CBM. The uptake of [99mTc]G 3 C-CBM in A375-hPD-L1 cells (17.51±2.08 %) was approximately 6.47 folds of that in A375 cells (2.71±0.36 %) after co-incubation for 2 h. The biodistribution results showed that the radioactivity uptake in A375-hPD-L1 tumor reached the maximum (0.35±0.01 %ID/g) at 2 h post injection, and the optimum tumor/muscle ratio of 2.94±0.29 occurred at the same time. In addition, [99mTc]G 3 C-CBM was quickly cleared from the blood with a clearance half-life of just 119.25 min. These results indicate that [99mTc]G 3 C-CBM is a potential SPECT PD-L1 imaging agent and is worthy of further study. [ABSTRACT FROM AUTHOR]