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Fast and accurate detection of traffic signs is crucial for the development of intelligent transportation systems. To address the issue of false detection and missing detection of small traffic signs in complex scenes, this paper proposes a YOLO-SG model based on YOLOv5. The YOLO-SG approach employs SPD-Conv as a down-sampling structure to mitigate the loss of feature information during the down-sampling process. This enhances the detection performance of small objects in complex scenes and improves the generalization and robustness of the model. The feature extraction architecture uses GhostNet, which effectively reduces the number of model parameters and weight, enhancing the feasibility of practical model deployment. Furthermore, this study optimizes the output feature structure by introducing a small object detection layer and removing the large object detection layer, enabling the detection of small objects. Extensive experiments conducted on the GTSDB and TT100K datasets demonstrate that YOLO-SG exhibits excellent detection performance. On the GTSDB dataset, YOLO-SG achieved a 2.3% increase in mAP compared to the baseline network, while reducing the number of parameters by 42%. Similarly, on the TT100K dataset, YOLO-SG increased mAP by 6.3% and reduced the number of parameters by 43%. These experimental results showcase the effectiveness and accuracy of YOLO-SG, particularly in detecting small traffic signs. [ABSTRACT FROM AUTHOR]

The asialoglycoprotein receptor(ASGPR) is abundantly expressed on the surface of hepatocytes where it recognizes and endocytoses glycoproteins with galactosyl and N -acetylgalactosamine groups. ASGPR not only express on the surface of hepatocytes, but also express in several tumor cells (HepG2, A549 and HCT116). The purpose of this study was to develop a ASGPR-specific radiofluorinated ligand for positron emission tomography (PET) imaging in several tumor models. The radiosynthesis of [18F]FPGalNAc was initiated with fluorine-18 and 5-(p-toluenesulfonyl)-1-yne. The obtained 5-[18F]fluoro-1-pentyne intermediate was then reacted with 2-acetamido-2-deoxy-β- d -galactopyranosyl azide using "click chemistry" to produce the final product. The K d of the product was determined in HepG2 cells at a range of concentrations of [18F]FPGalNAc. Cellular uptake and blocking experiments were also performed. In vivo biodistribution studies were performed in nude mice bearing HCT116 tumor and micro positron emission tomography/computed tomography (PET/CT) evaluations were then performed in tumor-bearing mice (HepG2, HCT116) models. The radiosynthesis of [18F]FPGalNAc required 50 min with 5–6% RCY (radiochemical yield). The K d of [18F]FPGalNAc to ASGPR in HepG2 cells was 0.25 ± 0.02 mM. Uptake values of 0.29% were observed within 30 min of incubation with HepG2 cells, which could be blocked by 200 mM d (+)-galactose (< 0.13%). The data of biodistribution revealed that the uptake of [18F]FPGalNAc was higher in kidneys and liver, and lower in muscle, bone and brain. In vivo micro PET studies, both HCT116 and HepG2 tumors showed high uptake for [18F]FPGalNAc, the radio of tumor/muscle (T/M) was 3.7 and 3.91, respectively. In vitro assays and in vivo PET/CT imaging and biodistribution studies showed that [18F]FPGalNAc represents a promising tumor imaging agent that can provide insight into ASGPR related disease. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) has gained significant attention as a therapeutic target. Several EGFR targeting drugs (Gefitinib and Erlotinib) have been approved by US Food and Drug Administration (FDA) and have received high approval in clinical treatment. Nevertheless, the curative effect of these medicines varied in many solid tumors because of the different levels of expression and mutations of EGFR. Therefore, several PET radiotracers have been developed for the selective treatment of responsive patients who undergo PET/CT imaging for tyrosine kinase inhibitor (TKI) therapy. In this study, a novel fluorine-18 labeled 4-anilinoquinazoline based PET tracer, 1 N -(3-(1-(2- 18 F-fluoroethyl)-1 H -1,2,3-triazol-4-yl)phenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine ( 18 F-FEA-Erlotinib), was synthesized and biological evaluation was performed in vitro and in vivo. 18 F-FEA-Erlotinib was achieved within 50 min with over 88% radiochemical yield (decay corrected RCY), an average specific activity over 50 GBq/μmol, and over 99% radiochemical purity. In vitro stability study showed no decomposition of 18 F-FEA-Erlotinib after incubated in PBS and FBS for 2 h. Cellular uptake and efflux experiment results indicated the specific binding of 18 F-FEA-Erlotinib to HCC827 cell line with EGFR exon 19 deletions. In vivo, Biodistribution studies revealed that 18 F-FEA-Erlotinib exhibited rapid blood clearance both through hepatobiliary and renal excretion. The tumor uptake of 18 F-FEA-Erlotinib in HepG2, HCC827, and A431 tumor xenografts, with different EGFR expression and mutations, was visualized in PET images. Our results demonstrate the feasibility of using 18 F-FEA-Erlotinib as a PET tracer for screening EGFR TKIs sensitive patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel peptide imaging agent Al[18F]-NOTA-IPB-PDL1P has been synthesized. • Al[18F]-NOTA-IPB-PDL1P as a molecular probe that specifically targets PD-L1 expressed in tumors (HCT116, PC3). • Compared with [64Cu]-TPP-1 and [64Cu]-PEG-TPP-1, Al[18F]-NOTA-IPB-PDL1P showed higher tumor uptake and more longer tumor retention. PD-L1 is widely expressed in a variety of tumors, including NSCLC, melanoma, renal cell carcinoma, gastric cancer, hepatocellular as well as cutaneous and various leukemias, multiple myeloma and so on. Herein, we designed a novel peptide imaging agent (Al[18F]-NOTA-IPB-PDL1P) that specifically targets PD-L1 expressed in tumors. The overall radiochemical yield of Al[18F]-NOTA-IPB-PDL1P from 18F- was 10–15% (corrected radiochemical yield) within 20 min and the radiochemical purity of Al[18F]-NOTA-IPB-PDL1P was > 95% with a molar activity of 44.4–64.8 GBq/μmol. The lipophilicity logP value of Al[18F]-NOTA-IPB-PDL1P at pH 7.4 was −1.768 ± 0.007 (n = 3). In the cellular uptake experiment, both HCT116 and PC3 cells dispalyed high uptake to Al[18F]-NOTA-IPB-PDL1P. The results of biodistribution showed that the uptake of Al[18F]-NOTA-IPB-PDL1P was high in kidneys, gall bladder and lung, and low in muscle and brain. In vivo micro PET studies, both HCT116 and PC3 tumors displayed high uptake for Al[18F]-NOTA-IPB-PDL1P, the tumor/muscle (T/M) radio was 2.93 and 3.57 respectively at 120 min. All the results indicate that Al[18F]-NOTA-IPB-PDL1P may have potential to be a PET imaging agent of tumors with high PD-L1 expression. [ABSTRACT FROM AUTHOR]

In aerial image detection, difficulties in feature extraction and low detection accuracy arise due to background interference, occlusion, and the presence of multiple small objects. This paper proposes a DM-YOLOX aerial object target detection method with intensive attention mechanism. Firstly, the proposed approach incorporates coordinate attention (CA) and a dense connection method into the backbone network architecture, enabling adaptive channel weighting throughout the feature extraction process. This facilitates the enhancement of significant features while suppressing less relevant ones, thereby augmenting the network's capacity to represent object features and ensuring retention and reinforcement of key features. Secondly, the multibranch extraction module (MBE) is incorporated into the feature fusion network to enhance the network's ability in extracting multi-scale feature information from images with extensive coverage, thereby enhancing the detection accuracy and efficiency of small- and medium-sized objects in complex scenes. Finally, the utilization of SIoU instead of IoU as the bounding box loss function effectively addresses the issue of mismatch between real and predicted boxes, leading to accelerated network convergence and improved performance during model training. After training and testing on the VisDrone 2019 dataset, this method effectively detects small objects in complex environments. The DM-YOLOX model shows a significant improvement of 2.7% in mAP compared to the baseline network, while achieving an 8% increase in frames per second (FPS). [ABSTRACT FROM AUTHOR]

Background: Conventional clinical PET scanners typically have an axial field of view (AFOV) of 15–30 cm, resulting in limited coverage and relatively low photon detection efficiency. Taking advantage of the development of long-axial PET/CT, the uEXPLORER PET/CT scanner with an axial coverage of 194 cm increases the effective count rate by approximately 40 times compared to that of conventional PET scanners. Ordered subset expectation maximization (OSEM) is the most widely used iterative algorithm in PET. The major drawback of OSEM is that the iteration process must be stopped before convergence to avoid image degradation due to excessive noise. A new Bayesian penalized-likelihood iterative PET reconstruction, named HYPER iterative, was developed and is now available on the uEXPLORER total-body PET/CT, which incorporates a noise control component by using a penalty function in each iteration and finds the maximum likelihood solution through repeated iterations. To date, its impact on lesion visibility in patients with a full injected dose or half injected dose is unclear. The goal of this study was to determine a proper protocol for routine 18F-FDG uEXPLORER total-body PET/CT scans. Results: The uEXPLORER total-body PET/CT images reconstructed using both OSEM and HYPER iterative algorithms of 20 tumour patients were retrospectively reviewed. The quality of the 5 min PET image was excellent (score 5) for all of the dose and reconstruction methods. Using the HYPER iterative method, the PET images reached excellent quality at 1 min with full-dose PET and at 2 min with half-dose PET. The PET image reached a similar excellent quality at 2 min with a full dose and at 3 min with a half dose using OSEM. The noise in the OSEM reconstruction was higher than that in the HYPER iterative. Compared to OSEM, the HYPER iterative had a slightly higher SUVmax and TBR of the lesions for large positive lesions (≥ 2 cm) (SUVmax: up to 9.03% higher in full dose and up to 12.52% higher in half dose; TBR: up to 8.69% higher in full dose and up to 23.39% higher in half dose). For small positive lesions (≤ 10 mm), the HYPER iterative had an obviously higher SUVmax and TBR of the lesions (SUVmax: up to 45.21% higher in full dose and up to 74.96% higher in half dose; TBR: up to 44.91% higher in full dose and up to 93.73% higher in half dose). Conclusions: A 1 min scan with a full dose and a 2 min scan with a half dose are optimal for clinical diagnosis using the HYPER iterative and 2 min and 3 min for OSEM. For quantification of the small lesions, HYPER iterative reconstruction is preferred. [ABSTRACT FROM AUTHOR]

Purpose: Research on fibroblast activating protein (FAP)-targeting inhibitor (FAPI) has become an important focus for cancer imaging and radiotherapy. Quinoline-based tracers [68 Ga]FAPI-04 and [18F]FAPI-42 have been widely used for positron emission tomography (PET) imaging of most tumors. However, there exist some limitations of these tracers with high uptake in biliary duct system and unstable uptake in pancreas, unsuitable for abdominal tumors PET imaging. Here we developed a [18F]-labeled glycopeptide-containing FAPI tracer (named [18F]FAPT) for PET imaging of FAP in cancers. Methods: [18F]FAPT was synthesized manually and automatically. The competitive binding to FAP, cellular internalization, and efflux characteristics were examined in vitro using A549-FAP cells. Dynamic MicroPET and biodistribution studies of [18F]FAPT were then conducted in A549-FAP and U87MG xenograft tumor mouse models compared with [18F]FAPI-42. Five healthy volunteers and three patients with cancer underwent [18F]FAPT PET/CT. Results: Preclinical and clinical studies showed specific binding of [18F]FAPT to FAP and favorable pharmacokinetic properties with better hydrophilicity, lower uptake in biliary duct system, higher tumor uptake and longer tumor retention compared with [18F]FAPI-42. The biodistribution of [18F]FAPT in healthy volunteers and patients with cancer displayed low uptake in most normal tissues except for pancreas, thyroid and salivary gland, which could contribute to high tumor-to-background ratios in most cancers. Conclusion: [18F]FAPT is better PET tracer than [18F]FAPI-42 for imaging of biliary duct system cancer, potentially providing a tool to examine FAP expression in most cancers with high tumor-to-background ratios. [ABSTRACT FROM AUTHOR]

Background: Highly sensitive digital total-body PET/CT scanners (uEXPLORER) have great potential for clinical applications and fundamental research. Given their increasing sensitivity, low-dose scanning or snapshot imaging is now possible in clinics. However, a standardized total-body 18F-FDG PET/CT protocol is still lacking. Establishing a standard clinical protocol for total-body 18F-FDG PET/CT examination under different activity administration plans can help provide a theoretical reference for nuclear radiologists. Methods: The NEMA image quality (IQ) phantom was used to evaluate the biases of various total-body 18F-FDG PET/CT protocols related to the administered activity, scan duration, and iterations. Several objective metrics, including contrast recovery (CR), background variability (BV), and contrast-to-noise ratio (CNR), were measured from different protocols. In line with the European Association of Nuclear Medicine Research Ltd. (EARL) guidelines, optimized protocols were suggested and evaluated for total-body 18F-FDG PET/CT imaging for three different injected activities. Results: Our NEMA IQ phantom evaluation resulted in total-body PET/CT images with excellent contrast and low noise, suggesting great potential for reducing administered activity or shortening the scan duration. Different to the iteration number, prolonging the scan duration was the first choice for achieving higher image quality regardless of the activity administered. In light of image quality, tolerance of oncological patients, and the risk of ionizing radiation damage, the 3-min acquisition and 2-iteration (CNR = 7.54), 10-min acquisition and 3-iteration (CNR = 7.01), and 10-min acquisition and 2-iteration (CNR = 5.49) protocols were recommended for full-dose (3.70 MBq/kg), half-dose (1.95 MBq/kg), and quarter-dose (0.98 MBq/kg) activity injection schemes, respectively. Those protocols were applied in clinical practices, and no significant differences were observed for the SUVmax of large/small lesions or the SUVmean of different healthy organs/tissues. Conclusion: These findings support that digital total-body PET/CT scanners can generate PET images with a high CNR and low-noise background, even with a short acquisition time and low administered activity. The proposed protocols for different administered activities were determined to be valid for clinical examination and can maximize the value of this imaging type. [ABSTRACT FROM AUTHOR]

Glycogen synthase kinase 3 (GSK-3) is a potential therapeutic target for a range of neurodegenerative and psychiatric disorders. The goal of this work was to evaluate two leading GSK-3 positron emission tomography (PET) radioligands, [11C]OCM-44 and [18F]OCM-50, in non-human primates to assess their potential for clinical translation. A total of nine PET scans were performed with the two radiotracers using arterial blood sampling in adult rhesus macaques. Brain regional time-activity curves were extracted and fitted with one- and two-tissue compartment models using metabolite-corrected arterial input functions. Target selectivity was assessed after pre-administration of the GSK-3 inhibitor PF-04802367 (PF-367, 0.03–0.25 mg/kg). Both radiotracers showed good brain uptake and distribution throughout grey matter. [11C]OCM-44 had a free fraction in the plasma of 3% at baseline and was metabolized quickly. The [11C]OCM-44 volume of distribution (VT) values in the brain increased with time; VT values from models fitted to truncated 60-min scan data were 1.4–2.9 mL/cm3 across brain regions. The plasma free fraction was 0.6% for [18F]OCM-50 and VT values (120-min) were 0.39–0.87 mL/cm3 in grey matter regions. After correcting for plasma free fraction increases during blocking scans, reductions in regional VT indicated >80% target occupancy by 0.1 mg/kg of PF-367 for both radiotracers, supporting target selectivity in vivo. [11C]OCM-44 and [18F]OCM-50 warrant further evaluation as radioligands for imaging GSK-3 in the brain, though radio-metabolite accumulation may confound image analysis. [ABSTRACT FROM AUTHOR]

Purpose: [18F]FAPI-42 is a new fibroblast activation protein (FAP)-specific tracer used for cancer imaging. Here, we describe the optimal acquisition time and in vivo evaluation of [18F]FAPI-42 and compared intra-individual biodistribution, tumor uptake, and detection ability to [68Ga]Ga-FAPI-04. Methods: A total of 22 patients with various types of cancer received [18F]FAPI-42 whole-body positron emission tomography/computed tomography (PET/CT). Among them, 4 patients underwent PET/CT scans, including an early dynamic 20-min, static 1-h, and static 2-h scans. The in vivo biodistribution in normal organs and tumor uptake were semiquantitatively evaluated using the standardized uptake value (SUV) and tumor-to-background ratio (TBR). Furthermore, both [18F]FAPI-42 and [68Ga]Ga-FAPI-04 PET/CT were performed in 12 patients to compare biodistribution, tumor uptake, and tumor detection ability. Results: [18F]FAPI-42 uptake in the tumors was rapid and reached a high level with an average SUVmax of 15.8 at 18 min, which stayed at a similarly high level to 2 h. The optimal image acquisition time for [18F]FAPI-42 was determined to be 1 h postinjection. For tumor detection, [18F]FAPI-42 had a high uptake and could be clearly visualized in the lesions. Compared to [68Ga]Ga-FAPI-04, [18F]FAPI-42 had the same detectability for 144 positive lesions. In addition, [18F]FAPI-42 showed a higher SUVmax in liver and bone lesions (P < 0.05) and higher TBRs in liver, bone, lymph node, pleura, and peritoneal lesions (all P < 0.05). Conclusion: The present study demonstrates that the optimal image acquisition time of [18F]FAPI-42 is 1 h postinjection and that [18F]FAPI-42 exhibits comparable lesion detectability to [68Ga]Ga-FAPI-04. Trial registration: Chinese Clinical Trial Registry (ChiCTR2100045757). [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel peptide imaging agent [18F]AlF-NOTA-PEG 2 -Asp 2 -PDL1P was synthesized. • [18F]AlF-NOTA-PEG 2 -Asp 2 -PDL1P exhibited good hydrophilicity and had good stability both in vivo and in vitro. • [18F]AlF-NOTA-PEG 2 -Asp 2 -PDL1P showed selective accumulation in B16F10 (PD-L1-positive) tumor. Immunotherapy has brought great benefits to cancer patients, but only some patients benefit from it. Noninvasive, real-time and dynamic monitoring of the effectiveness of immunotherapy through PET imaging may provide assistance for the treatment plan of immunotherapy. In this study, we designed and synthesized a new targeted PD-L1 peptide NOTA-PEG 2 -Asp 2 -PDL1P, which was labeled with nuclide 18F to obtain a new imaging agent [18F]AlF-NOTA-PEG 2 -Asp 2 -PDL1P. The total radiochemical yield of [18F]AlF-NOTA-PEG 2 -Asp 2 -PDL1P was 13.7 % (Uncorrected radiochemical yield, n > 5). [18F]AlF-NOTA-PEG 2 -Asp 2 -PDL1P achieved high radiochemical purity (>95 %) with a molar activity more than 51.2 GBq/μmol. [18F]AlF-NOTA-PEG 2 -Asp 2 -PDL1P exhibited good hydrophilicity and had good stability both in vivo and in vitro, it can specifically targets B16F10 tumor with PD-L1 expression, and had a relatively high retention in tumor, a relatively fast clearance in vivo and a higher tumor-to-non-target ratio, all of which could make [18F]AlF-NOTA-PEG 2 -Asp 2 -PDL1P a potential tracer for PD-L1 prediction before clinical immunotherapy. [ABSTRACT FROM AUTHOR]

Lysosomal protein transmembrane 4 beta (LAPTM4B) is selectively expressed in hepatocellular carcinoma (HCC) cells and thus a potential biomarker for diagnosing HCC. In this study, we designed a novel 18F-labeled PET probe to non-invasively visualize LAPTM4B expression in mouse model of HCC tumor. A PET targeting tracer named [18F]FP-LAP2H was radio-synthesized using a LAPTM4B targeting peptide, LAP2H, coupled with 4-nitrophenyl-2-[18F]fluoropropionate ([18F]NFP). Radio-stability, cell uptake, micro PET/CT imaging and ex vivo biodistribution were performed for determining its stability, cell binding specificity, and tumor targeting in vivo. [18F]FP-LAP2H was successfully synthesized with radiochemical yields of 6–14% (decay-corrected yield) and molar activity of 10–44 GBq/μmol. The tracer showed stable (~90%) in phosphate-buffered saline, pH 7.4, and in human serum (~80%) for 2 h. In vitro cell uptake studies indicated the radioactivity accumulation in HCC cells was LAPTM4B protein-specific. Micro PET/CT demonstrated that implanted LAPTM4B positive HepG2 and BEL7402 tumors could be clearly visualized. The ex vivo biodistribution studies demonstrated that the tumor/liver ratio were 1.80 ± 0.65 and 2.09 ± 0.68 in implanted HepG2 and BEL7402 tumors respectively. Negative control and blocking experiments revealed that the radioactivity uptake in the HCC tumor was LAPTM4B protein-specific. [18F]FP-LAP2H appears to be a potential PET tracer for imaging LAPTM4B-positive HCC tumor. Further endeavors need to do to improve tumor/liver ratio. [Display omitted] • [18F]FP-LAP2H can be successfully radiosynthesis and feasible to detect LAPTM4B-positive Hepatocellular carcinoma • 18F-FP-LAP2H showed excellent biochemical characteristics in vitro and in vivo • Micro PET/CT confirmed that LAPTM4B positive HepG2 tumor can be visualized clearly in vivo with a high tumor/muscle ratio • 18F-FP-LAP2H has a potential to be a PET probe for detection of LAPTM4B-positive HCC [ABSTRACT FROM AUTHOR]

Facile automatic production is important for the application of prostate-specific membrane antigen (PSMA) tracers in clinical practice. We developed a new 18F-AlF-labelled PSMA probe—18F-AlF-PSMA-NF—and explore its automated production method and potential value in clinical settings. 18F-AlF-PSMA-NF was prepared using an automated method with dimethylformamide (DMF) as the solvent in a positron emission tomography (PET)-MF-2 V-IT-I synthesizer. Tracer characteristics were examined both in vitro and in vivo. Micro-PET/computed tomography (CT) was performed to investigate the utility of 18F-AlF-PSMA-NF for imaging PSMA-positive tumours in vivo. 18F-AlF-PSMA-NF was prepared automatically within 35 min with a non-attenuation correction yield of 37.9 ± 11.2%. The tracer was hydrophilic, had a high affinity for PSMA (Kd = 2.58 ± 0.81 nM), and showed stability in both in vitro and in vivo conditions. In the cellular experiments, 18F-AlF-PSMA-NF uptake in PSMA-positive LNCaP cells was significantly higher than that in PSMA-negative PC-3 cells (P < 0.001), and could be blocked by excess ZJ-43—a PSMA inhibitor (P < 0.001). LNCaP tumours were clearly visualized by 18F-AlF-PSMA-NF on micro-PET/CT, with a high level of uptake (13.72 ± 2.01 percent injected dose per gram of tissue [%ID/g]) and high tumour/muscle ratio (close to 50:1). The PSMA-positive LNCaP tumours had a significantly higher uptake than PSMA-negative PC-3 tumours (13.72 ± 2.01%ID/g vs. 1.07 ± 0.48%ID/g, t = 10.382, P < 0.001), and could be blocked by ZJ-43 (13.72 ± 2.01%ID/g vs. 2.77 ± 1.44%ID/g, t = 8.14, P < 0.001). A new 18F-AlF-labelled PSMA probe—18F-AlF-PSMA-NF—was successfully developed and can be prepared automatically. It has the biological characteristics resembling that of a PSMA-based probe and can potentially be used in clinical settings. [ABSTRACT FROM AUTHOR]

[Display omitted] • 18F-FAPTG as a novel radiotracer for FAP PET imaging was developed. • Compared to 18F-FAPI-42, 18F-FAPTG showed significantly lower uptake in gallbladder, with higher tumor uptake and longer tumor retention. • The pilot clinical study demonstrated the safety and feasibility of 18F-FAPTG. Fibroblast activation protein (FAP) is a promising molecular target for imaging in various types of cancers. Several 18F-labeled FAP inhibitor (FAPI) tracers have been evaluated in clinical study. However, these tracers display high physiological uptake in gallbladder and bile duct system. To overcome the limitation, we herein designed a novel radiotracer named 18F-FAPTG. 18F-FAPTG was produced with a non-decay-corrected radiochemical yield of 24.0 ± 6.0% and 22.0 ± 7.0% for manual and automatic synthesis, respectively. 18F-FAPTG exhibited high hydrophilicity and stability in vitro. The studies of cellular uptake, internalization, efflux properties and competitive binding to FAP of 18F-FAPTG indicated that the tracer showed high specificity, rapid internalization and low cellular efflux in FAP-positive cells. Biodistribution studies and microPET in mice bearing FAP-positive xenografts demonstrated extremely low uptake in the majority of other organs and main excretion of 18F-FAPTG through the urinary system. Furthermore, compared to 18F-FAPI-42, 18F-FAPTG showed significantly lower uptake in gallbladder, higher tumor uptake and longer tumor retention. In the pilot clinical study, 18F-FAPTG PET/CT demonstrated favorable tumor-to-background ratios in most organs and clearly displayed the malignant lesions. Our findings indicated that 18F-FAPTG had an advantage over 18F-FAPI-42 in PET imaging for cancers located in gallbladder the bile duct system. Thus, 18F-FAPTG could be an alternative to the currently available FAPI tracers. [ABSTRACT FROM AUTHOR]

The epidermal growth factor receptor (EGFR) has emerged as an attractive target in the treatment of various cancers. Radiolabeled small molecules, antibodies, and peptides that specifically target EGFR are promising probes for tumor imaging to guide personalized treatment with EGFR-targeted drugs. This study aimed to radiolabel GE11 (an EGFR-specific targeting peptide) with 18-fluorine to develop a new EGFR-targeting positron emission tomography (PET) probe, [18F]FP-Lys-GE11, for imaging tumors overexpressing EGFR. [18F]FP-Lys-GE11 was produced by radiolabeling a GE11 peptide with the prosthetic group 4-nitrophenyl-2-[18F]fluoropropionate ([18F]NFP). Stability in PBS and mice serum, affinity for A431 cell line, U87 and PC-3 cells uptake and blocking studies, and biodistribution of [18F]FP-Lys-GE11 were determined. 2 h dynamic and static PET scans of probe for tumor-bearing mice normal and inhibition uptake were performed. [18F]FP-Lys-GE11 was stable in PBS and mice serum. The Kd and Bmax values of probe for A431 were 42.43 ± 3.75 nM and 3383 ± 81.73 CPM, respectively. In cell uptake and blocking experiments, a significant reduction in radioactivity accumulation (over 4-fold) was observed by blocking U87 and PC-3 cells with unlabeled peptide. PET imaging of U87 and PC-3 tumor-bearing mice revealed clear tumor imaging (tumor radioactivity accumulation was 3.48 ± 0.44 and 3.68 ± 0.76%ID/g respectively, tumor-to-muscle ratio was 3.45 ± 0.43 and 3.64 ± 0.76 respectively). Blocking imaging revealed that the U87 tumor uptake was significantly inhibited (2.21 ± 0.41%ID/g). The biodistribution and dynamic PET imaging showed that [18F]FP-Lys-GE11 was mainly excreted by the kidneys and the rest was excreted through the bile and intestines. The current results showed that [18F]FP-Lys-GE11was a good radiolabeled peptide probe for EGFR overexpression tumor's imaging. Unlabelled Image [ABSTRACT FROM AUTHOR]

The asialoglycoprotein receptor (ASGPR) is abundantly expressed on the surface of hepatocytes where it recognizes and endocytoses glycoproteins with galactosyl and N -acetylgalactosamine groups. Given its hepatic distribution, the asialoglycoprotein receptor can be targeted by positron imaging agents to study liver function using PET imaging. In this study, the positron imaging agent 18F]FPGal was designed to specifically target hepatic asialoglycoprotein receptor and its effectiveness was assessed in in vitro and in vivo models. The radiosynthesis of 18F]FPGal required 50 min with total radiochemical yields of 18F]FPGal from 18F]fluoride as 10% (corrected radiochemical yield). The K d of 18F]FPGal to ASGPR in HepG2 cells was 1.99 ± 0.05 mM. Uptake values of 0.55% were observed within 30 min of incubation with HepG2 cells, which could be blocked by 200 mM d (+)-galactose (<0.1%). In vivo biodistribution analysis showed that the liver accumulation of 18F]FPGal at 30 min was 4.47 ± 0.96% ID/g in normal mice compared to 1.33 ± 0.07% ID/g in hepatic fibrotic mice (P < 0.01). Reduced uptake in the hepatic fibrosis mouse models was confirmed through PET/CT images at 30 min. Compared to normal mice, the standard uptake value (SUV) in the hepatic fibrosis mice was significantly lower when assessed through dynamic data collection for 1 h. Therefore, 18F]FPGal is a feasible PET probe that provide insight into ASGPR related liver disease. [ABSTRACT FROM AUTHOR]

[Display omitted] 6-O-[18F]Fluoroethylerlotinib (6-O-[18F]FEE), with a suitable half-life for commercial distribution, may be a good replacement for [11C]erlotinib to identify epidermal growth factor receptor (EGFR) positive tumors with activating mutations to tyrosine kinase inhibitors therapy. In this study, we explored the fully automated synthesis of 6-O-[18F]FEE and investigated its pharmacokinetics in tumor-bearing mice. 6-O-[18F]FEE with high specific activity (28–100 GBq/μmol) and radiochemistry purity (over 99 %) was obtained by two-step reaction and Radio-HPLC separation in PET-MF-2 V-IT-1 automated synthesizer. PET imaging of 6-O-[18F]FEE in HCC827, A431, and U87 tumor-bearing mice with different EGFR expression and mutation was performed. Uptake and blocking of PET imaging indicated that the probe specifically targeted exon 19 deleted EGFR (the quantitative analysis of tumor-to-mouse ratio for HCC827, HCC827 blocking, U87, A431 was 2.58 ± 0.24, 1.20 ± 0.15, 1.18 ± 0.19, and 1.05 ± 0.13 respectively). Dynamic imaging was used to study the pharmacokinetics of the probe in tumor-bearing mice. Logan plot graphical analysis demonstrated late linearity and a high fitting correlation coefficient (0.998), supporting reversible kinetics. According to the Akaike Information Criterion (AIC) rule, the 2-compartment reversible model was more consistent with the metabolic properties of 6-O-[18F]FEE. The automated radiosynthesis and pharmacokinetic analysis will promote clinically transformation of 6-O-[18F]FEE. [ABSTRACT FROM AUTHOR]

miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D) patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function. Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia, improved glucose tolerance and insulin sensitivity. Conversely, miR-155 deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin resistance. In addition, consistent with a positive regulatory role of miR-155 in glucose metabolism, miR-155 positively modulates glucose uptake in all cell types examined, while mice overexpressing miR-155 transgene show enhanced glycolysis, and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at least partially, through miR-155-mediated repression of important negative regulators (i.e. C/EBPβ, HDAC4 and SOCS1) of insulin signaling. Taken together, these findings demonstrate, for the first time, that miR-155 is a positive regulator of insulin sensitivity with potential applications for diabetes treatment. [ABSTRACT FROM AUTHOR]

Abstract: The luminol–CdTe quantum dots (QDs) conjugates were prepared through the reaction between –NH2 and –COOH. The resonance energy transfer between chemiluminescence donor (luminol–H2O2 system) and quantum dots (QDs, with different emission peaks) acceptors (CRET) was investigated. The luminescence of QDs in luminol–QDs conjugates in the process of CRET was influenced by the molar ratio of luminol/QDs. It could reach higher luminescence intensity while the luminol/QDs value was 1/1. Quantum yield of QDs and overlapping areas between the emission spectrum of luminol and adsorption spectrum of QDs played important roles in the CRET efficiency of luminol–QDs conjugates. The higher CRET efficiency (21.2%) was observed when the 540nm QDs were used as acceptors. This work will offer helpful knowledge for the CRET studies based on QDs. [Copyright &y& Elsevier]

Abstract: Introduction: 2-Amino-6-[18F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[18F]FPCV) was prepared via a one-step nucleophilic substitution and evaluated as a novel probe for imaging the expression of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene. Methods: Log P of 6-[18F]FPCV was calculated in octanol/phosphate-buffered saline (PBS). Stability studies were performed in PBS and bovine serum albumin (BSA). Cell uptake was performed at various time points in wild-type cells and transduced cells. For in vivo studies, tumors were grown in nude mice by inoculation with C6 cells, wild type and tk positive. The radiotracer was intravenously injected to animals, and micro-PET imaging was performed. Biodistribution of 6-[18F]FPCV was performed on another group of animals at different time points. Results: Log P of 6-[18F]FPCV was −0.517. 6-[18F]FPCV was fairly stable in PBS and BSA at 6 h. The tracer uptake in C6-tk cells was 5.5–18.8 times higher than that in wild-type cells. The plasma half-life of 6-[18F]FPCV was as follows: α t 1/2=1.2 min and β t 1/2=73.7 min. The average ratio of tumor uptake between the transduced tumor and the wild-type tumor was 1.69 at 15 min. Conclusion: Biological evaluation showed that 6-[18F]FPCV is a potential probe for imaging HSV1-tk gene expression. However, its in vivo defluorination may limit its application in PET imaging of gene expression. [Copyright &y& Elsevier]

• Synthesis of 18F]FEM as a potential novel PET probe for tumor imaging. • 18F]FEM can specifically accumulate at the tumor site of five different tumor models. • 18F]FEM can quickly cross the blood brain barrier (BBB) and quickly fade out. In the 21st century, the incidence and mortality of cancer, one of the most challenging diseases in the world, have rapidly increased. The purpose of this study was to develop 2-(2-18F]fluoroethoxy)ethyl 4-methylbenzenesulfonate (18F]FEM) as a positron emission tomography (PET) agent for tumor imaging. In this study, 18F]FEM was synthesized with a good radiochemical yield (45.4 ± 5.8%), high specific radioactivity (over 25 GBq/μmol), and commendable radiochemical purity (over 99%). The octanol/water partition coefficient of 18F]FEM was 1.44 ± 0.04. The probe demonstrated good stability in vitro (phosphate-buffered saline (PBS) and mouse serum (MS)), and binding specificity to five different tumor cell lines (A549, PC-3, HCC827, U87, and MDA-MB-231). PET imaging of tumor-bearing mice showed that 18F]FEM specifically accumulated at the tumor site of the five different tumor cell lines. The average tumor-to-muscle (T/M) ratio was over 2, and the maximum T/M values reached about 3.5. The biodistribution and dynamic PET imaging showed that most probes were metabolized by the liver, whereas a small part was metabolized by the kidney. Moreover, dynamic brain images and quantitative data showed 18F]FEM can quickly cross the blood brain barrier (BBB) and quickly fade out, thereby suggesting it may be a promising candidate probe for the imaging of brain tumors. The presented results demonstrated that 18F]FEM is a promising probe for tumor PET imaging. [ABSTRACT FROM AUTHOR]