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Objective: The objective of this study is to compare the effectiveness of the Esmarch bandage and exsanguination tourniquet rings (ETRs) in blood evacuation procedures using a controlled intra-subject design involving healthy volunteers., Methods: A total of 20 healthy adult volunteers (12 males, 8 females) were recruited from the community. Participants underwent blood evacuation procedures on both legs, using the Esmarch bandage on one leg and the ETR on the other. The order of the procedures was randomized. Blood evacuation time, overall blood evacuation rate, and calf blood evacuation rate were measured using 99m Tc-labeled red blood cell imaging. Paired t -tests were conducted to compare the effectiveness of the two methods., Results: The ETRs demonstrated a significantly faster blood evacuation time compared to the Esmarch bandage (mean difference = -41.72 s, P  < 0.0001). The overall blood evacuation rate was slightly higher for the ETRs (mean difference = 1.717%), though not statistically significant ( P  = 0.3680). The calf blood evacuation rate was significantly higher for the ETRs (mean difference = 6.86%, P  = 0.0225). No significant discomfort or adverse reactions were reported by any participants., Conclusion: ETRs are more efficient in terms of blood evacuation time and calf blood evacuation rate compared to the Esmarch bandage, without causing significant discomfort or adverse reactions. These findings suggest that ETRs could be a preferable option in clinical settings for blood evacuation procedures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Technological advances in instruments have greatly promoted the development of positron emission tomography (PET) scanners. State-of-the-art PET scanners such as uEXPLORER can collect PET images of significantly higher quality. However, these scanners are not currently available in most local hospitals due to the high cost of manufacturing and maintenance. Our study aims to convert low-quality PET images acquired by common PET scanners into images of comparable quality to those obtained by state-of-the-art scanners without the need for paired low- and high-quality PET images., Methods: In this paper, we proposed an improved CycleGAN (IE-CycleGAN) model for unpaired PET image enhancement. The proposed method is based on CycleGAN, and the correlation coefficient loss and patient-specific prior loss were added to constrain the structure of the generated images. Furthermore, we defined a normalX-to-advanced training strategy to enhance the generalization ability of the network. The proposed method was validated on unpaired uEXPLORER datasets and Biograph Vision local hospital datasets., Results: For the uEXPLORER dataset, the proposed method achieved better results than non-local mean filtering (NLM), block-matching and 3D filtering (BM3D), and deep image prior (DIP), which are comparable to Unet (supervised) and CycleGAN (supervised). For the Biograph Vision local hospital datasets, the proposed method achieved higher contrast-to-noise ratios (CNR) and tumor-to-background SUVmax ratios (TBR) than NLM, BM3D, and DIP. In addition, the proposed method showed higher contrast, SUV max , and TBR than Unet (supervised) and CycleGAN (supervised) when applied to images from different scanners., Conclusion: The proposed unpaired PET image enhancement method outperforms NLM, BM3D, and DIP. Moreover, it performs better than the Unet (supervised) and CycleGAN (supervised) when implemented on local hospital datasets, which demonstrates its excellent generalization ability., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: 'Kimura's disease (KD) is a rare chronic inflammatory disorder of unknown etiology and is difficult to diagnose due to poor clinical presentation and imaging features. Few studies on characteristics of 18 F-FDG PET/CT of KD have been reported. This study aimed to observe the reliable characteristics and usefulness of 18 F-FDG PET/CT for the evaluation of consecutive patients with KD., Methods: The clinical data and 18 F-FDG PET/CT imaging findings of 8 patients with pathologically confirmed KD were reviewed retrospectively. 18 F-FDG PET/CT images were evaluated visually and semiquantitatively by measuring the maximum standardized uptake value (SUV max ). The correlations between clinical data and 18 F-FDG PET/CT features were analyzed by simple linear regression., Results: This study included 7 males and one female ranging in age from 17 to 79 years. The longest diameter of lesions ranged from 0.8 cm to 4.8 cm, and regional or generalized lymphadenopathy was found in all 8 patients with eosinophilia, while subcutaneous masses and salivary gland involvement concurrently were found in 4 patients. 18 F-FDG PET/CT revealed that these involved lesions had high 18 F-FDG uptake with SUV max  > 2.5 (2.6 to 6.3). Moreover, the margin of the lesions was well defined in 6 cases and ill defined in 2 cases, and homogeneous density and 18 F-FDG uptake were both found in all these lesions. There was negative correlation between eosinophils and SUV max (R 2  = 0.538)., Conclusions: Kimura's disease should be considered when 18 F-FDG PET/CT is characterized by homogeneous lesions of regional or generalized lymphadenopathy, accompanied with subcutaneous masses and salivary gland involvement concurrently, especially in patients with eosinophilia., (© 2024. The Author(s).)

Background: Rising prostate-specific antigen (PSA) levels following radical prostatectomy are indicative of a poor prognosis, which may associate with periprostatic adipose tissue (PPAT). Accordingly, we aimed to construct a dynamic online nomogram to predict tumor short-term prognosis based on 18 F-PSMA-1007 PET/CT of PPAT., Methods: Data from 268 prostate cancer (PCa) patients who underwent 18 F-PSMA-1007 PET/CT before prostatectomy were analyzed retrospectively for model construction and validation (training cohort: n = 156; internal validation cohort: n = 65; external validation cohort: n = 47). Radiomics features (RFs) from PET and CT were extracted. Then, the Rad-score was constructed using logistic regression analysis based on the 25 optimal RFs selected through maximal relevance and minimal redundancy, as well as the least absolute shrinkage and selection operator. A nomogram was constructed to predict short-term prognosis which determined by persistent PSA., Results: The Rad-score consisting of 25 RFs showed good discrimination for classifying persistent PSA in all cohorts (all P < 0.05). Based on the logistic analysis, the radiomics-clinical combined model, which contained the optimal RFs and the predictive clinical variables, demonstrated optimal performance at an AUC of 0.85 (95% CI: 0.78-0.91), 0.77 (95% CI: 0.62-0.91) and 0.84 (95% CI: 0.70-0.93) in the training, internal validation and external validation cohorts. In all cohorts, the calibration curve was well-calibrated. Analysis of decision curves revealed greater clinical utility for the radiomics-clinical combined nomogram., Conclusion: The radiomics-clinical combined nomogram serves as a novel tool for preoperative individualized prediction of short-term prognosis among PCa patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To develop an end-to-end radiomics-based pipeline for the prediction of International Society of Urological Pathology grade group (ISUP GG) in prostate cancer (PCa)., Methods: This retrospective study includes 356 patients (241 in training set and 115 in independent test set) with histopathologically confirmed PCa who underwent [ 18 F]PSMA-1007 PET/CT scan. Patients were classified into two groups according to their ISUP GG (1-3 vs. 4-5). Radiomics features were extracted from the whole, automatically segmented prostate on PET/CT images, 30 models were constructed by combining 6 feature selection algorithms and 5 machine learning classifiers. The clinical model incorporated age, total prostate-specific antigen (tPSA), maximum standardized uptake value (SUVmax), and prostate volume. The predictive performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC), balanced accuracy (bAcc), and decision curve analysis (DCA)., Results: The best-performing radiomics model significantly outperformed clinical model (AUC 0.879 ± 0.041 vs. 0.799 ± 0.051, bAcc 0.745 ± 0.074 vs. 0.629 ± 0.045). On an external independent test set, best-performing radiomics model perform better than clinical model, with an AUC of 0.861 vs. 0.750, p = 0.002 (Delong), and bAcc of 0.764 vs. 0.582, p = 0.043 (McNemar). The learning curve, calibration curve and DCA demonstrated goodness-of-fit and improved benefits in clinical practice., Conclusion: The end-to-end radiomics-based pipeline is an effective non-invasive tool to predict ISUP GG in PCa., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Naphthalocyanine-based agents exhibit huge potential in photodynamic therapy, yet their photodynamic performance is restricted by the penetration depth of the external laser. Herein, we employed 18 F-FDG as an internal light source to excite silicon naphthalocyanine nanoparticles to simultaneously circumvent radiative transition and boost 1 O 2 generation for tumor suppression.

The skeleton has been suggested to function as an endocrine organ controlling whole organism energy balance, however the mediators of this effect and their molecular links remain unclear. Here, utilizing Schnurri-3 -/- (Shn3 -/- ) mice with augmented osteoblast activity, we show Shn3 -/- mice display resistance against diet-induced obesity and enhanced white adipose tissue (WAT) browning. Conditional deletion of Shn3 in osteoblasts but not adipocytes recapitulates lean phenotype of Shn3 -/- mice, indicating this phenotype is driven by skeleton. We further demonstrate osteoblasts lacking Shn3 can secrete cytokines to promote WAT browning. Among them, we identify a C-terminal fragment of SLIT2 (SLIT2-C), primarily secreted by osteoblasts, as a Shn3-regulated osteokine that mediates WAT browning. Lastly, AAV-mediated Shn3 silencing phenocopies the lean phenotype and augmented glucose metabolism. Altogether, our findings establish a novel bone-fat signaling axis via SHN3 regulated SLIT2-C production in osteoblasts, offering a potential therapeutic target to address both osteoporosis and metabolic syndrome., (© 2024. The Author(s).)

Cyanine derivatives are organic dyes widely used for optical imaging. However, their potential in longitudinal optoacoustic imaging and photothermal therapy remains limited due to challenges such as poor chemical stability, poor photostability, and low photothermal conversion. In this study, we present a new structural modification for cyanine dyes by introducing a strongly electron-withdrawing group (barbiturate), resulting in a new series of barbiturate-cyanine dyes (BC810, BC885, and BC1010) with suppressed fluorescence and enhanced stability. Furthermore, the introduction of BC1010 into block copolymers (PEG 114 -b-PCL 60 ) induces aggregation-caused quenching, further boosting the photothermal performance. The photophysical properties of nanoparticles (BC1010-NPs) include their remarkably broad absorption range from 900 to 1200 nm for optoacoustic imaging, allowing imaging applications in NIR-I and NIR-II windows. The combined effect of these strategies, including improved photostability, enhanced nonradiative relaxation, and aggregation-caused quenching, enables the detection of optoacoustic signals with high sensitivity and effective photothermal treatment of in vivo tumor models when BC1010-NPs are administered before irradiation with a 1064 nm laser. This research introduces a barbiturate-functionalized cyanine derivative with optimal properties for efficient optoacoustics-guided theranostic applications. This new compound holds significant potential for biomedical use, facilitating advancements in optoacoustic-guided diagnostic and therapeutic approaches., Competing Interests: Declaration of competing interest V.N. is a founder and equity owner of sThesis GmbH, iThera Medical GmbH, Spear UG, and I3 Inc. The remaining authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Lanthanide nanoparticle (LnNP) scintillators exhibit huge potential in achieving radionuclide-activated luminescence (radioluminescence, RL). However, their structure-activity relationship remains largely unexplored. Herein, progressive optimization of LnNP scintillators is presented to unveil their structure-dependent RL property and enhance their RL output efficiency. Benefiting from the favorable host matrix and the luminescence-protective effect of core-shell engineering, NaGdF 4  : 15 %Eu@NaLuF 4 nanoparticle scintillators with tailored structures emerged as the top candidates. Living imaging experiments based on optimal LnNP scintillators validated the feasibility of laser-free continuous RL activated by clinical radiopharmaceuticals for tumor multiplex visualization. This research provides unprecedented insights into the rational design of LnNP scintillators, which would enable efficient energy conversion from Cerenkov luminescence, γ-radiation, and β-electrons into visible photon signals, thus establishing a robust nanotechnology-aided approach for tumor-directed radio-phototheranostics., (© 2024 Wiley-VCH GmbH.)

Abstract: A 33-year-old woman was referred for radioiodine 6 months after total thyroidectomy and neck dissection for papillary thyroid cancer. Posttherapy whole-body 131 I scintigraphy showed not only the known activity in the neck but also accumulated activity in both feet. SPECT/CT revealed focal uptake in bilateral great toenails. On further clinical evaluation and follow-up, the patient was diagnosed as paronychia of the great toenails., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Biochemical recurrence (BCR) following radical prostatectomy (RP) is a significant concern for patients with prostate cancer. Reliable prediction models are needed to identify patients at risk for BCR and facilitate appropriate management. This study aimed to develop and validate a clinical-radiomics model based on preoperative [18 F]PSMA-1007 PET for predicting BCR-free survival (BRFS) in patients who underwent RP for prostate cancer., Materials and Methods: A total of 236 patients with histologically confirmed prostate cancer who underwent RP were retrospectively analyzed. All patients had a preoperative [18 F]PSMA-1007 PET/CT scan. Radiomics features were extracted from the primary tumor region on PET images. A radiomics signature was developed using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The performance of the radiomics signature in predicting BRFS was assessed using Harrell's concordance index (C-index). The clinical-radiomics nomogram was constructed using the radiomics signature and clinical features. The model was externally validated in an independent cohort of 98 patients., Results: The radiomics signature comprised three features and demonstrated a C-index of 0.76 (95% CI: 0.60-0.91) in the training cohort and 0.71 (95% CI: 0.63-0.79) in the validation cohort. The radiomics signature remained an independent predictor of BRFS in multivariable analysis (HR: 2.48, 95% CI: 1.47-4.17, p < 0.001). The clinical-radiomics nomogram significantly improved the prediction performance (C-index: 0.81, 95% CI: 0.66-0.95, p = 0.007) in the training cohort and (C-index: 0.78 95% CI: 0.63-0.89, p < 0.001) in the validation cohort., Conclusion: We developed and validated a novel [18 F]PSMA-1007 PET-based clinical-radiomics model that can predict BRFS following RP in prostate cancer patients. This model may be useful in identifying patients with a higher risk of BCR, thus enabling personalized risk stratification and tailored management strategies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Key Clinical Message: In addition to post-transplant lymphoproliferative disorders, it is necessary to be alert to the drug-resistant bacteria or fungal infection, especially Talaromyces marneffei , in kidney transplant patients who have failed antibiotic treatment and whose PET-CT indicates high metabolic mass in the transplanted kidney with a large number of other organs and lymph nodes., Abstract: Talaromyces marneffei (TM) is a rare pathogenic fungus that primarily affects individuals with compromised immune systems. Post-transplant lymphoproliferative disorders (PTLD) are serious complications that can occur after solid organ and cell transplantation. Both TM infection and PTLD can invade the monocyte-macrophage system and often manifest as extranodal masses. This case report describes a kidney transplant patient who presented with symptoms of frequent, urgent, and painful urination over 6 months. Pulmonary CT scans revealed multiple nodules, and PET-CT demonstrated enlarged lymph nodes in the lungs and the transplanted kidney. The clinical manifestations closely mimicked those of PTLD. The confirmation of TM was achieved through pathogen metagenomic next-generation sequencing and renal biopsy. Unfortunately, despite receiving treatment with antifungal agents, anti-infective therapy, the patient's condition did not respond favorably, ultimately resulting in their unfortunate demise due to COVID-19., Competing Interests: No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Activatable near-infrared (NIR) imaging in the NIR-II range is crucial for deep tissue bioanalyte tracking. However, designing such probes remains challenging due to the limited availability of general chemical strategies. Here, we introduced a foundational platform for activatable probes, using analyte-triggered smart modulation of the π-conjugation system of a NIR-II-emitting rhodamine hybrid. By tuning the nucleophilicity of the ortho-carboxy moiety, we achieved an electronic effect termed "firm-push-to-open and light-push-to-lock," which enables complete spirocyclization of the probe before sensing and allows for efficient zwitterion formation when the light-pushing aniline carbamate trigger is transformed into a firm-pushing aniline. This platform produces dual-modality NIR-II imaging probes with ~50-fold fluorogenic and activatable photoacoustic signals in live mice, surpassing reported probes with generally below 10-fold activatable signals. Demonstrating generality, we successfully designed probes for hydrogen peroxide (H 2 O 2 ) and hydrogen sulfide (H 2 S). We envision a widespread adoption of the chemical platform for designing activatable NIR-II probes across diverse applications.

Objectives: Non-tuberculous mycobacteria (NTM) infection is an increasing health problem due to delaying an effective treatment. However, there are few data on 18 F-FDG PET/CT for evaluating the status of NTM patients. The aim of this study was to investigate the potential value of 18 F-FDG PET/CT in guiding the treatment strategy of NTM patients., Methods: We retrospectively analyzed the cases of 23 NTM patients who underwent 18 F-FDG PET/CT. The clinical data, including immune status and severity of NTM pulmonary disease (NTM-PD), were reviewed. The metabolic parameters of 18 F-FDG included maximum standardized uptake value (SUV max ), SUV max of the most FDG-avid lesion (SUV Top ), SUV Top /SUV max of the liver (SUR Liver ), SUV Top /SUV max of the blood (SUR Blood ), metabolic lesion volume (MLV), and total lesion glycolysis (TLG). The optimal cut-off values of these parameters were determined using receiver operating characteristic curves., Results: There were 6 patients (26.09%) with localized pulmonary diseases and 17 patients (73.91%) with disseminated diseases. The NTM lesions had high or moderate 18 F-FDG uptake (median SUV Top : 8.2 ± 5.7). As for immune status, the median SUV Top in immunocompromised and immunocompetent patients were 5.2 ± 2.5 and 10.0 ± 6.4, respectively, with a significant difference (P = 0.038). As for extent of lesion involvement, SUR Liver and SUR Blood in localized pulmonary and disseminated diseases were 1.9 ± 1.1 vs. 3.8 ± 1.6, and 2.7 ± 1.8 vs. 5.5 ± 2.6, respectively, with a significant difference (P = 0.016 and 0.026). Moreover, for disease severity, SUV max of the lung lesion (SUV I-lung ) and SUV max of the marrow (SUV Marrow ) in the severe group were 7.7 ± 4.3 and 4.4 ± 2.7, respectively, significantly higher than those in the non-severe group (4.4 ± 2.0 and 2.4 ± 0.8, respectively) (P = 0.027 and 0.036). The ROC curves showed that SUV Top , SUR Liver , SUR Blood , SUV I-lung , and SUV Marrow had a high sensitivity and specificity for the identification of immune status, lesion extent, and severity of disease in NTM patients., Conclusion: 18 F-FDG PET/CT is a useful tool in the diagnosis, evaluation of disease activity, immune status, and extent of lesion involvement in NTM patients, and can contribute to planning the appropriate treatment for NTM., (© 2024. The Author(s).)

Accurate diagnosis and staging are crucial for selecting treatment for patients with pancreatic ductal adenocarcinoma (PDAC). The desmoplastic responses associated with PDAC are often characterized by hypometabolism. Here, we investigated 18 F-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in evaluation of PDAC and compared the findings with those obtained using 18 F-FDG. Methods: Sixty-two PDAC patients underwent 18 F-FAPI-04 PET/CT and 18 F-FDG PET/CT. Identification of primary lesions, lymph node (LN) metastasis, and distant metastasis (DM) by these methods was evaluated, and TNM staging was performed. Correlation between SUV max of the primary lesion and treatment response was explored in patients who received systemic therapy. Results: 18 F-FAPI-04 PET/CT identified all patients with PDAC; 18 F-FDG PET/CT missed 1 patient. Tracer uptake was higher in 18 F-FAPI-04 PET/CT than in 18 F-FDG PET/CT in primary tumors (10.63 vs. 2.87, P < 0.0001), LN metastasis (2.90 vs. 1.43, P < 0.0001), and DM (liver, 6.11 vs. 3.10, P = 0.002; peritoneal, 4.70 vs. 2.08, P = 0.015). The methods showed no significant difference in the T staging category, but the N and M values were significantly higher for 18 F-FAPI-04 PET/CT than for 18 F-FDG PET/CT ( P = 0.002 and 0.008, respectively). Thus, 14 patients were upgraded, and only 1 patient was downgraded, by 18 F-FAPI-04 PET/CT compared with 18 F-FDG PET/CT. A high SUV max of the primary tumor did not correlate with treatment response for either 18 F-FAPI-04 or 18 F-FDG. Conclusion: 18 F-FAPI-04 PET/CT performed better than 18 F-FDG PET/CT in identification of primary tumors, LN metastasis, and DM and in TNM staging of PDAC., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses., (© The Author(s) 2024. Published by Oxford University Press.)

Radionuclides internal radiotherapy (RIT) is a clinically powerful method for cancer treatment, but still poses unsatisfactory therapeutic outcomes due to the hypoxic characteristic of tumor microenvironment (TME). Catalase (CAT) or CAT-like nanomaterials can be used to enzymatically decompose TME endogenous H 2 O 2 to boost TME oxygenation and thus alleviate the hypoxic level within tumors, but their effectiveness is still hindered by the short-lasting of hypoxia relief owing to their poor stability or degradability, thereby failing to match the long therapeutic duration of RIT. Herein, we proposed an innovative strategy of using facet-dependent CAT-like Pd-based two-dimensional (2D) nanoplatforms to continuously enhance RIT. Specifically, rationally designed 2D Pd@Au nanosheets (NSs) enable consistent enzymatic conversion of endogenous H 2 O 2 into O 2 to overcome hypoxia-induced RIT resistance. Furthermore, partially coated Au layer afford NIR-II responsiveness and moderate photothermal treatment that augmenting their enzymatic functionality. This approach with dual-effect paves the way for reshaping TME and consequently facilitating the brachytherapy ablation of cancer. Our work offers a significant advancement in the integration of catalytic nanomedicine and nuclear medicine, with the overarching goal of amplifying the clinical benefits of RIT-treated patients., (© 2023. The Author(s).)

Background: Lymphomas involving the gastrointestinal tract may be manifested as anti-inflammatory tract bleeding, abdominal lymph node enlargement, or even perforation of the gastrointestinal tract. After organ transplantation, the likelihood of post-transplant lymphoproliferative disorders increases, and some rare infections may also appear., Case Presentation: Herein, we report a living transplant patient with talaromycosis marneffei (TSM) or Talaromyces marneffei (TM) infection with gastrointestinal hemorrhage and systemic lymph node enlargement, which presented clinically as lymphoma., Conclusion: This case is TSM in a kidney transplant patient, confirmed by lymph node biopsy and blood culture. The patient discharged from hospital successfully under the treatment of antifungal therapy and immunosuppressive therapy. Physicians should be aware that TSM can mimic lymphoma, and early diagnosis and treatment can benefit the outcomes., (© 2023. The Author(s).)

Background: Fibroblast activation protein (FAP) has shown high expression in inflammatory responses and fibrosis., Hypothesis: We speculated that FAP could serve as a diagnostic and monitoring target in the tendon healing process., Study Design: Controlled laboratory study., Methods: A total of 72 Sprague-Dawley rats were randomly divided into a tendon crush group and a half-partial tendon laceration group. Four rats in each group were injected with radiotracers weekly for 4 weeks after surgery, with aluminum fluoride-labeled 1,4,7-triazacyclononane-N,N',N″-triacetic acid-conjugated FAP inhibitor (Al 18 F-NODA-FAPI-04) administered on the first day of each week and 18 F-fludeoxyglucose ( 18 F-FDG) on the next day. Small animal positron emission tomography (PET) imaging was performed, and tendon tissue was collected for pathology and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis each week after surgery., Results: One week after surgery, both radiotracers showed signal concentration at the lesion site, which was the highest radioactive uptake observed during 4 weeks postoperatively, consistent with the severity of the lesion. Consistent trends were observed for inflammatory cytokines during qRT-PCR analysis. Additionally, Al 18 F-NODA-FAPI-04 PET exhibited a more precise lesion pattern, attributed to its high specificity for naive fibroblasts when referring to histological findings. Over time, the uptake of both radiotracers at the injury site gradually decreased, with 18 F-FDG experiencing a more rapid decrease than Al 18 F-NODA-FAPI-04. In the fourth week after surgery, the maximum standardized uptake values of Al 18 F-NODA-FAPI-04 in the injured lesion almost reverted to the baseline levels, indicating a substantial decrease in naive fibroblasts and inflammatory cells and a reduction in inflammation and fibrosis, especially compared with the first week. Corresponding trends were also revealed in pathological and qRT-PCR results., Conclusion: Our findings suggest that inflammation is a prominent feature during the early stage of tendon injury. Al 18 F-NODA-FAPI-04 PET allows accurate localization and provides detailed morphological imaging, enabling continuous monitoring of the healing progress and assessment of injury severity., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was funded by the National Natural Science Foundation of China (grant No. 81702135), Zhejiang Provincial Natural Science Foundation (grant No. LTGY23H180014), and the Zhejiang Traditional Chinese Medicine Research Program (grant No. 2017ZB057). These funding bodies had no role in the design of the study, in the collection, analysis, and interpretation of data, and in drafting the manuscript. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Abstract: A 41-year-old woman with right papillary thyroid carcinoma underwent 131 I therapy (3.7 GBq). Posttherapy whole-body scintigraphy acquired 2 days later revealed a focus of intense activity in the anterior aspect of the left knee. The activity corresponding to the posttraumatic scab. Posttraumatic scab should be considerable a cause of false-positive whole-body scintigraphy findings., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Cerenkov radiation from radiopharmaceuticals (18F-FDG) serves as an internal light source to excite UV-responsive silicon nanocrystals for near-infrared luminescence imaging that offers deeper tissue penetration and high signal-to-noise ratio.

Background: Parathyroid carcinoma and parathyromatosis are very rare diseases in patients on hemodialysis. Its pathogenesis, clinical features, preoperative diagnosis, and surgery are challenging. We describe a rare case of recurrent hyperparathyroidism due to synchronous parathyroid carcinoma and parathyromatosis., Case Presentation: A 46-year-old Chinese woman was diagnosed with end-stage renal disease and received regular hemodialysis. Four years later, she experienced discomfort due to itching and was diagnosed with drug-resistant secondary hyperparathyroidism. Parathyroidectomy was performed, and her parathyroid hormone (PTH) levels were reduced. The pathology also revealed that the four nodules were parathyroid nodular hyperplasia without evidence of malignancy. Five years after surgery, the right subcutaneous nodule and left inferior nodule were detected by multiple imaging modalities, and the nodules were accompanied by recurrence itching and elevation of PHT. A complete resection of two nodules was performed, and the patient was diagnosed with parathyroid carcinoma and parathyromatosis. At 8 months postsurgery, her PHT and serum calcium levels were stable, and there were no signs of recurrence., Conclusions: This is a rare case of synchronous parathyroid carcinoma and parathyromatosis in a patient with secondary hyperparathyroidism after parathyroidectomy. We suggest meticulous handling of parathyroid hyperplasia to avoid rupture and spillage during surgery, and precise pro-operation location by multiple imaging modalities is crucial for successful parathyroidectomy., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Alzheimer's disease (AD) is the most prevalent form of dementia among elderly people worldwide. Cerebrospinal fluid (CSF) is the optimal fluid source for AD biomarkers, while serum biomarkers are much more achievable. To search for novel diagnostic AD biomarkers, we performed a quantitative proteomic analysis of CSF and serum samples from AD and normal cognitive controls (NC). CSF and serum proteomes were analyzed via data-independent acquisition quantitative mass spectrometry. Our bioinformatic analysis was based on Gene Ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. In comparison to the controls, 8 proteins were more abundant in AD CSF, and 60 were less abundant in AD CSF, whereas 55 proteins were more and 10 were less abundant in the serum samples. ATPase-associated activity for CSF and mitochondrial functions for CSF and serum were the most enriched GO terms of the DEPs. KEGG enrichment analysis showed that the most significant pathways for the differentially expressed proteins were the N-glycan biosynthesis pathways. The area under the curve (AUC) values for CSF sodium-/potassium-transporting ATPase subunit beta-1 (AT1B1), serglycin (SRGN), and thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) were 0.867 ( p = 0.004), 0.833 ( p = 0.008), and 0.783 ( p = 0.025), respectively. A panel of the above three CSF proteins accurately differentiated AD (AUC = 0.933, p = 0.001) from NC. The AUC values for serum probable phospholipid-transporting ATPase IM (AT8B4) and SRGN were moderate. The AUC of the CSF SRGN + serum SRGN was 0.842 ( p = 0.007). These novel AD biomarker candidates are mainly associated with inflammation, ATPase activity, oxidative stress, and mitochondrial dysfunction. Further studies are needed to investigate the molecular mechanisms by which these potential biomarkers are involved in AD.

Objectives: Gallium-68 ( 68 Ga)-labeled somatostatin analog (SSA) PET imaging has been widely used in clinical practice of neuroendocrine neoplasms (NENs). Compared with 68 Ga, 18 F has a great practical and economic advantage. Although a few studies have shown the characteristics of [ 18 F] AlF-NOTA-octreotide ([ 18 F]-OC) in healthy volunteers and small NEN patient groups, its clinical value needs further investigation. Herein, this retrospective study aimed to evaluate the diagnostic accuracy of [ 18 F]-OC PET/CT in detecting NENs, as well as to compare it with contrast-enhanced CT/MRI., Methods: We retrospectively reviewed the data of 93 patients who had undergone [ 18 F]-OC PET/CT and CT or MRI scans. Of these patients, there were 45 patients with suspected NENs for diagnostic evaluation, and 48 patients with pathologically confirmed NENs for detecting metastasis or recurrence. [ 18 F]-OC PET/CT images were evaluated visually and semi-quantitatively by measuring maximum standardized uptake value of tumor (SUV max ), tumor-to-background SUV max ratio (TBR), and SUV max of hypophysis (SUV hypophysis ). A total of 276 suspected NEN lesions were found in these 93 patients. The results of histopathology or radiographic follow-up served as the reference standard for the final diagnosis., Results: Forty-five patients with suspected NENs were confirmed by histopathological examination via resection or biopsy. [ 18 F]-OC PET/CT showed high radiotracer uptake in the lesions of G1-G3 NENs. [ 18 F]-OC PET/CT showed superior performance with 96.3% of sensitivity, 77.8% of specificity, and 88.9% of accuracy in diagnosing NENs compared to CT/MRI. When cutoffs of SUV max , TBR, and SUV hypophysis were 8.3, 3.1, and 15.4, [ 18 F]-OC PET/CT had the best equilibrium between sensitivity and specificity for differentiating NEN from non-NEN lesions. For a total of 276 suspected NEN lesions, the sensitivity, specificity, and accuracy of [ 18 F]-OC PET/CT for diagnosis of NENs were 90.5%, 82.1%, and 88.8%, respectively, and were higher than those of CT and MRI. G1 and G2 NENs had higher TBR and lower CT enhancement intensity than G3. The SUV max and TBR had a positive correlation with CT enhancement intensity in G2 rather than in G1 or G3., Conclusions: [ 18 F]-OC PET/CT is a promising imaging modality for initial diagnosis and detecting metastasis or postoperative recurrence in NENs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Acute kidney injury (AKI) is a common clinical syndrome lacking effective pharmacotherapy. Gambogic acid (GA), as an active ingredient of herbal medicines, exhibits antioxidant and anti-inflammatory effects that benefit the treatment of AKI, but its poor aqueous solubility limits effective renal delivery. We, for the first time, developed GA-based nanoparticles (GA-NPs) with preferential renal uptake for AKI treatment. By PEGylating with NH 2 -PEG5000-NOTA, hydrophobic GA was self-assembled into ∼4.5 nm nanoparticles, which showed the enhanced renal accumulation in AKI models from PET images. Importantly, the in vitro cell assays and in vivo tests of the two AKI models have confirmed the obvious nephroprotective effects and biosafety of GA-NPs. Therefore, this work indicates that GA-NPs can be a promising therapeutic candidate for the management of AKI.

Benzamide (BZA), a small molecule that can freely cross cell membranes and bind to melanin, has served as an effective targeting group for melanoma theranostics. In this study, a novel pyridine-based BZA dimer (denoted as H-2) was labeled with 68 Ga ([ 68 Ga]Ga-H-2) for positron emission tomography (PET) imaging of malignant melanomas. [ 68 Ga]Ga-H-2 was obtained with high radiochemical yield (98.0 ± 2.0%) and satisfactory radiochemical purity (>95.0%). The specificity and affinity of [ 68 Ga]Ga-H-2 were confirmed in melanoma B16F10 cells and in vivo PET imaging of multiple tumor models (B16F10 tumors, A375 melanoma, and lung metastases). Monomeric [ 68 Ga]Ga-H-1 was prepared as a control radiotracer to verify the effects of the molecular structure on pharmacokinetics. The values of the lipid-water partition coefficient of [ 68 Ga]Ga-H-2 and [ 68 Ga]Ga-H-1 demonstrated hydrophilicity with log P = -2.37 ± 0.07 and -2.02 ± 0.09, respectively. PET imaging and biodistribution showed a higher uptake of [ 68 Ga]Ga-H-2 in B16F10 primary and metastatic melanomas than that in A375 melanomas. However, the relatively low uptake of monomeric [ 68 Ga]Ga-H-1 in B16F10 tumors and high accumulation in nontarget organs resulted in poor PET imaging quality. This study demonstrates the synthesis and preclinical evaluation of the novel pyridine-based BZA dimer [ 68 Ga]Ga-H-2 and indicates that the dimer tracer has promising applications in malignant melanoma-specific PET imaging because of its high uptake and long-time retention in malignant melanoma.

Microbicides with distinct antibacterial mechanisms show potential to combat multi-drug resistance bacteria. We herein report peptidoglycan-directed chemical ligation (PGCL) between alkyne-bearing vancomycin and an azide-tagged cationic polymer. The former binds peptidoglycan and inhibits peptidoglycan crosslinking, while the latter interferes the integrity of the bacterial membrane. PGCL results in enhanced bactericidal activity against Gram-positive Staphylococcus aureus ( S. aureus ) over Gram-negative Escherichia coli ( E. coli ). These data indicate the potential of PGCL to selectively and synergistically inhibit Gram-positive pathogens via dual modality antibacterial mechanisms of peptidoglycan-inhibiting antibiotics and bacterial membrane-disrupting polycations., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Macrophages have crucial roles in the pathogenesis of rheumatoid arthritis (RA). We aimed to elucidate the temporal profile of macrophage infiltration in synovitis in RA rat models using PET (positron emission tomography) imaging based a new generation of TSPO (Translocator protein, 18 kDa)-PET ligand, 18 F-VUIIS1008 {2-[5,7-Diethyl-2-{4-[2-( 18 F)fluoroethoxy]phenyl}pyrazolo(1,5-a)pyri-midin-3-yl]-N, N-diethylacetamide}. In vitro and in vivo studies were conducted using RAW264.7 macrophage cells and a rat model of RA induced by Complete Freund's Adjuvant (CFA). Our results showed 18 F-VUIIS1008 showed excellent stability in vitro and binding specificity to RAW264.7 cells, and rapid accumulation in the left inflammatory ankles. PET studies revealed that 18 F-VUIIS1008 could clearly identify the left inflammatory ankles with good contrast at 30-120 min post-injection. The uptake of 18 F-VUIIS1008 of left inflammatory ankles was a wiggle trace with two peaks on day 7 and 29, and then, the highest peak uptake was seen on day 29 (3.00% ± 0.08%ID/g) at 60 min after injection. Tracer uptakes could be inhibited by PK11195 or VUIIS1008. Immunohistochemistry and immunofluorescence tests showed that elevated TSPO expression and infiltrated macrophages were found in the left inflammation ankles. 18 F-VUIIS1008 as a novel PET imaging agent showed great potential to identify temporal profile of macrophage infiltration in synovitis in RA, and deliver accurate non-invasive diagnosis and real-time monitoring of RA development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Su, Wang, Yang and Guo.)

Cerenkov radiation (CR) from radionuclides and megavoltage X-ray radiation can act as an in situ light source for deep cancer theranostics, overcoming the limitations of external light sources. Despite the blue-weighted emission and low quantum yield of CR, activatable probes-mediated CR can enhance the in-vivo diagnostic signals by Cerenkov resonance energy transfer and also can produce therapeutic effects by reactive species generation/drug release, greatly promoting the biomedical applications of CR. In this review, we describe the principles and sources of CR, construction of CR-activated probes and their application to tumor optical imaging and therapy. Finally, future prospects for the design and biomedical application of CR-activated probes are discussed., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: It is vital to distinguish between inflammatory and malignant lymphadenopathy in human immunodeficiency virus (HIV) infected individuals. The purpose of our study was to differentiate the variations in the clinical characteristics of HIV patients, and apply 18 F-FDG PET/CT parameters for distinguishing of malignant lymphoma and inflammatory lymphadenopathy in such patients., Methods: This retrospective cross-sectional study included 59 consecutive HIV-infected patients who underwent whole-body 18 F-FDG PET/CT. Of these patients, 37 had biopsy-proven HIV-associated lymphoma, and 22 with HIV-associated inflammatory lymphadenopathy were used as controls. The determined parameters were the maximum of standard uptake value (SUV max ), SUV max of only lymph nodes (SUV LN ), the most FDG-avid lesion-to-liver SUV max ratio (SUR max ), laboratory examinations and demographics. The optimal cut-off of 18 F-FDG PET/CT value was analyzed by receiver operating characteristic curve (ROC)., Results: Considering the clinical records, the Karnofsky Performance Status (KPS) scores in patients with inflammatory lymphadenopathy were obviously higher than those in patients with malignant lymphoma (P = 0.015), whereas lymphocyte counts and lactate dehydrogenase (LDH) were obviously lower (P = 0.014 and 0.010, respectively). For the 18 F-FDG PET/CT imaging, extra-lymphatic lesions, especially digestive tract and Waldeyer's ring, occurred more frequently in malignant lymphoma than inflammatory lymphadenopathy. Furthermore, the SUR max and SUV LN in malignant lymphoma were markedly higher than those in inflammatory lymphadenopathy (P = 0.000 and 0.000, respectively). The cut-off point of 3.1 for SUR max had higher specificity (91.9%) and relatively reasonable sensitivity (68.2%) and the cut-off point of 8.0 for the SUV LN had high specificity (89.2%) and relatively reasonable sensitivity (63.6%)., Conclusion: Our study identified the distinctive characteristics of the clinical manifestations, the SUR max , SUV LN and detectability of extra-lymphatic lesions on 18 F-FDG PET, and thus provides a new basis for distinguishing of malignant lymphoma from inflammatory lymphadenopathy in HIV-infected patients., (© 2022. The Author(s).)

Lysosomal rupture engaged in diverse diseases remains poorly discerned from lysosomal membrane permeabilization (LMP). We herein reported biocapture-directed chemical labeling (BCCL) for the discern of lysosomal rupture by tracking the release of optically labeled cathepsins from damaged lysosomes into the cytosol. BCCL entails covalent anchoring of an azide-tagged suicide substrate (Epo-LeuTyr Az ) to the enzyme active site and bioorthogonal ligation of the introduced azide with DBCO RC, a ratiometric sensor featuring an acidity-reporting red emissive X-rhodamine-lactam (ROX), blue emissive coumarin (CM) inert to pH, and DBCO reactive to azide. Aided with fluorescein isocyanate-labeled sialic acid (FITC-Sia), a probe remained in pH-elevated lysosomes but dissipated from LMP + lysosomes, BCCL enables optical discern of four states of lysosomes: ruptured lysosomes (blue in cytosol), LMP + lysosomes (blue in lysosomes), pH-elevated lysosomes (blue and green in lysosomes), and physiological lysosomes (blue, green and red in lysosomes). This approach could find applicability to study lysosome rupture over LMP in diseases and to evaluate lysosome rupture-inducing drugs.

Background: Idiopathic inflammatory myopathy (IIM) is a group of autoimmune diseases that frequently leads to unfavorable outcome. This study aimed at identifying the clinical value of PET/CT scan in predicting the outcome of adult IIM patients., Methods: Adult IIM patients who were admitted to the four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZJU), from January 1, 2017, to December 31, 2020, were retrospectively reviewed. PET/CT scan and other factors of IIM patients who met the inclusion and exclusion criteria were collected and analyzed., Results: A total of 69 adult IIM patients were finally enrolled into this study. Thirty cases (43.5%) of all the patients enrolled died in follow-up, and the medium follow-up time was 11.90 (4.00, 23.80) months. In particular, 14 patients died within 3 months. The univariate Cox proportional hazards regression analyses revealed pulmonary bacterial infection (P < 0.001), rapidly progressive interstitial lung disease (RP-ILD, P = 0.018), maximum standard uptake value of spleen (spleen SUVmax, P = 0.002), and positivity of anti-MDA5 antibody (P = 0.041) were significantly related to survival in follow-up. The following multivariate Cox proportional hazards regression analysis identified pulmonary bacterial infection (P = 0.003) and spleen SUVmax (P = 0.032) as factors significantly associated with survival of IIM-ILD patients. The subsequent receiver operating characteristic curve analysis showed SUVmax was comparably effective in predicting death within 3 months., Conclusion: Spleen SUVmax and complication of pulmonary bacterial infection were significantly associated with survival of IIM patients. In addition, elevated spleen SUVmax was efficient in predicting unfavorable outcome of adult IIM patients. Key Points • IIM is a group of autoimmune diseases that frequently leads to unfavorable outcome • Complications of splenic SUVmax and pulmonary bacterial infection were significantly associated with survival in IIM patients., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: Blood-brain barrier (BBB) is frequently disrupted in patients with diabetes mellitus (DM) and/or neurosyphilis (NS). Clinical cases reflect a trend that non-neurosyphilis (non-NS) patients with impaired glucose tolerance (IGT) are likely to develop NS and/or DM., Objective: To investigate whether IGT promotes BBB disruption in patients with non-NS., Methods and Material: A total of 21 subjects were enrolled, including six with IGT, nine with non-NS, and six with both IGT and non-NS. BBB permeability was evaluated by dynamic contrast-enhanced (DCE) MRI and the secretion of biomarkers from cerebrospinal fluid (CSF) were measured by colorimetric method, immune turbidimetric method, and enzyme-linked immunosorbent assay (ELISA) method., Results: The non-NS patients with IGT have higher BBB permeability at cortex superior frontal gyrus, white matter, and thalamus than non-NS patients without IGT or IGT patients without non-NS. The CSF-serum albumin-quotient (Qalb) levels and CSF secretion are highest in non-NS patients with IGT, including matrix metalloproteinase 9 (MMP9), soluble intercellular cell adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1)., Conclusions: Significant correlations between CSF biomarkers and BBB permeability were found., Competing Interests: None

Objective: Fluorine-18-2-(3-{1-carboxy-5-[(6- 18 F-flfluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid ( 18 F-DCFPyL), a novel positron emission tomography/computed tomography (PET/CT) radiotracer that binds to the prostate specific membrane antigen (PSMA), is increasingly used for biochemically recurrent prostate cancer diagnostics. However, the 18 F-DCFPyL characteristics of suspected prostate cancer (SPCa) have been even more rarely described. Herein, in this retrospective study, we describe the clinical impact of 18 F-DCFPyL PET/CT imaging in SPCa., Subjects and Methods: We retrospectively evaluated the data of 56 SPCa patients who had undergone 18 F-DCFPyL PET/CT studies. These patients were done for primary diagnosis/staging. Positron emission tomography/CT images were analyzed both qualitatively and quantitatively (maximum standardized uptake value (SUVmax) and maximum SUV normalized by lean body mass (SULmax)). Histopathologic diagnosis was taken as reference standard. The optimal cut-off of 18 F-DCFPyL was determined using receiver operating characteristic curve (ROC)., Results: All the patients were confirmed by histopathological examination via prostatectomy or prostate biopsy. Fluorine-18-DCFPyL PET/CT showed higher radiotracer uptake in prostate cancer than that in non-prostate cancer. When SUVmax 5.0 and SULmax 4.0 were cut-off points for determining prostate cancer, the sensitivity of 18 F-DCFPyL was 90%, specificity was 100%, and accuracy was 91.2%. Furthermore, there were highly significant positive correlations between SUVmax, SULmax and serum PSA. On comparison of areas under the curve, no significant difference was seen between SUVmax and SULmax in the sensitivity and specificity of 18 F-DCFPyL PET/CT for PCa identification. However, delayed PET/CT did not improved accuracy in the term of uncertain PCa in the initial standard imaging. As for lymph node staging, the negative predictive value of 18 F-DCFPyL PET/CT was 100%., Conclusion: Fluorine-18-DCFPyL PET/CT is a promising imaging modality for initial diagnosis and preoperative N staging in SPCa.

Approaches that could enable precise photodynamic therapy (PDT) are of therapeutic potential. We herein report a trifunctional probe (Glu-RdEB) that could be activated to generate fluorescent rhodamine species to pinpoint tumor foci. The probe contains a γ-glutaminyl moiety cleavable to γ-glutamyl transpeptidase (GGT) overexpressed in multiple tumors, an entity of an ENBS photosensitizer for PDT, and an entity of rhodamine fluorescently quenched by ENBS. Upon activation by tumor-associated GGT, the probe releases highly fluorescent rhodamine that is selectively confined in tumors whereby light irradiation leads to effective tumor regression in mice. These results indicate the feasibility of a fluorescently quenched dye-photosensitizer pair to yield tumor-activatable fluorescence to direct PDT.

The overexpression of HIF-1α in solid tumors due to hypoxia is closely related to drug resistance and consequent treatment failure. Herein, we constructed a hypoxia-activated prodrug named as YC-Dox. This prodrug could be activated under hypoxic conditions and undergo self-immolation to release doxorubicin (Dox) and YC-1 hemisuccinate (YCH-1), which could execute chemotherapy and result in HIF-1α downregulation, respectively. This prodrug is capable of specifically releasing Dox and YCH-1 in response to hypoxia, leading to a substantial synergistic potency and a remarkable cytotoxic selectivity (>8-fold) for hypoxic cancer cells over normoxic healthy cells. The in vivo experiments reveal that this prodrug can selectively aim at hypoxic cancer cells and avoid undesired targeting of normal cells, leading to elevated therapeutic efficacy for tumor treatment and minimized adverse effects on normal tissues.

Photodynamic therapy (PDT) necessitates approaches capable of increasing antitumor effects while decreasing nonspecific photodamage. We herein report an activatable probe (Glu-PyEB) comprising two distinct photosensitizers with mutually suppressed photodynamics. Activation by tumor-associated γ-glutamyltranspeptidase gives rise to a generator of superoxide radical (O 2 -• ) accumulated in lysosomes and a producer of singlet oxygen ( 1 O 2 ) enriched in mitochondria. This enables light-irradiation-triggered damage of lysosomes and mitochondria, robust cell death, and tumor retardation in vivo, showing the use of paired photosensitizers subjected to reciprocally suppressed photodynamics for activatable PDT.

Radionuclide with Cerenkov radiation (CR) can serve as an internal excitation source to activate photosensitizers for photodynamic therapy (PDT) in deep tumor. However, the low efficiency of CR limits its therapeutic efficacy. A 131 I labeled zinc tetra(4-carboxyphenoxy) phthalocyaninate (ZnPcC4) conjugated Cr 3+ -doped zinc gallate (ZnGa 2 O 4 :Cr 3+ , ZGCs) nanoplatform ( 131 I-ZGCs-ZnPcC4) is developed for radiotherapy (RT) and radiation-induced PDT. 131 I can not only activate ZGCs for long-lasting luminescence via both Cerenkov luminescence (CL) and ionizing radiation, which further continuously activate photosensitizer ZnPcC4 for PDT, but also can directly kill cancerous cells. This 131 I-ZGCs-ZnPcC4 exhibits excellent tumor inhibition both in vitro and in vivo. Combining self-activated PDT and RT, it is believed that the 131 I-ZGCs-ZnPcC4 can greatly benefit the deep tumor therapy., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The aim of this study was to develop a 1-(2-(2-(2-(1,2,3-triazol)ethoxy)ethoxy)ethyl)-5-[ 125/131 I]iodo-1,2,3-triazole-diestradiol ([ 125/131 I]ITE2), for estrogen receptor (ER)-expressing breast cancer imaging with single-photon emission computed tomography (SPECT). [ 125/131 I]ITE2 was prepared in good radiochemical yield (94.4 ± 0.4%) with high radiochemical purity (>99%). [ 125/131 I]ITE2 had good stability in vitro and moderate molar activity (0.3 ± 0.2 GBq/µmol). Higher uptake in ER-positive MCF-7 cells than that of ER-negative MDA-MB-231 cells was observed at all time points. Rats biodistribution showed that [ 131 I]ITE2 had high uptake in ER-abundant uterine and ovarian (5.7 ± 0.4 and 10.1 ± 1.4%ID/g at 1 hr postinjection) and could be blocked by co-injection of estradiol (2.7 ± 0.1 and 5.5 ± 0.4%ID/g) obviously. In the SPECT/CT imaging study, [ 125 I]ITE2 showed significant higher uptake in MCF-7 tumor (3.1 ± 0.4%ID/g) than that of MDA-MB-231 (0.9 ± 0.1%ID/g). Furthermore, the specific uptake of [ 125 I]ITE2 in ER-positive MCF-7 tumor could be blocked effectively by preadministration of fulvestrant (1.2 ± 0.4%ID/g). A novel radioiodinated dimeric estrogen was designed and synthesized with promising ER targeting ability and specificity. It is worthy of further investigation to validate the advantages of the dimer in ER-positive breast cancer diagnosis., (© 2020 John Wiley & Sons A/S.)

Early diagnosis and therapy are crucial to control disease progression optimally and achieve a good prognosis in rheumatoid arthritis (RA). Previous study showed that a technetium-99m ( 99m Tc)-labeled TSPO ligand ( 99m Tc-CB256 [2-(8-(2-(bis(pyridin-2-yl)methyl)amino)acetamido)-2-(4-chlorophenyl) H -imidazo[1,2- a ]pyridin-3-yl)- N , N -dipropylacetamide] composed of a translocator protein (TSPO) ligand CB86 [[2-(4-chlorophenyl)-8-amino-imidazo[1,2- a ]-pyridin-3-yl]- N , N -di- n -propylacetamide] and di-(2-picolyl)amine, a bifunctional chelate agent, was used to image a TSPO-rich cancer cell in vitro ; however, few 99m Tc-CB256 in vivo evaluation has been reported so far probably due to the cytotoxicity of CB256 ( ca . 75 times more than analogous CB86). Herein, we describe a novel TSPO targeting radiopharmaceutical consisting of CB86 and diethylenetriaminepentaacetic acid (DTPA), a conventional bifunctional chelating ligand in clinical trials used to prepare 99m Tc-labeled CB86, and its evaluation as a 99m Tc-single-photon emission computed tomography (SPECT) probe. The radiosynthesis and characterization of 99m Tc-DPTA-CB86 including hydrophilicity and stability tests were determined. Additionally, the binding affinity and specificity of 99m Tc-DTPA-CB86 to TSPO were evaluated using RAW264.7 macrophage cells. Biodistribution and 99m Tc-SPECT studies were conducted on rheumatoid arthritis (RA) rat models after the injection of 99m Tc-DTPA-CB86 with or without co-injection of unlabeled DTPA-CB86. The radiosynthesis of 99m Tc-DTPA-CB86 was completed successfully with the labeling yields and radiochemical purity of 95.86 ± 2.45 and 97.45 ± 0.69%, respectively. The probe displayed good stability in vitro and binding specificity to RAW264.7 macrophage cells. In the biodistribution studies, 99m Tc-DTPA-CB86 exhibited rapid inflammatory ankle accumulation. At 180 min after administration, 99m Tc-DTPA-CB86 uptakes of the left inflammatory ankle were 2.35 ± 0.10 percentage of the injected radioactivity per gram of tissue (% ID/g), significantly higher than those of the normal tissues. 99m Tc-SPECT imaging studies revealed that 99m Tc-DTPA-CB86 could clearly identify the left inflammatory ankle with good contrast at 30-180 min after injection. Therefore, 99m Tc-DTPA-CB86 may be a promising probe for arthritis 99m Tc-SPECT imaging., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Current tumor imaging agents are often limited by their liability to dissipate from tumor tissues. As cell sugar sorting enables exogenous sugars to be delivered into predetermined subcellular locations, we synthesized sialic acid (Sia) derivatives with rhodamine-X conjugated at C-9 ( ROX Sia), which hitchhikes cell sialic acid sorting to target tumor cell lysosomes, exhibiting pH-independent long-term probe retention in lysosomes. ROX Sia gives selective, bright, and endured fluorescence signals in subcutaneous tumors and orthotopic tumors in mice models. These results indicate the potential of ROX Sia as a lysosome-targeted optical agent for fluorescence-guided tumor resection., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Persistent luminescence nanoparticles (PLNPs) with rechargeable near-infrared afterglow properties attract much attention for tumor diagnosis in living animals since they can avoid tissue autofluorescence and greatly improve the signal-to-background ratio. Using UV, visible light, or X-ray as excitation sources to power up persistent luminescence (PL) faces the challenges such as limited tissue penetration, inefficient charging capability, or tissue damage caused by irradiation. Here, it is proved that radiopharmaceuticals can efficiently excite ZnGa 2 O 4 :Cr 3+ nanoparticles (ZGCs) for both fluorescence and afterglow luminescence via Cerenkov resonance energy transfer as well as ionizing radiation. 18 F-FDG, a clinically approved tumor-imaging radiopharmaceutical with a short decay half-life around 110 min, is successfully used as the internal light source to in vivo excite intravenously injected ZGCs for tumor luminescence imaging over 3 h. The luminescence with similar decay time can be re-obtained for multiple times upon injection of 18 F-FDG at any time needed with no health concern. It is believed this strategy can not only provide tumor luminescence imaging with high sensitivity, high contrast, and long decay time at desired time, but also guarantee the patients much less radiation exposure, greatly benefiting image-guided surgery in the future., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: Accurate evaluation of tumor programmed death ligand 1 (PD-L1) expression can assist in predicting whether a patient will respond to anti-PD-L1 therapy. In this study, we aimed to develop stable radioiodinated PD-L1 antibodies that can be used for PD-L1 targeted SPECT/PET imaging., Methods: Radioiodination was accomplished via a prosthetic group ([ 131 I]SIB or [ 124 I]SIB) to give radioiodinated anti-human PD-L1 and anti-mouse PD-L1 antibody (anti-PD-L1 and anti-PD-L1 M ). MicroSPECT/PET imaging and biodistribution of radioiodinated antibodies were studied in two immune-competent murine models (B16F10 and 4T1 syngeneic tumor models) and patient-derived xenograft (PDX) model of lung adenocarcinoma to evaluate the feasibility of identifying tumor PD-L1 expression., Results: Radioiodinated PD-L1 antibodies had high radiochemical purity (>99%) and favorable stability in vivo. There was high uptake of [ 131 I]SIB-anti-PD-L1 M in both 4T1 and B16F10 syngeneic tumors when injected with 5.5 MBq radiotracers containing 200 μg anti-mouse-PD-L1. The presence of excess unlabeled anti-PD-L1 antibody increased [ 131 I]SIB-anti-PD-L1 M uptake in tumors. The highly specific PD-L1-positive tumor uptake detected by SPECT imaging indicated that radioiodinated antibody could be used for PD-L1 expression imaging. In addition, PET imaging of the PDX model was performed with [ 124 I]SIB-anti-PD-L1, which showed high signal intensity in tumors and optimal contrast between tumor and muscle (tumor-to-muscle ratios at 6 h p.i. and 24 h p.i. were 2.5 and 5.3, respectively)., Conclusions: This study provides an efficient strategy for synthesizing stable radioiodinated PD-L1 antibodies with excellent pharmacokinetics to identify PD-L1 expression in tumors., (Copyright © 2020. Published by Elsevier Inc.)

TSPO is up-regulated in activated macrophages, and serves as an attractive target for macrophages molecular imaging and therapy. MRI may be an ideal technique in the clinical management of RA due to its excellent spatial resolution. In the present study, a novel TSPO-targeting MRI contrast agent was developed by conjugating a novel TSPO ligand CB86 with gadolinium chelate to visualise inflamed regions in RA mice model. A novel TSPO ligand CB86 was linked to DTPAA, followed by chelation with gadolinium to obtain MRI targeted contrast agent CB86-DTPA-Gd. CB86-DTPA-Gd was characterised by MRI relaxivity, cell cytotoxicity, cell specificity and in vitro stability analysis. The distribution and MRI intensity was evaluated in RA rat model. Synthesis of CB86-DTPA-Gd was completed successfully with MRI relaxivity of 11.05/mM/sec (9.4 T, 25 °C). CB86-DTPA-Gd exhibited a good stability in human serum, high RAW264.7 cells specificity and no cytotoxicity in RAW264.7 cells. The biodistribution and MRI studies showed that the accumulation and signal intensity of CB86-DTPA-Gd in the right RA ankles was higher and stronger than those of Gd‑DTPA. This study demonstrates that CB86-DTPA-Gd can identify phagocytic active macrophages in the synovial joints, and has potential as a promising targeting MRI contrast agent for imaging of peripheral inflammation.

Stressed organelles are often challenging to image with canonical organelle probes owing to their propensity to dissipate from stressed organelles. We herein report the imaging of stressed lysosomes with color-switchable glyco-probes that contain an entity of mannose-6-carboxylate or sialic acid for targeting to and long-term retention in stressed lysosomes, and a diad of fluorescein/rhodamine-X-lactam exhibiting dramatic red-to-green fluorescence shift upon pH elevation. Relative to acidotropic dyes prone to dissipate from pH-elevated lysosomes, both glyco-probes are stably trapped in lysosomes without resorting to lysosomal acidity. Importantly, these probes are red emissive in acidic lysosomes (pH 4.5-5.8), but switched to green fluorescence in lysosomes of pH 6.0-7.4, allowing dual color discrimination of lysosomal pH alterations in cell starvation. These results support the use of sugar-armed sensors to investigate stressed lysosomes in biology and disease.

Diabetes mellitus (DM) and neurosyphilis (NS) may both damage the blood-brain barrier (BBB). It seems that non-neurosyphilis (non-NS) patients with high HbA 1c levels are likely to develop into NS. However, the correlation of HbA 1c level with BBB disruption in syphilis (non-NS) patients is unclear. In this study, we used dynamic contrast-enhanced (DCE) MRI to quantify regional BBB permeability in syphilis (non-NS) patients and detected several molecular biomarkers of cerebrospinal fluid (CSF). We found that BBB permeability values in the hippocampus, white matter, and cortex inferior temporal gyrus were correlated with albumin quotient (Qalb), CSF concentrations of interleukin IL-6 and IL-10. Moreover, BBB breakdown in white matter was correlated with CSF concentrations of sICAM-1 and sVCAM-1. In conclusion, our data suggest that BBB integrity may be liable to be disrupted in syphilis (non-NS) patients, patients with high HbA 1c levels, as well as syphilis (non-NS) patients with high HbA 1c levels, and it is particularly important to control blood glucose in these patients.