Talaromyces marneffei: A challenging diagnosis in a kidney transplant patient.

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.

A firm-push-to-open and light-push-to-lock strategy for a general chemical platform to develop activatable dual-modality NIR-II probes.

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 (H2O2) and hydrogen sulfide (H2S). We envision a widespread adoption of the chemical platform for designing activatable NIR-II probes across diverse applications.

A dynamic online nomogram predicting prostate cancer short-term prognosis based on 18F-PSMA-1007 PET/CT of periprostatic adipose tissue: a multicenter study.

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 18F-PSMA-1007 PET/CT of PPAT. METHODS: Data from 268 prostate cancer (PCa) patients who underwent 18F-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.

Tuning the photophysical properties of cyanine by barbiturate functionalization and nanoformulation for efficient optoacoustics- guided phototherapy.

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 (PEG114-b-PCL60) 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.

Development and validation of [18 F]-PSMA-1007 PET-based radiomics model to predict biochemical recurrence-free survival following radical prostatectomy.

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.

Progressive Optimization of Lanthanide Nanoparticle Scintillators for Enhanced Triple-Activated Radioluminescence Imaging.

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, NaGdF4 : 15 %Eu@NaLuF4 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 ß-electrons into visible photon signals, thus establishing a robust nanotechnology-aided approach for tumor-directed radio-phototheranostics.

The additional value of 18F-FDG PET/CT imaging in guiding the treatment strategy of non-tuberculous mycobacterial patients.

OBJECTIVES: Non-tuberculous mycobacteria (NTM) infection is an increasing health problem due to delaying an effective treatment. However, there are few data on 18F-FDG PET/CT for evaluating the status of NTM patients. The aim of this study was to investigate the potential value of 18F-FDG PET/CT in guiding the treatment strategy of NTM patients. METHODS: We retrospectively analyzed the cases of 23 NTM patients who underwent 18F-FDG PET/CT. The clinical data, including immune status and severity of NTM pulmonary disease (NTM-PD), were reviewed. The metabolic parameters of 18F-FDG included maximum standardized uptake value (SUVmax), SUVmax of the most FDG-avid lesion (SUVTop), SUVTop/SUVmax of the liver (SURLiver), SUVTop/SUVmax of the blood (SURBlood), 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 18F-FDG uptake (median SUVTop: 8.2 ± 5.7). As for immune status, the median SUVTop 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, SURLiver and SURBlood 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, SUVmax of the lung lesion (SUVI-lung) and SUVmax of the marrow (SUVMarrow) 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 SUVTop, SURLiver, SURBlood, SUVI-lung, and SUVMarrow had a high sensitivity and specificity for the identification of immune status, lesion extent, and severity of disease in NTM patients. CONCLUSION: 18F-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.

New techniques to identify the tissue of origin for cancer of unknown primary in the era of precision medicine: progress and challenges.

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.

Unusual 131 I Uptake Caused by Paronychia in a Patient With Papillary Thyroid Cancer.

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.

A continuously efficient O2-supplying strategy for long-term modulation of hypoxic tumor microenvironment to enhance long-acting radionuclides internal therapy.

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 H2O2 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 H2O2 into O2 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.

18F-FAPI-04 Outperforms 18F-FDG PET/CT in Clinical Assessments of Patients with Pancreatic Adenocarcinoma.

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 18F-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in evaluation of PDAC and compared the findings with those obtained using 18F-FDG. Methods: Sixty-two PDAC patients underwent 18F-FAPI-04 PET/CT and 18F-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 SUVmax of the primary lesion and treatment response was explored in patients who received systemic therapy. Results: 18F-FAPI-04 PET/CT identified all patients with PDAC; 18F-FDG PET/CT missed 1 patient. Tracer uptake was higher in 18F-FAPI-04 PET/CT than in 18F-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 18F-FAPI-04 PET/CT than for 18F-FDG PET/CT (P = 0.002 and 0.008, respectively). Thus, 14 patients were upgraded, and only 1 patient was downgraded, by 18F-FAPI-04 PET/CT compared with 18F-FDG PET/CT. A high SUVmax of the primary tumor did not correlate with treatment response for either 18F-FAPI-04 or 18F-FDG. Conclusion: 18F-FAPI-04 PET/CT performed better than 18F-FDG PET/CT in identification of primary tumors, LN metastasis, and DM and in TNM staging of PDAC.

A case of TM infection with challenging differential diagnosis from lymphoma post-renal transplant.

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.

Fibroblast Activation Protein-Targeted PET/CT With Al18F-NODA-FAPI-04 for In Vivo Imaging of Tendon Healing in Rat Achilles Tendon Injury Models.

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 (Al18F-NODA-FAPI-04) administered on the first day of each week and 18F-fludeoxyglucose (18F-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, Al18F-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 18F-FDG experiencing a more rapid decrease than Al18F-NODA-FAPI-04. In the fourth week after surgery, the maximum standardized uptake values of Al18F-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. Al18F-NODA-FAPI-04 PET allows accurate localization and provides detailed morphological imaging, enabling continuous monitoring of the healing progress and assessment of injury severity.

Cerenkov radiation-mediated in situ activation of silicon nanocrystals for NIR optical imaging.

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.

Integrated analysis of comorbidity, pregnant outcomes, and amniotic fluid cytogenetics of fetuses with persistent left superior vena cava.

BACKGROUND: Persistent left superior vena cava (PLSVC) is the most common venous system variant. The clinical characteristics and amniotic fluid cytogenetics of fetuses with PLSVC remain to be further explored. AIM: To develop reliable prenatal diagnostic recommendations through integrated analysis of the clinical characteristics of fetuses with PLSVC. METHODS: Cases of PLSVC diagnosed using prenatal ultrasonography between September 2019 and November 2022 were retrospectively studied. The clinical characteristics of the pregnant women, ultrasonic imaging information, gestational age at diagnosis, pregnancy outcomes, and amniocentesis results were summarized and analyzed using categorical statistics and the chi-square test or Fisher's exact test. RESULTS: Of the 97 cases diagnosed by prenatal ultrasound, 49 (50.5%) had isolated PLSVC and 48 (49.5%) had other structural abnormalities. The differences in pregnancy outcomes and amniocentesis conditions between the two groups were statistically significant (P < 0.05). No significant differences were identified between the two groups in terms of advanced maternal age and gestational age (P > 0.05). According to the results of the classification statistics, the most common intracardiac abnormality was a ventricular septal defect and the most common extracardiac abnormality was a single umbilical artery. In the subgroup analysis, the concurrent combination of intra- and extracardiac structural abnormalities was a risk factor for adverse pregnancy outcomes (odds ratio > 1, P < 0.05). Additionally, all abnormal cytogenetic findings on amniocentesis were observed in the comorbidity group. One case was diagnosed with 21-trisomy and six cases was diagnosed with chromosome segment duplication. CONCLUSION: Examination for other structural abnormalities is strongly recommended when PLSVC is diagnosed. Poorer pregnancy outcomes and increased amniocentesis were observed in PLSVC cases with other structural abnormalities. Amniotic fluid cytogenetics of fetuses is recommended for PLSVC with other structural abnormalities.

Recurrence hyperparathyroidism caused by synchronous parathyroid carcinoma and parathyromatosis in a patient with long-term hemodialysis.

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.

False-Positive 131 I Uptake After Posttraumatic Scab in a Patient With Papillary Thyroid Carcinoma.

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.

Identification of Candidate Biomarkers of Alzheimer's Disease via Multiplex Cerebrospinal Fluid and Serum Proteomics.

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.

Assessment of pulmonary fibrosis induced by paraquat using Al18F-NODA-FAPI-04 PET/CT.

The lack of a highly sensitive method to evaluate paraquat (PQ)-induced pulmonary fibrosis and predict disease progression remains an unresolved clinic issue. Fibroblast activation protein (FAP) may play an important role in the pathogenesis of PQ-induced pulmonary fibrosis. We aimed to evaluate the role of FAP in the PQ-induced pulmonary fibrosis and the utility of fibroblast activation protein inhibitor (FAPI) for positron emission tomography (PET) imaging in PQ-induced pulmonary fibrosis. In our study, two cases of PQ poisoning were presented and FAPI PET/CT was performed as a novel imaging technique. The uptake of FAPI increased in both cases of PQ poisoning. Animal experiments were then performed to validate the findings in the patients. Physiological FAPI lung uptake was higher in mice of the PQ group than in the control group. The results of histological analysis and Western blot were consistent with the findings of PET/CT imaging. The pulmonary fibrosis animal model was developed by intragastric gavage of PQ. PET/CT imaging was performed after injection of FAPI. Lung tissues of mice were collected for fibrosis assessment after imaging. Immunohistochemistry for FAP, histology and Western blot for collagen were performed to further validate the imaging findings. In conclusion, FAPI was involved in the pathogenesis of fibrosis induced by PQ, and PET/CT with FAPI could detect lung fibrogenesis, making it a promising tool to assess early disease activity and predict disease progression.