Activated macrophages are key effector cells and specific markers in patients with rheumatoid arthritis (RA). Cysteine cathepsin B (CTS-B) is highly expressed in macrophages and positively associated with RA activity and severity. This study aims to evaluate an activity-based multi-modality diagnostic agent, 68Ga-BMX2, which targets CTS-B to visualize the arthritis activity and evaluate the treatment efficacy. A CTS-B activity-based probe, BMX2, was labeled efficiently with 68Ga to produce 68Ga-BMX2 for fluorescent and positron emission tomography (PET) multi-modality imaging. The affinity and specificity of BMX2 binding with the CTS-B enzyme in macrophages were determined by radioactive experiment using RAW 264.7 cell lines, with CA074 and BMX5 as the inhibitors to test the specificity of the binding. Then, PET and fluorescence imaging were acquired on collagen-induced arthritis (CIA) mice. Additionally, the treatment monitoring capability of 68Ga-BMX2 PET/CT imaging was tested with methotrexate (MTX). RAW 264.7 macrophage cells showed significant uptake of 68Ga-BMX2. The binding of BMX2 with CTS-B in RAW 264.7 macrophage cells is time-dependent and could be blocked by CA074 and BMX5. In vivo optical and PET imaging showed high signals in the right hind arthritis in CIA mice from 68Ga-BMX2 and BMX2 accumulated for at least 120 h. Additionally, 68Ga-BMX2 signals were significantly reduced in the MTX-treated CIA mice compared to the control group. The 68Ga-BMX2, a radioactive and fluorescent dual-modality diagnostic agent targeting CTS-B, demonstrated a practical approach for CIA PET and fluorescence imaging. The 68Ga-BMX2 multimodality imaging could significantly monitor the treatment response in the CIA mice.

Most reported research has primarily investigated wild-type transthyretin cardiac amyloidosis (ATTRwt-CA). However, the application of bone scintigraphy for hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has not been systematically investigated. Therefore, in this study, we aimed to evaluate the diagnostic value of 99mTc-PYP scintigraphy in ATTRv-CA. Fifty-four patients were enrolled in a highly suspected cardiac amyloidosis cohort. Transthyretin (TTR) gene characteristics were summarized in the ATTRv-CA group. In 99mTc-PYP scintigraphy, the diagnostic efficiency of the visual score (VGS) and heart-to-contralateral chest (H/CL) ratio were evaluated. Furthermore, the interobserver consistency among the diagnosticians was investigated. Twenty-eight patients were diagnosed with ATTRv-CA with eight genotypes. The Ala97Ser genotype accounts for 46

Observational studies suggest a link between osteoarthritis (OA) and frailty, but the shared genetic architecture and causal relationships remain unclear. We analyzed X-ray and 18F-FDG PET/CT images in frail and non-frail individuals and conducted genetic correlation analyses using Linkage Disequilibrium Score Regression (LDSC) based on recent Genome-Wide Association Studies (GWAS) for OA and frailty. We identified pleiotropic single-nucleotide polymorphisms (SNPs) through Cross-Phenotype Association (CPASSOC) and Colocalization (COLOC) analyses and investigated genetic overlaps using Multi-marker Analysis of GenoMic Annotation (MAGMA). Transcriptome-wide association studies (TWAS) were conducted to analyze pleiotropic gene expression, and Mendelian Randomization (MR) was used to assess causal relationships between OA and frailty. Frail individuals showed more severe OA on X-ray (67% vs. 31%, P ≤ 0.01) and higher SUVmax on 18F-FDG PET/CT (4.1 vs. 3.6, P < 0.05) compared to non-frail individuals. Genetic correlation between frailty and OA was significant (rg = 0.532, P = 4.230E-88). Cross-trait analyses identified 42 genomic loci and 138 genes shared between the conditions. COLOC analysis revealed 2 pleiotropic loci, while TWAS identified 27 significant shared genetic expressions in whole blood and musculoskeletal tissue. Bidirectional MR indicated that OA increases the risk of frailty (IVW: beta: 0.13, P = 1.52E-08) and vice versa (IVW: beta: 0.73, P = 1.66E-04). Frail individuals exhibit more severe imaging features of OA. The shared genetic basis between OA and frailty suggests an intrinsic link, providing new insights into the relationship between these conditions.

Real-time detection of cellular senescence remains a clinical challenge. Here, we aimed to develop a positron emission tomography (PET) imaging probe targeting senescence-associated β-galactosidase (SA-β-Gal), the most widely used biomarker of cellular senescence, and investigate its performance for real-time in vivo quantitative detection of cellular senescence. A stable PET imaging agent [68Ga]Ga-BGal was obtained with a high labeling yield (90.0 ± 4.3%) and a radiochemical purity (>95%). [68Ga]Ga-BGal displayed high sensitivity and specificity for β-Gal both in vitro and in vivo. The reaction and uptake of the probe correlated with the β-Gal concentration and reaction time. In PET imaging, high β-Gal-expressing CT26.CL25 tumors and doxorubicin-treated HeLa tumors showed high signals from [68Ga]Ga-BGal, while a low signal was observed in CT26.WT and untreated HeLa tumors. In summary, we showcased successful PET imaging of senescence in preclinical models using probe [68Ga]Ga-BGal. This finding holds the potential for translating senescence imaging into clinical applications.

Objective:To investigate the effect of 18F-FDG combined with 18F-prostate specific membrane antigen (PSMA)-1007 PET/CT on TNM staging and clinical treatment decision of patients with prostate cancer. Methods:Clinical data and PET/CT images of 31 patients (age (69.9±9.2) years) with prostate cancer who underwent PET/CT imaging with 18F-FDG and 18F-PSMA-1007 (dual-tracer imaging) in the Second Xiangya Hospital of Central South University from June 2020 to March 2022 were retrospectively analyzed. Paired χ2 test was used to compare the diagnostic efficacy of 18F-FDG, 18F-PSMA-1007 and combined imaging for diagnosing primary prostate cancer, regional lymph node metastases and distant metastases, and to analyze the influence of combined imaging on clinical treatment decision. Results:There were 282 metastatic sites in 31 patients, including 46 regional lymph node metastases in 13 patients and 236 distant metastases in 15 patients. The detection rates of 18F-PSMA-1007 PET/CT and combined imaging for primary lesions were higher than the detection rate of 18F-FDG PET/CT (100%(31/31), 100%(31/31) vs 64.5%(20/31); χ2=13.37, P<0.001). Based on analysis of patients, the detection rates of 18F-PSMA-1007 PET/CT and combined imaging for regional lymph node metastases were higher than the detection rate of 18F-FDG PET/CT (12/13, 12/13 vs 6/13; χ2=4.51, P=0.034), and the 3 detection rates for distant metastases were also significantly different (15/15, 15/15 vs 10/15; χ2=6.00, P=0.042). Based on analysis of lesions, the detection rates of 18F-PSMA-1007 PET/CT and combined imaging for regional lymph node metastases were higher than the detection rate of 18F-FDG PET/CT (95.7%(44/46), 97.8%(45/46) and 45.7%(21/46); χ2 values: 25.37-49.56, all P<0.001). The detection rate of combined imaging for distant metastases was higher than that of 18F-FDG or 18F-PSMA-1007 PET/CT alone (96.2%(227/236) vs 68.6%(162/236), 58.9%(139/236)); and the detection rate of 18F-FDG PET/CT was higher than that of 18F-PSMA-1007 PET/CT ( χ2 values: 4.85-94.22, all P<0.05). Clinical treatment decisions in 10 patients (32.3%, 10/31) were changed based on the results of combined imaging. Conclusion:For prostate cancer with suspected distant metastases, 18F-FDG and 18F-PSMA-1007 dual-tracer PET/CT imaging can improve staging and guide clinical treatment decisions.

目的 探讨18F-氟脱氧葡萄糖(FDG)PET/CT在常见原发性胃淋巴瘤(PGL)[弥漫性大B细胞淋巴瘤(DLBCL)和黏膜相关淋巴样组织(MALT)淋巴瘤]组织病理学分型鉴别诊断和预后评估中的价值.方法 回顾性分析2015年3月至2022年3月于中南大学湘雅二医院行18F-FDGPET/CT检查的83例PGL患者的临床资料和影像资料,其中男性39例、女性44例,年龄范围为13～78岁,中位年龄为56(48,66)岁.根据组织病理学类型将患者分为DLBCL(46例)和MALT淋巴瘤(37例),比较2种类型PGL患者的临床特征[性别、年龄、Lugano分期、B症状、乳酸脱氢酶(LDH)水平、国际预后指数(IPI)、细胞增殖核抗原Ki-67(简称Ki-67)水平]、影像特征(胃壁厚度、胃壁增厚类型、病变部位、胃壁形态、胃外浸润)、代谢参数[最大标准化摄取值(SUVmax)、病灶糖酵解总量(TLG)、肿瘤代谢体积(MTV)]间的差异.计数资料用频数和百分比表示,组间比较采用卡方检验或Fisher确切概率法;符合正态分布的计量资料以(x)±s表示,组间比较采用两独立样本t检验;不符合正态分布的计量资料以M(Q1,Q3)表示,组间比较采用Mann-Whitney U检验.采用受试者工作特征(ROC)曲线分析代谢参数和胃壁厚度对鉴别DLBCL与MALT淋巴瘤的价值,对各代谢参数判断疾病进展的最佳临界值进行分类;采用Kaplan-Meier法进行生存分析,组间差异评估采用Log-rank法,对可能影响无进展生存(PFS)期的因素进行单因素和多因素Cox回归分析.结果 DLBCL较MALT淋巴瘤更易发生胃周浸润、胃腔肿块、胃窦受累、多部位受累和胃壁弥漫性增厚,且差异均有统计学意义(58.7％对 21.6％、21.7％对 2.7％、71.7％对 35.1％、54.3％对 32.4％、43.5％对 27.0％,x2=3.99～11.56,均P＜0.05);DLBCL患者的胃壁厚度、TLG、SUVmax显著高于MALT淋巴瘤患者[20.5(13.0,32.3)mm 对 12.0(10.0,16.5)mm、603.2(138.8,1 971.0)g 对 69.9(22.3,208.3)g、23.4±11.5 对 6.6±3.9],差异均有统计学意义(Z=-3.72、-4.24,t=-9.30,均P＜0.05).ROC 曲线分析结果显示,SUVmax、TLG、胃壁厚度对鉴别MALT淋巴瘤与DLBCL诊断效能的差异均有统计学意义(AUC=0.915、0.772、0.738,均P＜0.05),当SUVmax=11.95为临界值时,灵敏度为80.4％,特异度为91.9％.Kaplan-Meier生存分析结果显示,DLBCL患者的胃壁厚度、SUVmax、TLG、MTV与PFS率相关,差异均有统计学意义(x2=6.98～12.71,均P＜0.01);MALT淋巴瘤患者的年龄、Lugano分期、IPI、Ki-67、胃壁弥漫性增厚与PFS率相关,差异均有统计学意义(x2=4.31～15.11,均P＜0.05).单因素Cox回归分析结果显示,胃壁厚度、SUVmax、TLG、MTV为DLBCL患者PFS期的危险因素(HR=5.749～8.768,均P＜0.05);胃壁增厚类型为MALT淋巴瘤患者PFS期的危险因素(HR=8.683,P=0.022).多因素回归分析结果显示,SUVmax为DLBCL患者PFS期的独立危险因素(HR=9.317,P=0.047).结论 DLBCL和MALT淋巴瘤的18F-FDG PET/CT显像有一定特征性,18F-FDG PET/CT代谢参数既可以鉴别DLBCL与MALT淋巴瘤,同时也可以预测DLBCL患者的预后.