Sunitinib is an anti-angiogenic drug that can induce drug resistance characterized by hypoxia. We aimed to synthesize two novel radiolabeled LyP-1 peptides, 99mTc-HYNIC-LyP-1 and 131I-LyP-1, to detect sunitinib-induced changes in the tumor microenvironment and improve the therapeutic effects in triple-negative breast cancer (TNBC) mice models. We synthesized 99mTc-HYNIC-LyP-1 using hydrazinonicotinamide (HYNIC) as the chelating agent and labeled the LyP-1 peptide with 131I using the chloramine-T method to synthesize 131I-LyP-1. Radiochemical purity and stability of the peptides were assessed in vitro using thin-layer chromatography. Tumor accumulation and biodistribution of 99mTc-HYNIC-LyP-1 were measured in 4T1 xenografts with or without sunitinib treatment. Immunohistochemical analysis was performed to detect sunitinib-induced changes. The therapeutic potential of 131I-LyP-1 alone and in combination with sunitinib was evaluated in a TNBC mouse model. 99mTc-HYNIC-LyP-1 and 131I-LyP-1 could be readily prepared with satisfactory labeling efficiency (95.4

Correction for 'Phosphorus core-shell tecto dendrimers for enhanced tumor imaging: the rigidity of the backbone matters' by Mengsi Zhan et al., Biomater. Sci., 2023, 11, 7387-7396.

Abstract Background Programmed cell death 1/programmed death ligand-1 (PD-L1)-based immune checkpoint blockade is an effective treatment approach for non-small-cell lung cancer (NSCLC). However, immunohistochemistry does not accurately or dynamically reflect PD-L1 expression owing to its spatiotemporal heterogeneity. Herein, we assessed the feasibility of using a 68Ga-labeled anti-PD-L1 nanobody, 68Ga-NODAGA-NM-01, for PET imaging of PD-L1. Methods Micro-PET/CT and biodistribution studies were performed on PD-L1-positive and -negative tumor-bearing mice. Additionally, a preliminary clinical study was performed on two patients with NSCLC. NM-01 was radiolabeled with 68Ga without further purification under mild conditions. Results 68Ga-NODAGA-NM-01 exhibited radiochemical purity (> 98%), high stability in vitro, and rapid blood clearance in vivo. Specific accumulation of 68Ga-NODAGA-NM-01 was observed in PD-L1-positive tumor-bearing mice, with a good tumor-to-background ratio 0.5h post-injection. Furthermore, 68Ga-NODAGA-NM-01 PET/CT imaging was found to be safe with no adverse events and distinct uptake in primary and metastatic lesions of the PD-L1-positive patient, with a higher maximal standardized uptake value than that in lesions of the PD-L1-negative patient 1h post-injection. Conclusions 68Ga-NODAGA-NM-01 can be prepared using a simple method under mild conditions and reflect PD-L1 expression in primary and metastatic lesions. However, our findings need to be confirmed in a large cohort. Trial registration NCT02978196. Registered February 15, 2018.

As an emerging therapeutic tool, small interfering RNA (siRNA) had the capability to down-regulate nearly all human mRNAs via sequence-specific gene silencing. Numerous studies have demonstrated the substantial potential of siRNA in the treatment of broad classes of diseases. With the discovery and development of various delivery systems and chemical modifications, six siRNA-based drugs have been approved by 2024. The utilization of siRNA-based therapeutics has significantly propelled efforts to combat a wide array of previously incurable diseases and advanced at a rapid pace, particularly with the help of potent targeted delivery systems. Despite encountering several extracellular and intracellular challenges, the efficiency of siRNA delivery has been gradually enhanced. Currently, targeted strategies aimed at improving potency and reducing toxicity played a crucial role in the druggability of siRNA. This review focused on recent advancements on ionizable lipid nanoparticles (LNPs) and cationic polymer (CP) vectors applied for targeted siRNA delivery. Based on various types of targeted modifications, we primarily described delivery systems modified with receptor ligands, peptides, antibodies, aptamers and amino acids. Finally, we discussed the challenges and opportunities associated with siRNA delivery systems based on ionizable LNPs and CPs vectors.

A deep progressive learning method for PET image reconstruction named deep progressive reconstruction (DPR) method was developed and presented in previous works. It has been shown in previous study that the DPR with one-third duration can maintain the image quality as OSEM with standard dose (3.7 MBq/kg). Subsequent studies have shown we can reduce the administered activity of 18F-FDG by up to 2/3 in a real-world deployment with DPR. The aim of this study is to assess the impact of the use of DPR on Deauville score (DS) and clinical interpretation of PET/CT in patients with lymphoma. A total of 87 lymphoma patients (age, 45.1 ± 14.9 years) who underwent 18F-FDG PET imaging for during or post-treatment follow-up from November 2020 to February 2024 were prospectively enrolled. The patients were randomly assigned to two groups, including the 1/3 standard dose group and the standard dose group. Forty-four patients were injected with 1/3 standard dose (1.23 MBq/kg) and scanned for 6 min per bed and were reconstructed: ordered-subsets expectation maximization (OSEM) with 6 min per bed (OSEM_6 min_1/3), OSEM_2 min_1/3 and DPR_2 min_1/3. Forty-three patients were scanned according to the standard protocol (3.7 MBq/kg) and were reconstructed: OSEM with 2 min per bed (OSEM_2 min_full), OSEM_40 s_full and DPR_40 s_full. Additionally, the conventional 5-point scale measurement analysis was performed and DS for lymphoma were determined in different groups. Wilcoxon signed-rank test was used to compare the mean values of liver SUVmax and mediastinal blood pool (MBP) SUVmax in each group. Likert scale and DS were evaluated using Wilcoxon signed rank test. The patients with OSEM_6 min_1/3 and DPR_2 min_1/3 showed good image quality with 5(5,5) and 5(4,5) of Likert scoring, as well as the patients with OSEM_2 min_full and DPR_40 s_full. No significant difference was found between the OSEM_6 min_1/3 and DPR_2 min_1/3 groups in terms of liver SUVmax and MBP SUVmax (P = 0.452 and 0.430), as well as the patients with OSEM_2 min_full and DPR_40 s_full (P = 0.105 and 0.638). No significant difference was found between the OSEM_6 min_1/3 and DPR_2 min_1/3 groups in terms of lesion SUVmax (P = 0.080). There was a significant differences in lesion SUVmax between OSEM-2 min_full with DPR-40 s_full (P = 0.027). The DS results were consistent (100

Background 99m Tc radiolabeled nanobody NM-02 ( 99m Tc-NM-02) is a novel single photon emission computed tomography (SPECT) probe with a high affinity and specificity for human epidermal growth factor receptor 2 (HER2). In this study, a clinical imaging trial was conducted to investigate the relationship between 99m Tc-NM-02 uptake and HER2 expression in patients with breast cancer. Methods Thirty patients with pathologically confirmed breast cancer were recruited and imaged with both 99m Tc-NM-02 SPECT/computed tomography (CT) and 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/CT. According to the treatment conditions before recruitment, patients were divided into two groups, the newly diagnosed group ( n = 24) and the treated group ( n = 6). The maximal standard uptake value (SUV max ) of 18 F-FDG and SUV max and mean SUV (SUV mean ) of 99m Tc-NM-02 in the lesions were determined to analyze the relationship with HER2 expression. Results No meaningful relationship was observed between 18 F-FDG uptake and HER2 expression in 30 patients with breast cancer. 99m Tc-NM-02 uptake was positively correlated with HER2 expression in the newly diagnosed group, but no correlation was observed in the treated group. 99m Tc-NM-02 uptake in HER2-positive lesions was lower in those with effective HER2-targeted therapy compared with the newly diagnosed group. 99m Tc-NM-02 SPECT/CT detected brain and bone metastases of breast cancer with a different imaging pattern from 18 F-FDG PET/CT. 99m Tc-NM-02 showed no non-specific uptake in inflamed tissues and revealed intra- and intertumoral HER2 heterogeneity by SPECT/CT imaging in 9 of the 30 patients with breast cancer. Conclusions 99m Tc-NM-02 SPECT/CT has the potential for visualizing whole-body HER2 overexpression in untreated patients, making it a promising method for HER2 assessment in patients with breast cancer. Trial registration NCT04674722, Date of registration: December 19, 2020.

Therapeutic resistance is an essential challenge for nanotherapeutics. Herein, a narrow bandgap RuI3 nanoplatform has been constructed firstly to synergize radiotherapy (RT), photothermal therapy (PTT), and thermoelectric dynamic therapy (TEDT) for tumor eradication. Specifically, the photothermal performance of RuI3 can ablate tumor cells while inducing TEDT. Noteworthy, the thermoelectric effect is found firstly in RuI3, which can spontaneously generate an electric field under the temperature gradient, prompting carrier separation and triggering massive ROS generation, thus aggravating oxidative stress level and effectively inhibiting HSP-90 expression. Moreover, RuI3 greatly enhances X-ray deposition owing to its high X-ray attenuation capacity, resulting in a pronounced computed tomography imaging contrast and DNA damage. In addition, RuI3 possesses both catalase-like and glutathione peroxidase-like properties, which alleviate tumor hypoxia and reduce antioxidant resistance, further exacerbating 1O2 production during RT and TEDT. This integrated therapy platform combining PTT, TEDT, and RT significantly inhibits tumor growth.Statement of SignificanceRuI3 nanoparticles were synthesized for the first time. RuI3 exhibited the highest photothermal properties among iodides, and the photothermal conversion efficiency was 53.38%. RuI3 was found to have a thermoelectric effect, and the power factor could be comparable to that of most conventional thermoelectric materials. RuI3 possessed both catalase-like and glutathione peroxidase-like properties, which contributed to enhancing the effect of radiotherapy.

RATIONALE AND OBJECTIVES:To construct a multiparameter radiomics nomogram based on ultrasound (US) to predict the aggressiveness of thyroid papillary carcinoma (PTC). MATERIALS AND METHODS:In total, 471 consecutive patients from three institutions were included in this study. Among them, patients from institution 1 were used for training (n = 294) and internal validation (n = 92), while 85 patients from institution 2 and institution 3 were used for external validation. Radiomics features were extracted from the conventional US. The least absolute shrinkage was employed to select the most relevant features for the aggressiveness of PTC, along with the maximum relevance minimum redundancy algorithm and selection operator. These features were then used to construct the radiomics signature (RS). Subsequently, relevant multiparameter ultrasound (MPUS) features from shear-wave elastic (SWE) and strain elastography (SE) will be extracted using multivariable logistic regression. The final radionics nomogram was conducted using the RS, clinical information, and conventional US and MPUS features. The receiver operating characteristic (ROC), calibration, and decision curves were used to evaluate the performance of the nomogram. RESULTS:Multivariable logistic regression analysis indicated that age, nodule size, capsule abutment, SWV tumor, and RS were independent predictors of the aggressiveness of PTC. The radiomics nomogram, utilizing these characteristics, displayed impressive performance with an AUC of 0.920 [95% CI, 0.889-0.950], 0.901 [95% CI, 0.839-0.963], and 0.896 [95% CI, 0.823-0.969] in the training, internal, and external validation cohort. It outperformed the clinical US, MPUS, and RS models (p < 0.05). The decision curve analysis indicated that the nomogram offered valuable clinical utility. CONCLUSION:The nomogram incorporated MPUS and radiomics have good diagnostic performance in predicting the aggressiveness of PTC which may help in the selection of the surgical modality.

ABSTRACT:A 27-year-old woman underwent 68 Ga-pentixafor PET/CT for primary aldosteronism localization and characterization. No functional adrenal nodules were detected by 68 Ga-pentixafor PET/CT, whereas a hypodense nodule with focal pentixafor uptake was incidentally discovered in the head of pancreas. Retrospective analysis of contrast-enhanced CT scan revealed a subtly enhancing nodule devoid of calcification in the pancreatic head. Pancreatic cancer cannot be excluded. 18 F-FDG PET/CT was suggested, and the scan showed an FDG-avid lesion in the same region. Needle biopsy was performed, and the pathological result is solid pseudopapillary tumor, a rare pancreatic tumor of low malignant potential.

Tumor immunotherapy represents a highly promising modality for the treatment of triple-negative breast cancer (TNBC). Nevertheless, its therapeutic efficacy has been profoundly impacted by challenges such as low drug uptake, hypoxia, and immunosuppression. To address these problems, the study develops a strategy combining sonodynamic therapy (SDT) and immunotherapy using biomimetic nanoparticles coated with hybrid membranes. The nanoparticles are loaded with semiconducting polymers (PFODBT), Atovaquone (ATO), and TMP195 to enhance biocompatibility, targeting ability, and drug uptake and retention at the tumor site. In in vitro experiments, the biomimetic nanoparticles alleviate hypoxia, induce immunogenic cell death (ICD), and prompt reprogramming of tumor-associated macrophages (TAMs) from M2 type to M1 type. In in vivo experiments, the synergistic effects of enhanced SDT-mediated ICD and TAMs repolarization significantly inhibit the proliferation of primary and distant tumor in the 4T1 subcutaneous tumor model, and effectively attenuated metastasis of lung and liver. Moreover, the in vivo immune responses are further activated by improving the maturation of dendritic cells, filtration of CD8+ T cells, and depletion of regulatory T cells. This study offers a novel strategy for TNBC therapy by converting the tumor microenvironment from the "cold" into "hot" tumor through multiple synergistic therapies.

177Lu- prostate specific membrane antigen (PSMA) radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China. Based on domestic clinical practice and experimental data and referred to international experience and viewpoints, the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Wilson's disease (WD) is a genetic disorder that primarily leads to the pathological accumulation of copper (Cu) in the liver, causing an abnormal increase in reactive oxygen species (ROS). The prevailing clinical therapy for WD involves lifelong use of Cu chelation drugs to facilitate Cu excretion in patients. However, most available drugs exert severely side-effects due to their non-specific excretion of Cu, unsuitable for long-term use. In this study, we construct a prochelator that enables precise and controlled delivery of Cu chelator drugs to the liver in WD model, circumventing toxic side effects on other organs and normal tissues. This innovative prochelator rapidly releases the chelator and the fluorescent molecule methylene blue (MB) upon activation by ROS highly expressed in the liver of WD. The released chelator coordinates with Cu, efficiently aiding in Cu removal from the body and effectively inhibiting the pathological progression of WD.

This study aimed to identify the prognostic value of interim 18F-FDG PET/CT (I-PET) for germinal center B-cell-like (GCB) and non-GCB diffuse large B-cell lymphoma (DLBCL), respectively. Baseline 18F-FDG PET/CT (B-PET) and I-PET scans were performed in 112 patients with DLBCL. The prognostic value of I-PET using the Deauville five-point scale (D-5PS) criteria or percentage decrease in SUVmax (∆SUVmax) for GCB and non-GCB DLBCL were evaluated. A significant difference in progression-free survival (PFS) was found between GCB and non-GCB DLBCL patients (P < 0.05). Based on D-5PS criteria, I-PET was divided into positive (score > 3) and negative (score ≤ 3) subgroups. Results indicated that I-PET using D-5PS criteria was an independent predictor for PFS of GCB DLBCL (P < 0.05), but not for overall survival (OS) (P > 0.05). For non-GCB DLBCL, PFS and OS were significantly higher in I-PET negative group than I-PET positive group (P < 0.05). Receiver operating characteristic (ROC) curve analysis proved that I-PET using ΔSUVmax can also effectively predict PFS and OS of non-GCB DLBCL (P < 0.05), but not for GCB DLBCL (P > 0.05). Based on the optimal threshold found by ROC curve analysis, patients were dichotomized into ∆SUVmax high and low groups. Log-rank test and Cox regression demonstrated that the layered ∆SUVmax was predictive of PFS and OS in non-GCB DLBCL (P < 0.05). I-PET may have different prognostic values for GCB and non-GCB DLBCL. Thus, the pathology type of DLBCL may be considered while using I-PET as a prognostic tool in the future.

Plectin, a scaffolding protein overexpressed in tumor cells, plays a significant role in hepatocellular carcinoma (HCC) proliferation, invasion, and migration. However, the use of L-type peptides for targeting plectin is hindered by their limited stability and retention. We designed a D-type plectin-targeting peptide (DPTP) and developed a novel single-photon emission computed tomography (SPECT) probe for HCC imaging. The DPTP targeting ability was evaluated in vitro using flow cytometry and ex vivo fluorescence imaging. 99mTc radiolabeling was performed using tricine and ethylenediamine-N,N '-diacetic acid (EDDA) as coligands after modification with 6-hydrazino nicotinamide (HYNIC) at the N termini of DPTP. The radiochemical purity (RCP), in vitro stability, and binding affinity of the prepared 99mTc-HYNIC-DPTP were analyzed. Tumor uptake, metabolic stability, biodistribution, and pharmacokinetics of 99mTc-HYNIC-DPTP were investigated and compared with those of 99mTc-labeled L-type PTP (99mTc-HYNIC-PTP) in HCC tumor-bearing mice. DPTP could be efficiently radiolabeled with 99mTc using the HYNIC/tricine/EDDA system with a high RCP and good in vitro stability. Compared with the L-type PTP, DPTP exhibited improved targeting ability, and 99mTc-HYNIC-DPTP displayed higher tumor uptake, better metabolic stability, longer blood circulation time, and lower kidney retention, resulting in superior imaging performance and biodistribution in vivo. 99mTc-HYNIC-DPTP has great potential as a novel SPECT probe for diagnosing HCC.

Objective:To evaluate the feasibility of PET automatic drug infusion system combined with power peripherally inserted central catheter (PICC) for 18F-FDG injection and PET/CT imaging. Methods:Fifty patients with malignant neoplasms who underwent 18F-FDG PET/CT imaging in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine between December 2021 to July 2022 were prospectively enrolled. They were equally divided into power PICC group and peripheral venipuncture group. PET automatic drug infusion system was respectively connected with the pre-established channels of power PICC and peripheral venipuncture for 18F-FDG injection. Each patient underwent a routine PET/CT imaging at 1 h post-injection. The blood glucose, body weight, prescription dose and injection dose were recorded, and SUV max in the liver and cavoatrial junction were measured in both groups. The independent-sample t test was performed to compare the differences between 2 groups. The power PICC tip positions after 18F-FDG injection in power PICC group were observed. Results:The liver SUV max in the power PICC group and peripheral group were 2.54±0.50 and 2.57±0.31 ( t=0.37, P=0.716), and the SUV max of cavoatrial junction in the 2 groups were 1.68±0.25 and 1.63±0.22 ( t=-0.78, P=0.441), respectively. No significant differences were found in blood glucose, body weight, prescription dose and injection dose between the 2 groups ( t values: 0.00-0.13, all P>0.05). The ratios of injection dose to prescription dose in the 2 groups were 0.998 3±0.007 3 and 0.997 6±0.016 5, respectively, indicating high injection accuracy of the injection methods. No obvious drug residue was displayed at the end of catheter, resulting in good imaging quality. All the tip positions after injection were between T5 and T8, in line with the standardization management of power PICC. Conclusion:PET automatic drug infusion system combined with power PICC can be safely used for 18F-FDG injection and PET/CT imaging with less injection puncture.

The prognostic value of interim 18F-FDG PET/CT (I-PET) for follicular lymphoma (FL) is controversial, and may be related to the lack of strict standards in terms of age, chemotherapy regimen, and evaluation criteria in previous studies. This study aimed to investigate the prognostic value of I-PET in adult FL patients treated with R-CHOP. I-PET was performed in 30 adult FL patients after treatment with 3–5 cycles of R-CHOP. PET/CT images were assessed using the Deauville 5-point scale (D-5PS) criteria. Baseline PET/CT (B-PET) was performed in 24 of the patients with FL before treatment. The PET/CT image parameters, such as the SUVmax, TLG, and tMTV, were recorded. The prognostic values of sex, age, grade, Ann Arbor stage, LDH level, and I-PET were evaluated. Kaplan-Meier analysis and Cox regression showed that sex, age, grade, Ann Arbor stage, LDH, and I-PET using the D-5PS criteria could not predict the PFS of adult patients with FL treated with R-CHOP (P>0.05). ROC curve analysis evaluated the predictive values of SUVmax, TLG, and tMTV in B-PET and I-PET and showed that none of them was predictive of PFS in adult FL patients (P>0.05). However, the variation in SUVmax (∆SUVmax) was predictive of PFS in adult FL patients (AUC=0.83, P=0.040), and the cutoff threshold was 4.85. I-PET using the D-5PS criteria cannot predict the PFS of adult FL patients treated with R-CHOP. However, the ∆SUVmax between B-PET and I-PET is applicable for the prognosis of adult patients with FL.

目的 探讨PSMA靶向分子探针 68Ga-THP-PSMA的制备,并初步评价该探针在诊断国内前列腺癌患者术后复发和转移中的价值.资料与方法 采用THP-PSMA药盒室温一步法制备 68Ga-THP-PSMA标记物,经0.22 μm无菌微孔滤膜过滤除菌,测定标记物细菌内毒素、放化纯和体外稳定性;前瞻性纳入2019年11月—2020年 3月上海交通大学医学院附属第一人民医院前列腺癌患者10例,静脉注射 68Ga-THP-PSMA后行1 h常规全身PET/CT显像和2 h延迟PET/CT显像,比较常规显像和延迟显像病灶的最大标准化摄取值(SUVmax),分析 68Ga-THP-PSMA阳性率与前列腺特异性抗原水平的关系.结果 THP-PSMA与 68GaCl3室温混合5 min后,标记率>95%[(98.74±1.06)%,n=10],在室温PBS体系和 37℃血清中具有良好的体外稳定性.10例前列腺癌患者的PET/CT显像显示,68Ga-THP-PSMA在肾脏和膀胱分布最高,其次为肝脏、脾脏和小肠,提示显像剂主要通过泌尿系统排泄;唾液腺、泪腺有较多生理性摄取;4 例患者共21个病灶具有明显摄取,判定为局部复发或转移灶;病灶的SUVmax值在1 h和2 h显像差异无统计学意义(12.74±1.68比13.44±1.67,t=0.59,P=0.28);经 68Ga-THP-PSMA判定为PET/CT显像阳性患者的前列腺特异性抗原水平显著高于 PET/CT 阴性患者(t=0.81,P=0.04).结论 68Ga-THP-PSMA 制备简单、快速、标记率稳定,可浓聚于前列腺癌病灶,信噪比高,对诊断前列腺癌术后复发或转移具有临床潜力.