Janus ACSP Nanoparticle for Synergistic Chemodynamic Therapy and Radiosensitization.

Protective autophagy and DNA damage repair lead to tumor radio-resistance. Some hypoxic tumors exhibit a low radiation energy absorption coefficient in radiation therapy. High doses of X-rays may lead to side effects in the surrounding normal tissues. In order to overcome the radio-resistance and improve the efficacy of radiotherapy based on the characteristics of the tumor microenvironment, the development of radiosensitizers has attracted much attention. In this study, a Janus ACSP nanoparticle (NP) was developed for chemodynamic therapy and radiosensitization. The reactive oxygen species generated by the Fenton-like reaction regulated the distribution of cell cycles from a radioresistant phase to a radio-sensitive phase. The high-Z element, Au, enhanced the production of hydroxyl radicals (•OH) under X-ray radiation, promoting DNA damage and cell apoptosis. The NP delayed DNA damage repair by interfering with certain proteins involved in the DNA repair signaling pathway. In vivo experiments demonstrated that the combination of the copper-ion-based Fenton-like reaction and low-dose X-ray radiation enhanced the effectiveness of radiotherapy, providing a novel approach for synergistic chemodynamic and radiosensitization therapy. This study provides valuable insights and strategies for the development and application of NPs in cancer treatment.

Imaging of Tumor Stroma Using 68Ga-FAPI PET/CT to Improve Diagnostic Accuracy of Primary Tumors in Head and Neck Cancer of Unknown Primary: A Comparative Imaging Trial.

The low detection rate of primary tumors by current diagnostic techniques remains a major concern for patients with head and neck cancer of unknown primary (HNCUP). Therefore, in this study, we aimed to investigate the potential role of 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET/CT compared with 18F-FDG PET/CT for the detection of primary tumors of HNCUP. Methods: In this prospective comparative imaging trial conducted at Fudan University Shanghai Cancer Center, 91 patients with negative or equivocal findings of a primary tumor by comprehensive clinical examination and conventional imaging were enrolled from June 2020 to September 2022. The presence of a primary tumor was recorded by 3 experienced nuclear medicine physicians. Primary lesions were validated by histopathologic analysis and a composite reference standard. Results: Of the 91 patients (18 women, 73 men; median age, 60 y; age range, 24-76 y), primary tumors were detected in 46 (51%) patients after a thorough diagnostic work-up. 68Ga-FAPI PET/CT detected more primary lesions than 18F-FDG PET/CT (46 vs. 17, P < 0.001) and showed better sensitivity, positive predictive value, and accuracy in locating primary tumors (51% vs. 25%, 98% vs. 43%, and 51% vs. 19%, respectively). Furthermore, 68Ga-FAPI PET/CT led to treatment changes in 22 of 91 (24%) patients compared with 18F-FDG PET/CT. The Kaplan-Meier curve illustrated that patients with unidentified primary tumors had a significantly worse prognosis than patients with identified primary tumors (hazard ratio, 5.77; 95% CI, 1.86-17.94; P = 0.0097). Conclusion: 68Ga-FAPI PET/CT outperforms 18F-FDG PET/CT in detecting primary lesions and could serve as a sensitive, reliable, and reproducible imaging modality for HNCUP patients.

Single-cell profiling of the microenvironment in human bone metastatic renal cell carcinoma.

Bone metastasis is of common occurrence in renal cell carcinoma with poor prognosis, but no optimal treatment approach has been established for bone metastatic renal cell carcinoma. To explore the potential therapeutic targets for bone metastatic renal cell carcinoma, we profile single cell transcriptomes of 6 primary renal cell carcinoma and 9 bone metastatic renal cell carcinoma. We also include scRNA-seq data of early-stage renal cell carcinoma, late-stage renal cell carcinoma, normal kidneys and healthy bone marrow samples in the study to better understand the bone metastasis niche. The molecular properties and dynamic changes of major cell lineages in bone metastatic environment of renal cell carcinoma are characterized. Bone metastatic renal cell carcinoma is associated with multifaceted immune deficiency together with cancer-associated fibroblasts, specifically appearance of macrophages exhibiting malignant and pro-angiogenic features. We also reveal the dominance of immune inhibitory T cells in the bone metastatic renal cell carcinoma which can be partially restored by the treatment. Trajectory analysis showes that myeloid-derived suppressor cells are progenitors of macrophages in the bone metastatic renal cell carcinoma while monocytes are their progenitors in primary tumors and healthy bone marrows. Additionally, the infiltration of immune inhibitory CD47+ T cells is observed in bone metastatic tumors, which may be a result of reduced phagocytosis by SIRPA-expressing macrophages in the bone microenvironment. Together, our results provide a systematic view of various cell types in bone metastatic renal cell carcinoma and suggest avenues for therapeutic solutions.

Preclinical Evaluation and a Pilot Clinical Positron Emission Tomography Imaging Study of [68Ga]Ga-FAPI-FUSCC-II.

Fibroblast activation protein (FAP), a type II integral membrane serine protease, is a promising target for tumor diagnosis and therapy. OncoFAP has been recently discovered for PET imaging procedures for various solid malignancies. In this study, we presented the development of manual radiolabeling procedures for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging. A novel series of [68Ga/177Lu]Ga/Lu-FAPI-FUSCC-I/II were produced with high radiochemical yields. [68Ga]Ga-FAPI-FUSCC-I/II and [177Lu]Lu-FAPI-FUSCC-I/II were stable in phosphate-buffered saline, fetal bovine serum, and human serum for at least 3 h. In vitro cellular uptake and blocking experiments implied that they had specificity to FAP. Additionally, the low nanomolar IC50 values of FAPI-FUSCC-II indicated that it had a high target affinity to FAP. The in vivo biodistribution and blocking study in mice bearing HT-1080-FAP tumors showed that both exhibited specific tumor uptake. [68Ga]Ga-FAPI-FUSCC-II showed a higher tumor uptake and a higher tumor/nontarget ratio than [68Ga]Ga-FAPI-FUSCC-I and [68Ga]Ga-FAPI-04. The results of ex vivo biodistribution were in accordance with the biodistribution results. Clinical [68Ga]Ga-FAPI-FUSCC-II-PET/CT imaging further demonstrated its favorable biodistribution and kinetics with elevated and reliable uptake by primary tumors (maximum standardized uptake value (SUVmax), 12.17 ± 6.67) and distant metastases (SUVmax, 9.24 ± 4.28). In summary, [68Ga]Ga-FAPI-FUSCC-II displayed increased tumor uptake and retention compared to [68Ga]Ga-FAPI-04, giving it potential as a promising tracer for the diagnostic imaging of malignant tumors with positive FAP expression.

Differentiation of cancer of unknown primary and lymphoma in head and neck metastatic poorly differentiated cancer using 18 F-FDG PET/CT tumor metabolic heterogeneity index.

OBJECTIVE: To explore the value of 18 F-FDG PET/CT tumor metabolic heterogeneity index (HI) and establish and validate a nomogram model for distinguishing head and neck cancer of unknown primary (HNCUP) from lymphoma with head and neck metastatic poorly differentiated cancer. METHODS: This retrospective analysis was conducted on 1242 patients with cervical metastatic poorly differentiated cancer. 108 patients, who were clinically and pathologically confirmed as HNCUP or lymphoma, were finally enrolled. Two independent sample t-tests and χ 2 test were used to compare the clinical and imaging features. Binary logistic regression was used to screen for independent predictive factors. RESULTS: Among the 108 patients), 65 patients were diagnosed with HNCUP and 43 were lymphoma. Gender ( P  = 0.001), SUV max ( P  < 0.001), SUV mean ( P  < 0.001), TLG ( P  = 0.012), and HI ( P  < 0.001) had statistical significance in distinguishing HNCUP and lymphoma. Female ( OR  = 4.546, P  = 0.003) and patients with HI ≥ 2.37 ( OR  = 3.461, P  = 0.047) were more likely to be diagnosed as lymphoma. CONCLUSION: For patients with cervical metastatic poorly differentiated cancer, gender and HI were independent predictors of pathological type. For such patients, clinical attention should be paid to avoid misdiagnosing lymphoma as HNCUP, which may delay treatment.

Pretreatment 18F-FDG uptake heterogeneity may predict treatment outcome of combined Trastuzumab and Pertuzumab therapy in patients with metastatic HER2 positive breast cancer.

OBJECTIVE: Intra-tumoral heterogeneity of 18F-fluorodeoxyglucose (18F-FDG) uptake has been proven to be a surrogate marker for predicting treatment outcome in various tumors. However, the value of intra-tumoral heterogeneity in metastatic Human epidermal growth factor receptor 2(HER2) positive breast cancer (MHBC) remains unknown. The aim of this study was to evaluate 18F-FDG uptake heterogeneity to predict the treatment outcome of the dual target therapy with Trastuzumab and Pertuzumab(TP) in MHBC. METHODS: Thirty-two patients with MHBC who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) scan before TP were enrolled retrospectively. The region of interesting (ROI) of the lesions were drawn, and maximum standard uptake value (SUVmax), mean standard uptake value (SUVmean), total lesion glycolysis (TLG), metabolic tumor volume (MTV) and heterogeneity index (HI) were recorded. Correlation between PET/CT parameters and the treatment outcome was analyzed by Spearman Rank Test. The ability to predict prognosis were determined by time-dependent survival receiver operating characteristic (ROC) analysis. And the survival analyses were then estimated by Kaplan-Meier method and compared by log-rank test. RESULTS: The survival analysis showed that HI50% calculated by delineating the lesion with 50%SUVmax as threshold was a significant predictor of patients with MHBC treated by the treatment with TP. Patients with HI50% (≥ 1.571) had a significantly worse prognosis of progression free survival (PFS) (6.87 vs. Not Reach, p = 0.001). The area under curve (AUC), the sensitivity and the specificity were 0.88, 100% and 63.6% for PFS, respectively. CONCLUSION: 18F-FDG uptake heterogeneity may be useful for predicting the prognosis of MHBC patients treated by TP.

Multi-task deep learning-based radiomic nomogram for prognostic prediction in locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: Prognostic prediction is crucial to guide individual treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients. Recently, multi-task deep learning was explored for joint prognostic prediction and tumor segmentation in various cancers, resulting in promising performance. This study aims to evaluate the clinical value of multi-task deep learning for prognostic prediction in LA-NPC patients. METHODS: A total of 886 LA-NPC patients acquired from two medical centers were enrolled including clinical data, [18F]FDG PET/CT images, and follow-up of progression-free survival (PFS). We adopted a deep multi-task survival model (DeepMTS) to jointly perform prognostic prediction (DeepMTS-Score) and tumor segmentation from FDG-PET/CT images. The DeepMTS-derived segmentation masks were leveraged to extract handcrafted radiomics features, which were also used for prognostic prediction (AutoRadio-Score). Finally, we developed a multi-task deep learning-based radiomic (MTDLR) nomogram by integrating DeepMTS-Score, AutoRadio-Score, and clinical data. Harrell's concordance indices (C-index) and time-independent receiver operating characteristic (ROC) analysis were used to evaluate the discriminative ability of the proposed MTDLR nomogram. For patient stratification, the PFS rates of high- and low-risk patients were calculated using Kaplan-Meier method and compared with the observed PFS probability. RESULTS: Our MTDLR nomogram achieved C-index of 0.818 (95% confidence interval (CI): 0.785-0.851), 0.752 (95% CI: 0.638-0.865), and 0.717 (95% CI: 0.641-0.793) and area under curve (AUC) of 0.859 (95% CI: 0.822-0.895), 0.769 (95% CI: 0.642-0.896), and 0.730 (95% CI: 0.634-0.826) in the training, internal validation, and external validation cohorts, which showed a statistically significant improvement over conventional radiomic nomograms. Our nomogram also divided patients into significantly different high- and low-risk groups. CONCLUSION: Our study demonstrated that MTDLR nomogram can perform reliable and accurate prognostic prediction in LA-NPC patients, and also enabled better patient stratification, which could facilitate personalized treatment planning.

PET imaging of PARP expression using 68Ga-labelled inhibitors.

PURPOSE: Imaging the PARP expression using 18F probes has been approved in clinical trials. Nevertheless, hepatobiliary clearance of both 18F probes hindered their application in monitoring abdominal lesions. Our novel 68Ga-labelled probes aim for fewer abdominal signals while ensuring PARP targeting by optimizing the pharmacokinetic properties of radioactive probes. METHODS: Three radioactive probes targeted PARP were designed, synthesized, and evaluated based on the PARP inhibitor Olaparib. These 68Ga-labelled radiotracers were assessed in vitro and in vivo. RESULTS: Precursors that did not lose binding affinity for PARP were designed, synthesized, and then labelled with 68Ga in high radiochemical purity (> 97%). The 68Ga-labelled radiotracers were stable. Due to the increased expression of PARP-1 in SK-OV-3 cells, the uptake of the three radiotracers by SK-OV-3 cells was significantly greater than that by A549 cells. PET/CT imaging of the SK-OV-3 models indicated that the tumor uptake of 68Ga-DOTA-Olaparib (0.5 h: 2.83 ± 0.55%ID/g; 1 h: 2.37 ± 0.64%ID/g) was significantly higher than that of the other 68Ga-labelled radiotracers. There was a significant difference in the T/M (tumor-to-muscle) ratios between the unblocked and blocked groups as calculated from the PET/CT images (4.07 ± 1.01 vs. 1.79 ± 0.45, P = 0.0238 < 0.05). Tumor autoradiography revealed high accumulation in tumor tissues, further confirming the above data. PARP-1 expression in the tumor was confirmed by immunochemistry. CONCLUSION: As the first 68Ga-labelled PARP inhibitor, 68Ga-DOTA-Olaparib displayed high stability and quick PARP imaging in a tumor model. This compound is thus a promising imaging agent that can be used in a personalized PARP inhibitor treatment regimen.

In situ forming oxygen/ROS-responsive niche-like hydrogel enabling gelation-triggered chemotherapy and inhibition of metastasis.

Though the development of the diverse hypoxia-activated prodrugs (HAPs) has made great progresses in the last several decades, current cancer therapy based on HAPs still suffers many obstacles, e.g., poor therapeutic outcome owing to hard deep reaching to hypoxic region, and the occurrence of metastasis due to hypoxia. Inspired by engineered niches, a novel functional chitosan polymer (CS-FTP) is synthesized for construction of a hydrogel-based bio-niche (CS-FTP-gel) in aiming at remodeling tumor hypoxic microenvironment. The CS-FTP polymers are crosslinked to form a niche-like hydrogel via enzyme-mediated oxygen-consumable dimerization after injected into tumor, in which a HAP (i.e., AQ4N) could be physically encapsulated, resulting in enhanced tumor hypoxia to facilitate AQ4N-AQ4 toxic transformation for maximizing efficacy of chemotherapy. Furthermore, Pazopanib (PAZ) conjugated onto the CS backbone via ROS-sensitive linker undergoes a stimuli-responsive release behavior to promote antiangiogenesis for tumor starvation, eventually contributing to the inhibition of lung metastasis and synergistic action with AQ4N-based chemotherapy for an orthotopic 4T1 breast tumor model. This study provides a promising strategy for hypoxia-based chemotherapy and demonstrates an encouraging clinical potential for multifunctional hydrogel applicable for antitumor treatment.

Prediction of 5-year progression-free survival in advanced nasopharyngeal carcinoma with pretreatment PET/CT using multi-modality deep learning-based radiomics.

Objective: Deep learning-based radiomics (DLR) has achieved great success in medical image analysis and has been considered a replacement for conventional radiomics that relies on handcrafted features. In this study, we aimed to explore the capability of DLR for the prediction of 5-year progression-free survival (PFS) in advanced nasopharyngeal carcinoma (NPC) using pretreatment PET/CT images. Methods: A total of 257 patients (170/87 patients in internal/external cohorts) with advanced NPC (TNM stage III or IVa) were enrolled. We developed an end-to-end multi-modality DLR model, in which a 3D convolutional neural network was optimized to extract deep features from pretreatment PET/CT images and predict the probability of 5-year PFS. The TNM stage, as a high-level clinical feature, could be integrated into our DLR model to further improve the prognostic performance. For a comparison between conventional radiomics and DLR, 1,456 handcrafted features were extracted, and optimal conventional radiomics methods were selected from 54 cross-combinations of six feature selection methods and nine classification methods. In addition, risk group stratification was performed with clinical signature, conventional radiomics signature, and DLR signature. Results: Our multi-modality DLR model using both PET and CT achieved higher prognostic performance (area under the receiver operating characteristic curve (AUC) = 0.842 ± 0.034 and 0.823 ± 0.012 for the internal and external cohorts) than the optimal conventional radiomics method (AUC = 0.796 ± 0.033 and 0.782 ± 0.012). Furthermore, the multi-modality DLR model outperformed single-modality DLR models using only PET (AUC = 0.818 ± 0.029 and 0.796 ± 0.009) or only CT (AUC = 0.657 ± 0.055 and 0.645 ± 0.021). For risk group stratification, the conventional radiomics signature and DLR signature enabled significant difference between the high- and low-risk patient groups in both the internal and external cohorts (p < 0.001), while the clinical signature failed in the external cohort (p = 0.177). Conclusion: Our study identified potential prognostic tools for survival prediction in advanced NPC, which suggests that DLR could provide complementary values to the current TNM staging.

DeepMTS: Deep Multi-Task Learning for Survival Prediction in Patients With Advanced Nasopharyngeal Carcinoma Using Pretreatment PET/CT.

Nasopharyngeal Carcinoma (NPC) is a malignant epithelial cancer arising from the nasopharynx. Survival prediction is a major concern for NPC patients, as it provides early prognostic information to plan treatments. Recently, deep survival models based on deep learning have demonstrated the potential to outperform traditional radiomics-based survival prediction models. Deep survival models usually use image patches covering the whole target regions (e.g., nasopharynx for NPC) or containing only segmented tumor regions as the input. However, the models using the whole target regions will also include non-relevant background information, while the models using segmented tumor regions will disregard potentially prognostic information existing out of primary tumors (e.g., local lymph node metastasis and adjacent tissue invasion). In this study, we propose a 3D end-to-end Deep Multi-Task Survival model (DeepMTS) for joint survival prediction and tumor segmentation in advanced NPC from pretreatment PET/CT. Our novelty is the introduction of a hard-sharing segmentation backbone to guide the extraction of local features related to the primary tumors, which reduces the interference from non-relevant background information. In addition, we also introduce a cascaded survival network to capture the prognostic information existing out of primary tumors and further leverage the global tumor information (e.g., tumor size, shape, and locations) derived from the segmentation backbone. Our experiments with two clinical datasets demonstrate that our DeepMTS can consistently outperform traditional radiomics-based survival prediction models and existing deep survival models.

Prognostic Value of Heterogeneity Index Derived from Baseline 18F-FDG PET/CT in Mantle Cell Lymphoma.

Objectives: Mantle cell lymphoma (MCL) represents a group of highly heterogeneous tumors, leading to a poor prognosis. Early prognosis prediction may guide the choice of therapeutic regimen. Thus, the purpose of this study was to investigate the potential application value of heterogeneity index (HI) in predicting the prognosis of MCL. Methods: A total of 83 patients with histologically proven MCL who underwent baseline fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were retrospectively enrolled. The clinicopathologic index and PET/CT metabolic parameters containing maximum and mean standard uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and HI were evaluated. Receiver operating characteristic (ROC) curve analyses were performed to determine the optimal cutoff values of the parameters for progression-free survival (PFS) and overall survival (OS). Univariate and multivariate Cox regression were used to assess relationships between risk factors and recurrence. Kaplan-Meier plots were applied for survival analyses. Results: In univariate analyses, age [HR = 2.51, 95% CI = 1.20-5.24, p = 0.041 for body weight (BW)] and HI-BW (HR = 4.17, 95% CI = 1.00-17.38, p = 0.050) were significantly correlated with PFS. In multivariate analyses, age (HR = 2.61, 95% CI = 1.25-5.47, p = 0.011 for BW) and HI-BW (HR = 4.41, 95% CI = 1.06-18.41, p = 0.042) were independent predictors for PFS, but not for OS. B symptoms (HR = 5.00, 95% CI = 1.16-21.65, p = 0.031 for BW) were an independent prognostic factor for OS, but not for PFS. The other clinicopathologic index and PET/CT metabolic parameters were not related to outcome survival in MCL. Conclusion: The age and HI derived from baseline PET/CT parameters were significantly correlated with PFS in MCL patients.

Head-to-head evaluation of [18F]FDG and [68 Ga]Ga-DOTA-FAPI-04 PET/CT in recurrent soft tissue sarcoma.

PURPOSE: We aimed to evaluate the value of [68 Ga]Ga-DOTA-FAPI-04 PET/CT for the diagnosis of recurrent soft tissue sarcoma (STS), compared with [18F]FDG PET/CT. METHODS: A total of 45 patients (21 females and 24 males; median age, 46 years; range, 18-71 years) with 13 subtypes of STS underwent [18F]FDG and [68 Ga]Ga-DOTA-FAPI-04 PET/CT examination within 1 week for assessment local relapse or distant metastasis. Positive lesions on PET/CT images were verified by biopsy or 3-month follow-up. Wilcoxon matched-pairs signed-rank test was used to compare the semiquantitative values (SUVmax and TBR) of [18F]FDG and [68 Ga]Ga-DOTA-FAPI-04 in tumor lesions, and McNemar test was applied to test for differences of both tracers. RESULTS: Among the 45 patients, 282 local relapses and distant metastases were identified. Compared to [18F]FDG, [68 Ga]Ga-DOTA-FAPI-04 PET/CT detected more lesions (275 vs. 186) and outperformed in sensitivity, specificity, PPV, NPV, and accuracy for the diagnosis of recurrent lesions (P < 0.001). [68 Ga]Ga-DOTA-FAPI-04 demonstrated significantly higher values of SUVmax and TBR than [18F]FDG PET/CT in liposarcoma (P = 0.011 and P < 0.001, respectively), malignant solitary fibrous tumor (MSFT) (P < 0.001 and P < 0.001, respectively), and interdigitating dendritic cell sarcoma (IDCS) (P < 0.001and P < 0.001, respectively). While mean SUVmax and TBR presented favorable uptake of [18F]FDG over [68 Ga]Ga-DOTA-FAPI-04 in undifferentiated pleomorphic sarcoma (UPS) (P = 0.003 and P < 0.001, respectively) and rhabdomyosarcoma (RMS) (P < 0.001 and P < 0.001, respectively). CONCLUSION: [68 Ga]Ga-DOTA-FAPI-04 PET/CT is a promising new imaging modality for recurrent surveillance of STS, and compares favorably with [18F]FDG for identifying recurrent lesions of liposarcoma, MSFT, and IDCS.

The Added Value of 68Ga-FAPI PET/CT in Patients with Head and Neck Cancer of Unknown Primary with 18F-FDG-Negative Findings.

18F-FDG PET/CT plays an important role in locating the primary tumor for patients with head and neck cancer of unknown primary (HNCUP). Nevertheless, in some cases it can be challenging to locate the primary malignancy on 18F-FDG PET/CT scans. Because 68Ga-radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT has promising results in detecting different tumor entities, our study aimed to evaluate the performance of 68Ga-FAPI PET/CT for detecting the primary tumor in HNCUP patients with negative 18F-FDG findings. Methods: Eighteen patients (16 men and 2 women; median age, 55 y; age range, 24-72 y) with negative 18F-FDG findings were enrolled in this study. All patients underwent 18F-FDG and 68Ga-FAPI PET/CT within 1 wk. Biopsy and histopathologic examinations were performed in the sites with positive 68Ga-FAPI PET/CT findings. Results:68Ga-FAPI PET/CT detected the primary tumor in 7 of 18 patients (38.89%). Among these 7 patients, primary tumor sites included the nasopharynx (n = 1), palatine tonsil (n = 2), submandibular gland (n = 2), and hypopharynx (n = 2). The primary tumors showed moderate to intensive uptake of 68Ga-FAPI (mean SUVmax, 8.79; range, 2.60-16.50) and excellent tumor-to-contralateral normal-tissue ratio (mean SUVmax ratio, 4.50; range, 2.17-8.21). In lesion-based analysis, 65 lymph nodes and 17 bone metastatic lesions were identified. The mean SUVmax of lymph node metastases was 9.05 ± 5.29 for 18F-FDG and 9.08 ± 4.69 for 68Ga-FAPI (P = 0.975); the mean SUVmax of bone metastases was 8.11 ± 3.00 for 18F-FDG and 6.96 ± 5.87 for 68Ga-FAPI (P = 0.478). The mean tumor-to-background ratios of lymph node and bone metastases were 10.65 ± 6.59 versus 12.80 ± 8.11 (P = 0.100) and 9.08 ± 3.35 versus 9.14 ± 8.40 (P = 0.976), respectively. Conclusion: We present the first evidence, to our knowledge, of a diagnostic role of 68Ga-FAPI PET/CT in HNCUP. Our study demonstrated that 68Ga-FAPI PET/CT has the potential to improve the detection rate of primary tumor in HNCUP patients with negative 18F-FDG findings. Moreover, 68Ga-FAPI had a performance in assessing metastases similar to that of 18F-FDG.

A core-shell Au@Cu2-xSe heterogeneous metal nanocomposite for photoacoustic and computed tomography dual-imaging-guided photothermal boosted chemodynamic therapy.

Chemodynamic therapy (CDT) has aroused extensive attention for conquering cancers because of its high specificity and low invasiveness. Quick generation of hydroxyl radicals (·OH) during CDT could induce more irreparable damage to cancer cells. The generation rate of ·OH could be magnified via the selection of suitable nanocatalysts or under the assistance of exogenous thermal energy from photothermal therapy (PTT). Here, we construct a kind of monodisperse core-shell Au@Cu2-xSe heterogeneous metal nanoparticles (NPs) for PTT boosted CDT synergistic therapy. Due to the localized surface plasmon resonance (LSPR) coupling effect in the core-shell structure, the photothermal conversion efficiency of Au@Cu2-xSe NPs is up to 56.6%. The in situ generated heat from photothermal can then accelerate the Fenton-like reaction at Cu+ sites to produce abundant ·OH, which will induce apoptotic cell death by attacking DNA, contributing to a heat-boosted CDT. Both in vitro and in vivo results showed that after this synergistic therapy, tumors could be remarkably suppressed. Guided by photoacoustic (PA) and computed tomography (CT) imaging, the therapeutic effects were more specified. Our results revealed that PA and CT dual-imaging-guided PTT boosted CDT synergistic therapy based on core-shell Au@Cu2-xSe NPs is an effective cancer treatment strategy.

Superfast Water Transport Zwitterionic Polymeric Nanofluidic Membrane Reinforced by Metal-Organic Frameworks.

Nanofluidics derived from low-dimensional nanosheets and protein nanochannels are crucial for advanced catalysis, sensing, and separation. However, polymer nanofluidics is halted by complicated preparation and miniaturized sizes. This work reports the bottom-up synthesis of modular nanofluidics by confined growth of ultrathin metal-organic frameworks (MOFs) in a polymer membrane consisting of zwitterionic dopamine nanoparticles (ZNPs). The confined growth of the MOFs on the ZNPs reduces the chain entanglement between the ZNPs, leading to stiff interfacial channels enhancing the nanofluidic transport of water molecules through the membrane. As such, the water permeability and solute selectivity of MOF@ZNPM are one magnitude improved, leading to a record-high performance among all polymer nanofiltration membranes. Both the experimental work and the molecular dynamics simulations confirm that the water transport is shifted from high-friction-resistance conventional viscous flow to ultrafast nanofluidic flow as a result of rigid and continuous nanochannels in MOF@ZNPM.

A Novel Validated Recurrence Stratification System Based on 18F-FDG PET/CT Radiomics to Guide Surveillance After Resection of Pancreatic Cancer.

OBJECTIVE: Despite the heterogeneous biology of pancreatic cancer, similar surveillance schemas have been used. Identifying the high recurrence risk population and conducting prompt intervention may improve prognosis and prolong overall survival. METHODS: One hundred fifty-six resectable pancreatic cancer patients who had undergone 18F-FDG PET/CT from January 2013 to December 2018 were retrospectively reviewed. The patients were categorized into a training cohort (n = 109) and a validation cohort (n = 47). LIFEx software was used to extract radiomic features from PET/CT. The risk stratification system was based on predictive factors for recurrence, and the index of prediction accuracy was used to reflect both the discrimination and calibration. RESULTS: Overall, seven risk factors comprising the rad-score and clinical variables that were significantly correlated with relapse were incorporated into the final risk stratification system. The 1-year recurrence-free survival differed significantly among the low-, intermediate-, and high-risk groups (85.5, 24.0, and 9.1%, respectively; p < 0.0001). The C-index of the risk stratification system in the development cohort was 0.890 (95% CI, 0.835-0.945). CONCLUSION: The 18F-FDG PET/CT-based radiomic features and clinicopathological factors demonstrated good performance in predicting recurrence after pancreatectomy in pancreatic cancer patients, providing a strong recommendation for an adequate adjuvant therapy course in all patients. The high-risk recurrence population should proceed with closer follow-up in a clinical setting.

Pretreatment 18F-FDG uptake heterogeneity can predict treatment outcome of carbon ion radiotherapy in patients with locally recurrent nasopharyngeal carcinoma.

OBJECTIVE: Our study was to investigate the value of pretreatment 18F-FDG uptake heterogeneity to predict the prognosis of patients with locally recurrent nasopharyngeal carcinoma (LRNPC) treated by carbon ion radiotherapy (CIRT). METHODS: Twenty-nine LRNPC patients who underwent whole-body 18F-FDG PET/CT scanning before CIRT were enrolled. Heterogeneity index (HI)-based 18F-FDG uptake, and the PET/CT traditional parameters, including SUVmax, MTV, and TLG were assessed. Receiver operator characteristics (ROC) determined the best cutoff value, and local recurrence-free survival (LRFS) and progression-free survival (PFS) were evaluated by the Kaplan-Meier method and log-rank test. And the predictive ability was evaluated by the ROC curve. Cox analyses were performed on LRFS and PFS. RESULTS: In this study, univariate analysis showed that HI was a significant predictor of LRNPC treated by CIRT. HI could be used to predict LRFS and PFS. Patients with HI (≥ 0.81) had a significantly worse prognosis of LRFS (12.25 vs. NR, p = 0.008), and of PFS (10.58 vs. NR, p = 0.014). The AUC and its sensitivity and sensitivity and specificity were 0.75, 84.21% and 70.00% for LRFS and 0.82, 80.95% and 75.00% for PFS, respectively. Multivariate analysis showed that HI was an independent predictor for the LFRS of LRNPC with CIRT. CONCLUSION: 18F-FDG uptake heterogeneity may be useful for predicting the prognosis of patients with LRNPC treated by CIRT.

A pH-responsive photoacoustic imaging probe for tumor pH imaging in vivo based on polyaniline-bovine serum albumin.

Precise pH detection in tumors can guide the design of pH-responsive drugs and theranostic agents to improve treatment efficacy. However, most reported pH-responsive probes are fluorescent probes, for which in vivo application is limited by low probe penetration depth. In this study, a pH-responsive polyaniline-bovine serum albumin (BSA) probe was constructed for precise pH detection in tumors using photoacoustic imaging. The probe can be used to generate high-resolution images of deep biological tissues. The photoacoustic signal of the polyaniline-BSA probe exhibits a clear linear relationship with pH in the range of 5-6.8 both in vitro and in vivo, indicating that the probe is ideal for precise pH detection in most tumors. The polyaniline-BSA probe also exhibits satisfactory biocompatibility, low toxicity, fast response, and good reversibility. This work provides a useful in vivo pH detection probe for developing pH-responsive drugs and theranostic agents.

68Ga-FAPI and 18F-FDG PET/CT Images in a Patient With Extrapulmonary Tuberculosis Mimicking Malignant Tumor.

Extrapulmonary tuberculosis (TB) is difficult to diagnose. Here, we report a case of extrapulmonary TB in a 68-year-old woman presented with mental fatigue, poor appetite, and weight loss. F-FDG PET/CT revealed elevated F-FDG uptake in the left inferior cervical, left supraclavicular, mediastinal, and splenic hilum lymph nodes and spleen, which were suspected of malignant tumor. To further differentiate benign and malignant diseases, Ga-FAPI PET/CT was performed. Ga-FAPI PET/CT also showed intense Ga-FAPI uptake in the previously mentioned FDG-avid lesions. However, biopsy of the left supraclavicular lymph node demonstrated the presence of TB.