Efficacy and Safety Evaluation of 177Lu-FAP-2286 in the Treatment of Advanced Lung Cancer.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of peptide-targeted radionuclide therapy (PTRT) with 177Lu-FAP-2286 in advanced lung cancer. PATIENTS AND METHODS: This single-center prospective study included 9 patients diagnosed with advanced lung cancer. These patients met the inclusion criteria and received PTRT with 177Lu-FAP-2286. Short-term efficacy was assessed using RECIST 1.1 and PERCIST 1.0 criteria. Long-term efficacy was evaluated through overall survival, progression-free survival (PFS), overall response rate, EORTC QLQ-C30 v3.0, Eastern Cooperative Oncology Group, and Karnofsky Performance Status. Toxicity response was assessed using CTCAE v5.0. RESULTS: The results based on RECIST 1.1 and PERCIST 1.0 criteria were comparable, with 44% of patients showing a partial metabolic response, 33.3% with stable metabolic disease, and 22.22% with progressive metabolic disease. The highest metabolic response after treatment reached 66.89%, and the overall response rate could reach 77.78%. In the long-term efficacy assessment, the median overall survival and PFS were 10 months and 6 months, respectively. The 2 patients with the lowest PFS (3 months) started PTRT relatively late. EORTC QLQ-C30 v3.0, Eastern Cooperative Oncology Group, and Karnofsky Performance Status scores showed that the overall health status, symptom response, and quality of life of patients improved after 177Lu-FAP-2286 treatment. The most noticeable improvements in clinical symptoms were dyspnea and cancer-related pain. No grade III/IV toxicity events were observed during follow-up period, and fibrinogen decreased significantly after treatment. CONCLUSIONS: 177Lu-FAP-2286 has the potential to be a viable PTRT option for patients with advanced lung cancer.

Elevated 68Ga-FAPI Activity in Benign Carotid Body Tumors.

ABSTRACT: We present 68Ga-FAPI PET/CT findings of benign carotid body tumor in a 33-year-old woman. Benign carotid body tumor demonstrated intense tracer uptakes on 68Ga-FAPI PET/CT. Our case suggests that benign carotid body tumors should be considered in the differential diagnosis of neck mass with elevated 68Ga-FAPI activity.

Dynamic changes and correlation analysis of microorganisms and flavonoids/ amino acids during white tea storage.

White tea stored for various times have different flavors. However, the mechanism of flavor conversion remains elusive. Flavonoids and amino acids are two typical flavor components in tea. Herein, the contents of 46 flavonoids and 40 amino acids were measured in white tea (Shoumei) stored for 1, 3, 5 and 7 years, respectively. L-tryptophan, L-ornithine and L-theanine contribute to the refreshing taste of Shoumei 1 and 3. Quercetin, rutin and hesperidin contribute to aging charm and grain aroma of Shoumei 5 and 7. 306 bacterial OTUs and 268 fungal OTUs core microbiota existed in all samples. Interestingly, white teas contained higher richness of fungi than bacteria. The correlation analysis showed that the cooperation with bacteria and fungi may result in the flavonoids and amino acids composition changes in white teas during storage. Overall, this study provides new insights into flavor conversion of white tea during storage.

Elevated 68 Ga-FAPI Activity in Pulmonary Inflammatory Pseudotumor.

ABSTRACT: We present a case of pulmonary inflammatory pseudotumor with elevated 68 Ga-FAPI activity. Our case suggested that pulmonary inflammatory pseudotumor should be considered in the differential diagnosis of cancer-like solitary pulmonary nodules with increased 68 Ga-FAPI uptake.

A retrospective study of 68Ga-FAPI PET/CT in differentiating the nature of pulmonary lesions.

Purpose: This study aimed to investigate the characteristics of various pulmonary lesions as revealed by 68Ga-FAPI PET/CT and to determine the utility of 68Ga-FAPI PET/CT in distinguishing the nature of these pulmonary lesions. Methods: A retrospective analysis was conducted on 99 patients with pulmonary lesions, who were categorized into three distinct groups: primary lung tumors (G1), metastatic lung tumors (G2), and benign lesions (G3). Each participant underwent a 68Ga-FAPI PET/CT scan. Among these groups, variables such as the Tumor/Background Ratio (TBR), Maximum Standardized Uptake Value (SUVmax), and the true positive rate of the lesions were compared. Furthermore, the FAPI uptake in nodular-like pulmonary lesions (d<3cm) and those with irregular borders was evaluated across the groups. A correlation analysis sought to understand the relationship between FAPI uptake in primary and pulmonary metastatic lesions. Results: The study's participants were composed of 52 males and 47 females, with an average age of 56.8 ± 13.2 years. A higher uptake and detection rate for pulmonary lesions were exhibited by Group G1 compared to the other groups (SUVmax [G1 vs. G2 vs. G3: 9.1 ± 4.1 vs. 6.1 ± 4.1 vs. 5.3 ± 5.8], P<0.05; TBR [G1 vs. G2 vs. G3: 6.2 ± 2.4 vs. 4.1 ± 2.2 vs. 3.2 ± 2.7], P<0.01; true positive rate 95.1% vs. 88% vs. 75.6%]. In nodular-like lung lesions smaller than 3 cm, G1 showed a significantly higher FAPI uptake compared to G2 and G3 (SUVmax [G1 vs. G2 vs. G3: 8.8 ± 4.3 vs. 5.2 ± 3.2 vs. 4.9 ± 6.1], P<0.01; TBR [G1 vs. G2 vs. G3: 5.7 ± 2.7 vs. 3.7 ± 2.1 vs. 3.3 ± 4.4], P<0.05). Both G1 and G2 demonstrated significantly elevated FAPI agent activity in irregular-bordered pulmonary lesions when compared to G3 (SUVmax [G1 vs. G2 vs. G3: 10.9 ± 3.3 vs. 8.5 ± 2.7 vs. 4.6 ± 2.7], P<0.01; TBR [G1 vs. G2 vs. G3: 7.2 ± 2.1 vs. 6.4 ± 1.3 vs. 3.2 ± 2.4], P<0.01). A positive correlation was identified between the level of 68Ga-FAPI uptake in primary lesions and the uptake in pulmonary metastatic lesions within G2 (r=0.856, P<0.05). Conclusion: 68Ga-FAPI PET/CT imaging proves to be of significant value in the evaluation of pulmonary lesions, offering distinctive insights into their nature.

Elevated FAPI Activity in an Adult Brodie Abscess.

ABSTRACT: We report an adult Brodie abscess with elevated activity of 18 F-FDG and 68 Ga-FAPI (fibroblast activating protein inhibitor), mimicking bone metastasis. Our case illustrates that Brodie abscess should also be contemplated in the differential diagnosis of osteolytic lesions with increased 68 Ga-FAPI uptake.

Elevated 68 Ga-FAPI Activity in Klebsiella pneumoniae Invasion Syndrome.

ABSTRACT: Klebsiella pneumoniae invasion syndrome is a rare disease associated with primary liver abscess and secondary extrahepatic infection. We report a case of K. pneumoniae invasion syndrome with elevated 68 Ga-FAPI uptake, mimicking malignancy with multiple metastases. Our case illustrated that K. pneumoniae invasion syndrome should be considered as a possible etiology when diagnosing multiple 68 Ga-FAPI-avid liver foci with metastatic lesions. Besides, PET/CT could be an integrated tool to search for systemic occult lesions in K. pneumoniae invasion syndrome.

Elevated FAPI Activity in Ulcerative Fungal Esophagitis.

ABSTRACT: We report a case of ulcerative fungal esophagitis with elevated activity of 18 F-FDG and 68 Ga-FAPI (fibroblast-activating protein inhibitor). Our findings suggest that ulcerative fungal esophagitis should be considered in the differential diagnosis of cancer-like esophageal mass with increased 68 Ga-FAPI uptake.

Schmorl Node Can Cause Increased 68Ga-FAPI Activity on PET/CT.

ABSTRACT: 68Ga-FAPI is a newly developed tumor imaging agent with promising clinical applications. However, benign lesions may also show increased FAPI activity. We accidentally discovered that Schmorl node expressed FAPI activity in a patient with sweat gland cancer. Thus, greater awareness is needed that Schmorl nodes are a potential reason for false-positive uptake on 68Ga-FAPI PET/CT.

Non-18F-FDG-Avid Intrahepatic Metastasis of Breast Cancer Revealed by 68Ga-FAPI PET/CT.

ABSTRACT: A patient with intrahepatic breast cancer metastasis underwent both 18F-FDG and 68Ga-FAPI PET/CT. However, the lesions are only 68Ga-FAPI avid. Our case illustrates that 68Ga-FAPI PET/CT can be more sensitive in detecting intrahepatic metastasis of breast cancer in some cases.

Organizing Pneumonia With Intense 68Ga-FAPI Uptake Mimicking Lung Cancer on 68Ga-FAPI PET/CT.

ABSTRACT: We report a case of organizing pneumonia, which revealed intense uptake on both 18F-FDG and 68Ga-FAPI (fibroblast activation protein inhibitor) PET/CT. Our findings indicate that organizing pneumonia should be taken into consideration when diagnosing a cancer-like pulmonary mass with intense 68Ga-FAPI uptake.

TMK-based cell-surface auxin signalling activates cell-wall acidification.

The phytohormone auxin controls many processes in plants, at least in part through its regulation of cell expansion1. The acid growth hypothesis has been proposed to explain auxin-stimulated cell expansion for five decades, but the mechanism that underlies auxin-induced cell-wall acidification is poorly characterized. Auxin induces the phosphorylation and activation of the plasma membrane H+-ATPase that pumps protons into the apoplast2, yet how auxin activates its phosphorylation remains unclear. Here we show that the transmembrane kinase (TMK) auxin-signalling proteins interact with plasma membrane H+-ATPases, inducing their phosphorylation, and thereby promoting cell-wall acidification and hypocotyl cell elongation in Arabidopsis. Auxin induced interactions between TMKs and H+-ATPases in the plasma membrane within seconds, as well as TMK-dependent phosphorylation of the penultimate threonine residue on the H+-ATPases. Our genetic, biochemical and molecular evidence demonstrates that TMKs directly phosphorylate plasma membrane H+-ATPase and are required for auxin-induced H+-ATPase activation, apoplastic acidification and cell expansion. Thus, our findings reveal a crucial connection between auxin and plasma membrane H+-ATPase activation in regulating apoplastic pH changes and cell expansion through TMK-based cell surface auxin signalling.

68Ga-DOTA-FAPI-04 PET/CT as a Promising Tool for Differentiating Ovarian Physiological Uptake: Preliminary Experience of Comparative Analysis With 18F-FDG.

Objectives: This study aimed to investigate the physiological distribution characteristics of 68Ga-DOTA-FAPI-04 in the ovary, and assess the feasibility of early diagnosis of primary ovarian disease with 68Ga-DOTA-FAPI-04 PET/CT. Methods: We retrospectively analyzed the data of patients who received 18F-FDG and 68Ga-DOTA-FAPI-04 PET/CT scanning in the Nuclear Medicine Department of our hospital within 3 days from September 2020 to January 2021. We selected the data in which ovaries showed abnormal FDG activity. Patients with abnormal ovarian FDG uptake with focus confirmed by pathological biopsy or clinical follow-up as pathological changes were excluded. The uptake of tracers (18F-FDG and 68Ga-FAPI) was semi-quantitatively analyzed. Results: This study included 14 patients (average age was 38.6). Physiological ovarian uptake was mostly unilateral, and there was no significant difference in SUVmax between the left and right sides (FDGt = 0.272, FAPIt = 0.592). The ovary SUVmax of FDG (4.89 ± 1.84) was statistically significantly higher than that of FAPI (1.53 ± 0.37). The Le/Li ratio on FDG is 3.38 ± 1.81, TBR is 5.81 ± 1.98, while the Le/Li ratio on FAPI is 3.57 ± 1.26, TBR is 0.94 ± 0.19. Conclusion: Our research shows that ovarian functional or pathological changes can be manifested as FDG avid, while 68Ga-DOTA-FAPI-04 has no physiological accumulation in the ovary and is not affected by the menstrual cycle. Therefore, 68Ga-DOTA-FAPI-04 has unique advantages in the diagnosis of ovarian diseases, and can identify them early and accurately.

Elevated 68Ga-FAPI Activity in the Plasmacytoma of the Ribs.

ABSTRACT: 68Ga-labeled quinoline-based fibroblast activation protein inhibitors (68Ga-FAPIs) has been used in the evaluation of a variety of malignancies. We report the case of a patient with rib plasmacytoma, which showed elevated 68Ga-FAPI activity. This case indicated fibroblast activation protein overexpression and some degree of fibrosis in the plasmacytoma lesion. Therefore, 68Ga-FAPI can be a potential tracer in the evaluation of plasmacytoma.

Solitary Adult Rib Langerhans Cell Histiocytosis Evaluated by 18F-FDG PET/CT.

ABSTRACT: Langerhans cell histiocytosis (LCH) is a rare proliferative histiocytic disorder. It mainly occurs in the pediatric population, whereas it is rarely reported in adults. Herein, we reported a case of a patient with isolated rib LCH, which showed elevated 18F-FDG uptake. Our case showed that 18F-FDG PET/CT can be a potential tool in the evaluation of LCH.

A Case of Solitary Laryngotracheal Lymphoma Evaluated by 18F-FDG PET/CT.

ABSTRACT: Solitary non-Hodgkin lymphoma of the trachea is extremely rare. Herein, we reported a case of solitary laryngotracheal lymphoma in a 55-year-old man. He complained of cough, tachypnea, and dyspnea. 18F-FDG PET/CT showed a hypermetabolic lesion in the subglottic larynx and upper cervical trachea. The subsequent histology and immunohistochemistry of the laryngotracheal lesion tissue confirmed the diagnosis of non-Hodgkin lymphoma (mucosa-associated lymphatic tissue lymphoma).

Coverage-driven phase transition of copper silicide monolayer on Si (111).

The characterization and control of atomic substitution process is crucial in fabricating high-quality two-dimensional layered compound materials and tuning their physical properties. With intensity-voltage low energy electron microscopy (IV-LEEM), we found that the concentration of copper in the topmost copper silicide monolayer on Si (111) substrates varies gradually from 1.7 to 1.0 ML while preserving it's unique '5 × 5' incommensurate phase in a transition region as large as 1000 nm. This gradual variation of the copper concentration is due to the incomplete substitution of the Si with Cu, as revealed by atomic-resolved scanning tunneling microscopy with a tip that nicely resolved the '5 × 5' periodicity. Our experiments indicate that besides the widely-accepted phase of Cu2Si with both substitutional and interstitial Cu atoms, another type of precursor copper silicide CuSi3 with only interstitial Cu atoms also plays important roles in the substitutional diffusion and reaction processes during the formation of the topmost copper silicide monolayer. This precursor phase might exist in the growth of other two-dimensional layered materials with potential applications in integrated optoelectronics, spintronics or low dissipative devices.

Dual-Ligand Modified Polymer-Lipid Hybrid Nanoparticles for Docetaxel Targeting Delivery to Her2/neu Overexpressed Human Breast Cancer Cells.

In this study, a dual-ligand polymer-lipid hybrid nanoparticle drug delivery vehicle comprised of an anti-HER2/neu peptide (AHNP) mimic with a modified HIV-1 Tat (mTAT) was established for the targeted treatment of Her2/neu-overexpressing cells. The resultant dual-ligand hybrid nanoparticles (NPs) consisted of a poly(lactide-co-glycolide) core, a near 90% surface coverage of the lipid monolayer, and a 5.7 nm hydrated polyethylene glycol shell. Ligand density optimization study revealed that cellular uptake efficiency of the hybrid NPs could be manipulated by controlling the surface-ligand densities. Furthermore, the cell uptake kinetics and mechanism studies showed that the dual-ligand modifications of hybrid NPs altered the cellular uptake pathway from caveolae-mediated endocytosis (CvME) to the multiple endocytic pathways, which would significantly enhance the NP internalization. Upon the systemic investigation of the cellular uptake behavior of dual-ligand hybrid NPs, docetaxel (DTX), a hydrophobic anticancer drug, was successfully encapsulated into dual-ligand hybrid NPs with high drug loading for Her2/neu-overexpressing SK-BR-3 breast cancer cell treatment. The DTX-loaded dual-ligand hybrid NPs showed a decreased burst release and a more gradual sustained drug release property. Because of the synergistic effect of dual-ligand modification, DTX-loaded dual-ligand hybrid NPs exerted substantially better therapeutic potency against SK-BR-3 cancer cells than other NP formulations and free DTX drugs. These results demonstrate that the dual-ligand hybrid NPs could be a promising vehicle for targeted drug delivery to treat breast cancer.

PEGylated poly(amine-co-ester) micelles as biodegradable non-viral gene vectors with enhanced stability, reduced toxicity and higher in vivo transfection efficacy.

Nanosized micelles based on cationic, amphiphilic poly(ethylene glycol)-poly(ω-pentadecalactone-co-N-methyldiethyleneamine-co-sebacate) (PEG-PPMS) block copolymers have been successfully developed to serve as a new type of biodegradable non-viral vectors for DNA delivery. PEG-PPMS copolymers with various compositions were synthesized in one step via lipase-catalyzed copolymerization of ω-pentadecalactone (PDL), N-methyldiethanolamine (MDEA) and diethyl sebacate (DES) with poly(ethylene glycol) methyl ether (MeO-PEG-OH). The effects of PEG molecular weight, PEG and PDL contents on the biological properties (including the gene transfection efficiency) of the copolymer micelles were investigated. The LucDNA-loaded micelles formed from the copolymers with 30-50 wt% PEG showed high stability in serum-containing aqueous medium, which is in sharp contrast to rapid aggregation of LucDNA/PPMS polyplex particles. The conjugation of PEG to PPMS chains significantly reduces the cytotoxicity and hemolysis activity of the PEG-PPMS micelles. Compared to PEG-free PPMS, the micelles of PEG-PPMS copolymers with optimal compositions (e.g., 42%PEG5K-PPMS-10%PDL and 42%PEG5K-PPMS-20%PDL) exhibited enhanced capability to condense and protect DNA. Although the optimized micelles showed comparable or slightly lower gene transfection efficacy than the reference PPMS in vitro, the efficiency of LucDNA/42%PEG5K-PPMS-20%PDL micelles in transfecting tumor cells in mice was twice as high as that of LucDNA/PPMS polyplex particles due to their strong DNA condensation ability and excellent stability under physiological conditions. The PEG-PPMS micelle system with improved properties is a family of potentially promising non-viral vectors for in vivo delivery of therapeutic genes to treat tumors.

Thioredoxin-1 phosphorylated at T100 is needed for its anti-apoptotic activity in HepG2 cancer cells.

AIMS: Thioredoxin-1 (Trx) is an important protein involved in the regulation of apoptosis and in enhancing drug resistance in cancer cells. Threonine100 (T100) of Trx was reported to be phosphorylated; however, the role of this phosphorylation in regulating activity remains unresolved. We explored whether and how the phosphorylation of Trx is involved in drug resistance in cancer cells. MAIN METHODS: The levels of phosphorylated Trx were detected by sandwich ELISA. Cell viability was investigated using Alamar Blue assay, and apoptosis was evaluated with Hoechst33258 staining. Western blotting was used to examine the changes in the expression levels of Trx, NF-kappaB p65 subunit, ASK-1 and 6His tag. Additionally, we took advantage of phorbol-12-myristate-13-acetate (PMA)to activate protein kinase C (PKC) and staurosporine to inhibit PKC. KEY FINDINGS: Trx mutated at T100 causes lower survival rate induced by H(2)O(2), and higher apoptosis rate induced by cis-platinum and adriamycin in HepG2 cells. T100 of Trx can be phosphorylated through the PKC-dependent pathway. Furthermore, the resistance of anticancer drugs can be decreased when the phosphorylation of T100 in Trx was blocked by staurosporine. Though the Trx-ASK1 complex is not affected, the phosphorylation contributes to the nuclear location of Trx, and then up-regulates the activity of NF-kappaB. SIGNIFICANCE: It was firstly found that the phosphorylation of Trx at T100 plays an important role in its cytoprotective activity in cancer cells. Thus, besides blocking the active site of Trx, inhibiting the phosphorylation of Trx at T100 may be a new potential cancer therapy target.