The earliest optimal timing for total-body 68Ga-fibroblast activation protein inhibitor-04 PET scans: an evidence-based single-centre study.

OBJECTIVES: To investigate the earliest optimal timing for positron emission tomography (PET) scans after 68Ga-fibroblast activation protein inhibitor-04 ([68Ga]Ga-FAPI-04) injection. METHODS: This prospective study enrolled patients who underwent 60-min dynamic 68Ga-FAPI-04 total-body PET/CT scans; the images were reconstructed at 10-min intervals (G0-10, G10-20, G20-30, G30-40, G40-50, and G50-60), and the [68Ga]Ga-FAPI-04 uptake patterns were evaluated. The standardised uptake value (SUV), liver signal-to-noise ratio (SNR), and lesion-to-background ratios (LBRs) for different time windows were calculated to evaluate image quality and lesion detectability. The period from 30 to 40 min was then split into overlapping 5-min intervals starting 1 min apart for further evaluation. G50-60 was considered the reference. RESULTS: A total of 30 patients with suspected malignant tumours were analysed. In the images reconstructed over 10-min intervals, longer acquisition times were associated with lower background uptake and better image quality. Some lesions could not be detected until G30-40. The lesion detection rate, uptake, and LBRs did not differ significantly among G30-40, G40-50, and G50-60 (all p > 0.05). The SUVmean and LBRs of primary tumours in the reconstructed images did not differ significantly among the 5-min intervals between 30 and 40 min; for metastatic and benign lesions, G34-39 and G35-40 showed significantly better SUVmean and LBR values than the other images. The G34-39 and G50-60 scans showed no significant differences in uptake, LBRs, or detection rates (all p > 0.05). CONCLUSION: The earliest optimal time to start acquisition was 34 min after injection of half-dose [68Ga]Ga-FAPI-04. CLINICAL RELEVANCE STATEMENT: This study evaluated 68Ga-fibroblast activation protein inhibitor-04 ([68Ga]Ga-FAPI-04) uptake patterns by comparing the image quality and lesion detection rate with 60-min dynamic [68Ga]Ga-FAPI-04 total-body PET/CT scans and identified the earliest optimal scan time after [68Ga]Ga-FAPI-04 injection. KEY POINTS: • A prospective single-centre study showed that the earliest optimal time point to start acquisition was 34 min after injection of half-dose [68Ga-fibroblast activation protein inhibitor-04 (68Ga]Ga-FAPI-04). • There were statistically significant differences in standardised uptake value, lesion-to-background ratios, and lesion detectability between scans before and after 34 min from the injection of [68Ga]Ga-FAPI-04, but these values did not change further from 34 to 60 min after injection. • With a reasonable acquisition time, the image quality could still meet diagnostic requirements.

Recovery of phosphate as struvite from low-temperature combustion sewage sludge ash (LTCA) by cation exchange.

As a phosphorus-rich material, low-temperature combustion sewage sludge ash (LTCA) contains over 9 wt% content of phosphorus (P) and a large proportion of impurities, especially the content of Fe arrives at 14.59 wt%. To fully utilize LTCA as a fertilizer, this study investigated a procedure for P recovery from LTCA via struvite crystallization with fewer impurities. The adsorption characteristics of P and Fe by cation exchange resin (CER) were explored by simulating using the macroscopic parametric equation Thomas model. Optimum purification conditions for P-rich leachate by cation exchange column method were determined. Results showed that approximately 97.21 wt% of P was extracted from LTCA at HCl concentration of 0.8 M and liquid/solid ratio of 20.0 ml/g. More than 90 wt% of impurities could be detached by making P-rich leachate flow through cation exchange bed filled by CER at 300 ml/h. The macroscopic parametric equation Thomas model could clearly describe the adsorption characteristics of Fe in P-rich leachate by CER. Theoretical basis for purification of high concentration Fe in P-rich leachate by CER was provided. Approximately 84.04 wt% of total P in LTCA was recovered as struvite crystal which had low concentrations of heavy metals (5.96 mg/kg for Cr, 45.21 mg/kg for Cu, 29.67 mg/kg for Ni, 2.24 mg/kg for Pb, and 290.6 mg/kg for Zn) and could be eco-friendly for agricultural application. X-ray diffraction and SEM-EDS analysis validated the formation of struvite.

Improved utilization of phosphorous from sewage sludge (as Fertilizer) after treatment by Low-Temperature combustion.

The utilization of phosphorus from sewage sludge is an important method used to solve the shortage of phosphorus resources in the world. However, high levels of toxic compounds and low phosphorus bioavailability in sewage sludge are the main factors limiting its direct agricultural use. This paper proposes a low-temperature combustion method that can enrich the phosphorus in sludge ash. Low temperature-treated sewage sludge ash (LTSA) at different oxygen concentrations (20%, 60%, 100%) were obtained through a specific experimental device. Then, the species and leaching characteristics of phosphorus in LTSAs were analyzed and compared with pyrolysis sewage sludge char (PSSC) and incinerated sewage sludge ash (ISSA). Results show that low-temperature combustion of sludge increased the total phosphorus content in the bottom ash by 45.6%, and the bioavailable phosphorus content increased 2.9 times. Further, by increasing the concentration of oxygen while carrying out low-temperature combustion of sludge, part of the non-apatite inorganic P was converted to apatite P (AP), resulting in a 46.3% increase in AP in the sludge. Low-temperature combustion can also convert heavy metals (Cd, Cr, Cu, Pb, and Zn) in the sludge from an easily leachable form (acid extractable fraction and reducible fraction) to a stable form (reducible fraction) and decrease the leaching of heavy metals. Leaching of Cr and Cu decreased by 97.56% and 98.52%, respectively.

Silencing Artemis Enhances Colorectal Cancer Cell Sensitivity to DNA-Damaging Agents.

Artemis is a key protein of NHEJ (nonhomologous end joining), which is the major pathway for the repair of IR-induced DSBs in mammalian cells. However, the expression of Artemis in tumors and the influence of silencing Artemis on tumor sensitivity to radiation have not been investigated fully. In this study, we investigated how the expression levels of Artemis may affect the treatment outcome of radiotherapy and chemotherapy in colorectal cancer cells. First, we found that the expression of Artemis is strong in some human rectal cancer samples, being higher than in adjacent normal tissues using immunohistochemical staining. We then knocked down Artemis gene in a human colorectal cancer cell line (RKO) using lentivirus-mediated siRNAs. Compared to the control RKO cells, the Artemis knockdown cells showed significantly increased sensitivity to bleomycin, etoposide, camptothecin, and IR. Induced by DNA-damaging agents, delayed DNA repair kinetics was found by the γ-H2AX foci assay, and a significantly increased cell apoptosis occurred in the Artemis knockdown RKO cells through apoptosis detection methods and Western blot. We also found that the p53/p21 signaling pathway may be involved in the apoptosis process. Taken together, our study indicates that manipulating Artemis can enhance colorectal cancer cell sensitivity to DNA-damaging agents. Therefore, Artemis can serve as a therapeutic target in rectal cancer therapy.

[Stable isotope labeling and parallel reaction monitoring-based proteomic quantification for biomarker screening and validation of hepatocellular carcinoma].

Liver cancer is the fifth most common cancer with extremely low five year survival rate. Early diagnosis is of great importance for cancer therapy. In this work, stable isotope labeling-based relative quantitative proteomics and parallel reaction monitoring-based target proteomics were combined for cancer biomarker screening and validation. By using this strategy, 70 significantly changed proteins in hepatocellular carcinoma tissues were obtained, among which seven proteins were further validated. The validated proteins contain the clinically used hepatocellular carcinoma (HCC) biomarker alpha-fetoprotein (AFP) and the reported biomarker candidates Heat shock protein HSP 90-beta (HSP90), fatty acid-binding protein, epidermal (FABP5) and alcohol dehydrogenase 4 (ADH4), which demonstrated the robustness of the strategy. The proteins identified in this work could be benefit for further HCC biomarker screening and clinical validation. Moreover, this strategy could be further applied to other cancer types.

Nimotuzumab abrogates acquired radioresistance of KYSE-150R esophageal cancer cells by inhibiting EGFR signaling and cellular DNA repair.

BACKGROUND: Acquired radioresistance of cancer is common after repeated irradiation and often leads to treatment failure. This study aimed to examine the effects of nimotuzumab on acquired radioresistance in human esophageal carcinoma cells and to investigate its underlying mechanisms. METHODS: The radioresistant human esophageal carcinoma cell line KYSE-150R was generated by using fractionated irradiation. KYSE-150R cells were pretreated with or without nimotuzumab before ionizing radiation. Cell growth and colony formation were measured to quantitate the effects of radiation. The γ-H2AX foci assay was employed to determine cellular DNA-repairing capacity. The phosphorylation of key molecules involved in the epidermal growth factor receptor (EGFR) signaling pathway and cellular DNA repair was measured by Western blot analysis. RESULTS: Nimotuzumab enhanced radiation-induced inhibition on cell growth and clonogenic survival in KYSE-150R cells. The average number of γ-H2AX foci increased in the irradiated cells treated with nimotuzumab. Nimotuzumab inhibited phosphorylation of the EGFR and its downstream molecules AKT and ERK. Phosphorylation of the DNA repair-related proteins DNA-PKcs, ATM, and RAD51 was also inhibited by nimotuzumab. CONCLUSIONS: These results indicate that nimotuzumab can inhibit key cancer survival mechanisms, the EGFR signaling pathway, and DNA repair and thereby reverse acquired radioresistance in KYSE-150R cell line.