Gadolinium-neutron capture therapy (Gd-NCT) employs isotopically enriched Gadolinium (Gd) and thermal neutrons to selectively target cancer cells. This study investigated the targeting efficacy of 157Gd-DOTA-PSMA (Prostate-Specific Membrane Antigen) in prostate cancer and explored its potential applications in Gd-NCT. We developed 157Gd-DOTA-PSMA, a novel theranostic bio-gadolinium agent specifically designed for magnetic resonance imaging (MRI)-guided Gd-NCT. 68 Ga-DOTA-PSMA positron emission tomography-computed tomography (PET/CT) imaging showed peak radiotracer uptake at 2 h post-injection, with a tumor-to-non-tumor (T/NT) ratio of 6.95 ± 0.60. MRI analysis confirmed a stable T1 signal enhancement 2 h post-injection. Time-of-flight inductively coupled plasma mass spectrometry (TOF-ICP-MS) revealed significantly elevated Gd concentrations in 22Rv1 tumor compared to PC-3 tumor and other healthy organs. ICP-MS analysis showed Gd concentrations of 165.69 μg [Gd]/g in 22Rv1 tumors and 35.25 μg [Gd]/g in blood, yielding a tumor-to-blood (T/B) ratio of 4.65 ± 0.54 and a T/NT ratio of 3.65 ± 0.49. Neutron irradiation with 157Gd-DOTA-PSMA reduced cell viability, inhibited colony formation, and induced DNA damage and apoptosis in 22Rv1 cells. In 22Rv1 mice, γ-H2AX levels peaked at 6 h post-irradiation, accompanied by an increase in pro-apoptotic proteins and a decrease in anti-apoptotic proteins over 24 h. In the NCT group following the injection of 157Gd-DOTA-PSMA, there was effective suppression of tumor growth without a loss of body weight, resulting in a 1.7-fold increase in median survival compared to control group. 157Gd-DOTA-PSMA, as a theranostic bio-gadolinium agent designed for targeted Gd-NCT in prostate cancer, represents a novel therapeutic approach and broadens the scope of potential applications of neutron capture therapy.

The aim of this study is to assess the impact of internal conversion (IC) and Auger electrons released during gadolinium neutron capture therapy (157GdNCT) on the amount of DNA damage induced and the relative biological effectiveness (RBE) across varying cellular structures and types. We developed cell models that featured simplified chromosome geometries with diverse shapes and base pair densities, utilizing the Geant4-DNA package. The RBE values of these secondary electrons were determined based on the DNA double-strand breaks (DNA-DSBs) endpoint. The findings revealed that the more the distribution of gadolinium is concentrated in the nucleus, the greater the degree of DNA damage. In the cytoplasm, the influence of secondary electrons on DNA damage were not related to cell shape. However, when the secondary electrons were distributed in the nuclear membrane, the RBE of the secondary electrons was affected by the cell shape. When there is a greater difference in base pair density, more pronounced discrepancies in the yield of DSBs are evident. As the base pair density decreased, the yield of DSBs increased. Furthermore, the yield of DSBs exceeded 8.63 +/- 0.33 DSBs/Gy/Gbp under different influencing factors. The RBE range of IC electrons and Auger electrons released from 157GdNCT based on DNA-DSBs endpoints was found to be between 0.8 and 1.6.

Objective:This study aims to investigate the significance of interim whole-body dynamic 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) Patlak parameters for predicting the prognosis of patients with diffuse large B-cell lymphoma. To estimate the predictive value of the whole-body dynamic 18F-FDG PET/CT Patlak parameter for 2-year progression-free survival (PFS) and 2-year overall survival (OS). Methods:This study reports the findings of 67 patients with diffuse large B-cell lymphoma (DLBCL). These patients underwent interim whole-body dynamic 18F-FDG PET/CT scans from June 2021 to January 2023 at the Department of Nuclear Medicine, First Affiliated Hospital of Anhui Medical University. The predictive values of maximum standard uptake value (SUVmax), maximum of net glucose uptake rate (Kimax) and the predictive model combining Kimax and interim treatment response on the prognosis of patients was analyzed using receiver operating characteristic (ROC) curves. Kaplan-Meier survival curves and log-rank tests were used for survival analysis. Univariate and multivariate analyses were performed to screen for independent prognostic risk factors. Results:After a median follow-up of 18 months, 21 patients (31.3%) experienced disease recurrence or death. The cut-off values for the SUVmax and the Kimax were 6.1 and 0.13 μmol min-1·ml-1, respectively. Ann Arbor stage, IPI, SUVmax, Kimax and interim treatment response were associated with PFS and OS in the univariate analysis. However, only Kimax and interim treatment response were independent influences on PFS and OS in multivariate analysis. Conclusion:Interim whole-body dynamic 18F-FDG PET/CT Patlak imaging has significant prognostic value in patients with DLBCL. Among them, the interim dynamic parameter Kimax showed the best predictive value for prognosis compared with the interim SUVmax and interim treatment response. The predictive model established by Kimax and the interim treatment response allowed for the accurate stratification of the prognostic risk of DLBCL.

Radiotherapies are commonly used to target remaining tumor niches after surgery of solid tumors but are restricted due to therapeutic resistance. Several pathways of radioresistance have been reported in various cancers. This study investigates the pivotal role of Nuclear factor-erythroid 2-related factor 2 (NRF2) in the activation of DNA damage repair in lung cancer cells after x-rays exposure. To explore the NRF2 activation after ionizing irradiations, this study uses a knockdown of NRF2, which shows potential DNA damage after x-rays irradiation in lung cancers. This work further shows that NRF2 knockdown disrupts damaged DNA repair by inhibiting DNA-dependent protein kinase catalytic subunit. At the same time, NRF2 knockdown by shRNA considerably disparate homologous recombination by interfering with Rad51 expression. Further investigation of the associated pathway reveals that NRF2 activation mediates DNA damage response via the mitogen-activated protein kinase (MAPK) pathway as the knockout of NRF2 directly enhances intracellular MAPK phosphorylation. Similarly, both N-acetylcysteineand constitutive knockout of NRF2 disrupt DNA-dependent protein kinase catalytic subunit, while NRF2 knockout failed to upregulate Rad51 expression after irradiation in-vivo. Taken together, these findings advocate NRF2 plays a critical role in the development of radioresistance by upregulating DNA damage response via the MAPK pathway, which can be of great significance.

Gamma-emitting radionuclide 99mTc is globally used for the diagnosis of various pathological conditions owing to its ideal single-photon emission computed tomography (SPECT) characteristics. However, the short half-life of 99mTc (T1/2 = 6 h) makes it difficult to store or transport. Thus, the production of 99mTc is tied to its parent radionuclide 99Mo (T1/2 = 66 h). The major production paths are based on accelerators and research reactors. The reactor process presents the potential for nuclear proliferation owing to its use of highly enriched uranium (HEU). Accelerator-based methods tend to use deuterium–tritium (D–T) neutron sources but are hindered by the high cost of tritium and its challenging operation. In this study, a new 99Mo production design was developed based on a deuterium–deuterium (D–D) gas dynamic trap fusion neutron source (GDT-FNS) and a subcritical blanket system (SBS) assembly with a low-enriched uranium (LEU) solution. GDT-FNS can provide a relatively high-neutron intensity, which is one of the advantages of 99Mo production. We provide a Monte Carlo-based neutronics analysis covering the calculation of the subcritical multiplication factor (ks) of the SBS, optimization design for the reflector, shielding layer, and 99Mo production capacity. Other calculations, including the neutron flux and nuclear heating distributions, are also provided for an overall evaluation of the production system. The results demonstrated that the SBS meets the nuclear critical safety design requirement (ks < 0.97) and maintained a high 99Mo production capacity. The proposed system can generate approximately 157 Ci 99Mo for a stable 24 h operation with a neutron intensity of 1 × 1014 n/s, which can meet 50

Abstract Background Contrast-enhanced ultrasound (CEUS) has been recently used for the assessment of cervical lymph node metastasis (LNM) to guide surgical operation in patients with papillary thyroid carcinoma (PTC). However, the specificity and sensitivity of CEUS reported from previous studies are not consistent. The objective of this study was to evaluate the diagnostic value of CEUS for the metastasis of cervical lymph nodes in PTC patients based on data from one regional central hospital. Methods The diagnostic value of CEUS in preoperative LNM of PTC patients was concluded by comparing the results of CEUS on lymph node status with postoperative pathology examination. In addition, this study conducted hierarchical analysis of PTC patients to explore whether tumor size, different lymph node regions, and Hashimoto’s thyroiditis influence the assessment of CEUS. Results This research study ultimately enrolled 965 PTC patients, including 266 males and 699 females with a mean age of 42.27 ± 11.34 years. A total of 527 patients were considered clinical-node negative, and 438 were clinical-node positive before surgery. The specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CEUS in the assessment of LNM in PTC patients were 56.00%, 71.00%, 57.06%, 69.76% and 62.59%, respectively. For central and lateral lymph nodes, the accuracy of CEUS in PTC patients was 49.43% and 54.30%, respectively. In addition, it was shown that the accuracy of CEUS in PTC patients with Hashimoto’s thyroiditis (HT) slightly decreased to 58.44%, and the accuracy of CEUS in PTC patients with non-HT in turn increased to 64.17%. The accuracy of CEUS in non-papillary thyroid microcarcinoma (PTMC) and PTMC patients was 65.68% and 61.24%, respectively. The accuracy of CEUS in predicting central LNM was significantly different between PTC patients with or without HT (P < 0.001) in this study but not for lateral lymph nodes (P = 0.114). Conclusion The accuracy of CEUS in the assessment of LNM in PTC is not consistently satisfactory, especially for central lymph nodes, small tumor diameters, or patients with HT. More diagnostic technologies for abnormal lymph nodes should be considered in PTC patients.

Connexin26 (Cx26) plays an important role in ionizing radiation-induced damage, and CC chemokine ligand 27 (CCL27) regulates the skin immune response. However, the relationship between Cx26 and CCL27 in radiation-induced skin damage is unclear. After X-ray irradiation, clonogenic survival and micronucleus formation were assessed in immortalized human keratinocytes (HaCaT). Proteins in the mitogen activated protein kinase (MAPK) signaling pathway and CCL27-related proteins were detected by immunoblotting. HaCaTCx26-/- cells were constructed to verify the effects of Cx26 on CCL27 secretion. A mouse model was established to examine the expression of CCL27 and skin inflammation in vivo. The degree of skin injury induced by 6 MV of X rays was closely related to CCL27. The phosphorylation of ERK, p38 and NF-κB was significantly increased in irradiated cells. The secretion of CCL27 was significantly decreased in HaCaT wild-type cells relative to HaCaTCx26-/- cells. Whereas cell survival fractions decreased, and the micronuclei formation rate increased as a function of increasing X-ray dose in HaCaT cells, the opposite trend occurred in HaCaTCx26-/- cells. Our findings show that Cx26 likely plays a role in the activation of the MAPK and NF-κB/COX-2 signaling pathways and regulates the secretion of CCL27 in keratinocytes after X-ray radiation-induced skin damage.

Despite the recent progress of medical technology in the diagnosis and treatment of tumors, pancreatic carcinoma remains one of the most malignant tumors, with extremely poor prognosis partly due to the difficulty in early and accurate imaging evaluation. This paper focuses on the research progress of magnetic resonance imaging, nuclear medicine molecular imaging and radiomics in the diagnosis of pancreatic carcinoma. We also briefly described the achievements of our team in this field, to facilitate future research and explore new technologies to optimize diagnosis of pancreatic carcinoma.

1 Department of Ultrasound, First Affiliated Hospital of Chongqing Medical University, Chongqing, China, 2 Department of Orthopaedics, First Affiliated Hospital of Chongqing Medical University, Chongqing, China, 3 Department of Radiology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China, 4 Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Chongqing Medical University, Chongqing, China

NLRC5 is an important regulator in antigen presentation and inflammation, and its dysregulation promotes tumor progression. In melanoma, the impact of NLRC5 expression on molecular phenotype, clinical characteristics, and tumor features is largely unknown. In the present study, public datasets from the Cancer Cell Line Encyclopedia (CCLE), Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and cBioPortal were used to address these issues. We identify that NLRC5 is expressed in both immune cells and melanoma cells in melanoma samples and its expression is regulated by SPI1 and DNA methylation. NLRC5 expression is closely associated with Breslow thickness, Clark level, recurrence, pathologic T stage, and ulceration status in melanoma. Truncating/splice mutations rather than missense mutations in NLRC5 could compromise the expression of downstream genes. Low expression of NLRC5 is associated with poor prognosis, low activity of immune-related signatures, low infiltrating level of immune cells, and low cytotoxic score in melanoma. Additionally, NLRC5 expression correlates with immunotherapy efficacy in melanoma. In summary, these findings suggest that NLRC5 acts as a tumor suppressor in melanoma via modulating the tumor immune microenvironment. Targeting the NLRC5 related pathway might improve efficacy of immunotherapy for melanoma patients.

Lung adenocarcinoma is one of the most frequent tumor subtypes, involving changes in a variety of oncogenes and tumor suppressor genes. Hydroxysteroid 17-Beta Dehydrogenase 6 (HSD17B6) could synthetize dihydrotestosterone, abnormal levels of which are associated with progression of multiple tumors. Previously, we showed that HSD17B6 inhibits malignant progression of hepatocellular carcinoma. However, the mechanisms underlying inhibiting tumor development by HSD17B6 are not clear. Moreover, its role in lung adenocarcinoma (LUAD) is yet unknown. Here, we investigated its expression profile and biological functions in LUAD. Analysis of data from the LUAD datasets of TCGA, CPTAC, Oncomine, and GEO revealed that HSD17B6 mRNA and protein expression was frequently lower in LUAD than in non-neoplastic lung tissues, and its low expression correlated significantly with advanced tumor stage, large tumor size, poor tumor differentiation, high tumor grade, smoking, and poor prognosis in LUAD. In addition, its expression was negatively regulated by miR-31-5p in LUAD. HSD17B6 suppressed LUAD cell proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and radioresistance. Furthermore, HSD17B6 overexpression in LUAD cell lines enhanced PTEN expression and inhibited AKT phosphorylation, inactivating downstream oncogenes like GSK3β, β-catenin, and Cyclin-D independent of dihydrotestosterone, revealing an underlying antitumor mechanism of HSD17B6 in LUAD. Our findings indicate that HSD17B6 may function as a tumor suppressor in LUAD and could be a promising prognostic indicator for LUAD patients, especially for those receiving radiotherapy.