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Currently, the 5-year survival rate for patients with advanced hepatocellular carcinoma (HCC) is very low. Therefore, there is an urgent need to find new strategies for the treatment of HCC. TMTP1 (NVVRQ) is a tumor-homing peptide that has been shown to target a range of highly metastatic tumor cells. In this study, a novel radiotherapeutic probe, [

Immune checkpoint blockers (ICBs) targeting programmed death receptor 1 (PD-1) ligand 1 (PD-L1) for immunotherapy have radically reformed oncology. It is of great significance to enhance the response rate of ICB in cancer patients. Here, a radioiodinated anti-PD-L1 antibody (

Although KRAS has been an important target for many cancers, direct inhibition of oncogenic RAS remains challenging. Until recently, covalent KRAS G12C-specific inhibitors have been developed and progressed to the clinics. Nevertheless, not all patients benefit from these covalent inhibitors. At present, identification of candidates for this treatment requires tissue biopsies and gene sequencing, which are invasive, time-consuming, and could be of insufficient quality and limited predictive value owing to tumor heterogeneity. The use of noninvasive molecular imaging techniques such as PET and SPECT for spying KRAS G12C mutation in tumors provide a promising strategy for circumventing these hurdles. In the present study, based on the covalent G12C-specific inhibitor ARS-1620, we sought to develop radiolabeled small molecules for direct imaging of the KRAS mutation status in tumors. [131I]I-ARS-1620 and [18F]F-ARS-1620 were successfully prepared with high radiochemical yield, radiochemical purity, and molar activity. In vitro and in vivo studies have demonstrated the affinity, specificity, and capacity of [131I]I-ARS-1620 for direct imaging of the oncogenic KRAS G12C mutant. This initial attempt allows us to directly screen the KRAS G12C mutant for the first time in vivo.

Purpose: Tumor Necrosis Factor Receptor 1 (TNFR1) and integrin αvβ3 receptor are overexpressed in breast cancer. We hypothesized that a peptide ligand recognizing both receptors in a single receptor-binding probe would be advantageous. Here, we developed a novel 18F-labeled fusion peptide probe [18F]-NOTA-Gly3- E(2PEG4-RGD-WH701) targeting dual receptors (TNFR1 and αvβ3) and evaluated the diagnostic efficacy of this radioactive probe in both MDA-MB-231 and MCF-7 xenograft models in mice. Methods: The NOTA-conjugated RGD-WH701 analog was radiolabeled with 18F using NOTA-AlF chelation method. We used two PEG4 molecules and Glutamic acid (Glu) to covalently link c(RGDyK) with WH701. Gly3 was also added to further improve the water solubility and pharmacokinetic properties of the probe. The expression of TNFR1 and Integrin αvβ3 in MCF-7 and MDA-MB-231 cells was detected by western blot analysis and immunofluorescence staining. The tumor-targeting characteristics of [18F]-NOTA-Gly3-E(2PEG4-RGDWH701) were assessed in nude mice bearing MDA-MB-231 and MCF-7 xenografts. Results: HPLC analysis of the product NOTA-G3-E (2P4-RGD-WH701) revealed a purity >95%. The yield after attenuation correction was approximately 33.5%±2.8% (n=5), and the radiochemical purity was above 95%. The MDA-MB-231 tumor uptake of [18]-NOTA-Gly3-E(2PEG4-RGD-WH701) was 1.14±0.14%ID/g, as measured by PET at 40min postinjection (p.i.). In comparison, the tumor uptake of [18F]-NOTA-RGD and [18F]- NOTA-WH701 in MDA-MB-231 xenografts was 0.96±0.13%ID/g and 0.93±0.28%ID/g, respectively. The MCF-7 tumor uptake of [18F]-NOTA-Gly3-E(2PEG4-RGD-WH701) was 1.22±0.11%ID/g, as measured by PET at 40min postinjection (p.i.). In comparison, the tumor uptake of [18F]-NOTA-RGD and [18F]-NOTA-WH701 in MCF-7 xenografts was 0.99±0.18%ID/g and 0.57±0.08%ID/g, respectively. Conclusion: [18F]AlF-NOTA-Gly3-E(2PEG4-RGD-WH701) was successfully synthesized and labeled with 18F. The results from the microPET/CT and biodistribution studies of [18F]AlF-NOTA-Gly3-E(2PEG4-RGDWH701) showed that the tracer could specifically target TNFR1 and integrin αvβ3 receptors.

To explore the expression and clinical significance of factors associated with multiple myeloma (MM) and identify new diagnostic markers.Two gene expression array data sets (GSE6477 and GSE5900) were downloaded and differentially expressed genes (DEGs) in bone marrow from patients with MM and healthy donors analyzed. Kyoto Encyclopedia of Genes and Genomes pathway enrichment and Gene Ontology annotation of DEGs was conducted and a protein-protein interaction network generated. Plasma and bone marrow samples from patients with MM were analyzed for cytokine expression by ELISA and correlations between cytokine levels and clinical indicators evaluated.Of 908 DEGs, 416 were up-regulated and 492 down-regulated. Further, 161 proteins pairs and 21 nodes were detected, and eight hub genes (CXCL2, CXCL8, CXCL12, ELANE, LCN2, CX3CL1, CCL13, and CCL27) screened out. Expression levels of CXCL8, CXCL2, CXCL12, LCN2, and CCL13 were low in CD138+ plasma cells, and expression levels of the eight cytokines differed significantly in peripheral blood plasma from patients with MM and healthy controls. ROC curve analysis determined optimal diagnostic thresholds determined for: CCL27 (189 ng/mL), CXCL2 (313 ng/L), CX3CL1 (132 ng/L), CCL13 (235 pg/mL), CXCL8 (884 ng/L), ELANE (50 µg/L), LCN2 (8 µg/L), and CXCL12 (2525 pg/mL).CX3CL1, CCL13, CXCL8, and CXCL12 levels were positively correlated with those of hemoglobin and β2 microglobulin (β2-MG); CCL27 and CXCL2 with β2-MG; and CCL13 and ELANE with white blood cell count and age, respectively. CCL27, CXCL2, and β2-MG levels were associated with MM incidence.

Overexpression of estrogen receptors (ERs) is one of the important characteristics of most breast cancers. We aim to develop a new type of ER-specific radioiodine-labeled estrogen derivative ([

Multiple myeloma is a clonal disorder of malignant plasma cells that comprises approximately 10% of hematologic malignancies. The aim of this study was to investigate the efficacy and toxicity of carfilzomib- or bortezomib-based regimens for treatment of transplant-ineligible patients with newly diagnosed multiple myeloma by performing a meta-analysis of randomized controlled trials (RCTs).Data mining was conducted in March 2022 across PubMed, EMBASE and ClinicalTrials.gov. All published RCTs which assessed efficacy and toxicity of carfilzomib-based regimens treatment for transplant-ineligible patients with newly diagnosed multiple myeloma when compared with a bortezomib-based regimens were included.Our meta-analysis showed that the overall response rate (ORR) (Odds ratio = 1.33, 95% CI 1.05-1.69, P = .02) was significantly higher in the carfilzomib-based regimens group than in the bortezomib-based regimens group. However, the difference in ORR did not translate into improvements in progression-free survival (PFS), overall survival (OS) and complete response rate (CRR). Adverse events of grade 3 or worse that occurred with a higher incidence in the carfilzomib-based regimens group compared with the bortezomib-based regimens group were dyspnea, hypertension, acute kidney injury, and heart failure.The carfilzomib-based regimens did not improve PFS, OS and CRR compared with the bortezomib-based regimens in transplant-ineligible patients with newly diagnosed multiple myeloma, and they showed higher toxicity.

Tumor necrosis factor receptor 1 (TNFR1) is overexpressed in several varieties of carcinoma, including breast cancer. WH701 (Ala-Thr-Ala-Gln-Ser-Ala-Tyr-Gly), which was identified by phage display, can specifically bind to TNFR1. In this study, we labeled WH701 with

The aims of this study were to evaluate the diagnostic value of adenosine thallium-201 myocardial perfusion imaging and to compare it with exercise stress thallium-201 myocardial perfusion imaging for detecting coronary artery disease (CAD) at an early stage. Forty-one patients suspected with CAD were randomly divided into two groups. In Group 1 (n=21) adenosine stress was undertaken; the exercise stress myocardial perfusion imaging was performed in Group 2 (n=20). Coronary angiography (CAG) was performed in each patient within 2 weeks before or after single photon emission computed tomography (SPECT). Adenosine stress group vs. exercise stress group, the sensitivity was 92.86% vs. 100.0%, specificity 57.14% vs. 60.0%, positive predictive value 81.25% vs. 71.43%, negative predictive value 80.0% vs. 100.0%, accuracy 80.95% vs. 80.0% respectively. Detection rates of vessels of coronary artery lesions were 66.67% in Group 1 and 72.22% in Group 2 (P> 0.05). The side effects were mild and transient. Our results demonstrated that adenosine stress myocardial perfusion imaging is a safe and reliable diagnostic method for an early stage of CAD. As a comparative sensitivity and accuracy with exercise stress thallium-201 myocardial perfusion imaging, adenosine stress testing may provide a feasible alternative pharmacological stress method in myocardial SPECT for detection of CAD.