OBJECTIVES: We analyzed the effects of anti-hedgehog signaling on the 18F-FDG uptake of pancreatic cancer xenografts (PCXs) using a clinically implemented positron emission tomography (PET)-computer tomography (CT) scanner with high-resolution reconstruction. METHODS: PCXs from two pancreatic cancer cell lines were developed subcutaneously in nude mice and injected intraperitoneally with a low dose of cyclopamine for 1 week. 18F-FDG PET-CT was performed using a new-generation clinical PET-CT scanner with minor modifications of the scanning protocol to adapt for small-animal imaging. The data set was reconstructed and quantified using a three-dimensional workstation. RESULTS: MiaPaCa-2 cells, which respond to cyclopamine, showed decreased 18F-FDG uptake without a change in tumor size. For hip tumors, the maximum standardized uptake value (SUVmax) was reduced by -24.5 ± 9.2%, the average SUV (SUVavg) by -33.5 ± 7.0%, and the minimum SUV (SUVmin) by -54.4 ± 11.5% (P < .05). For shoulder tumors, SUVmax was reduced by -14.7 ± 7.5%, SUVavg by -12.6 ± 6.3, and SUVmin by -30.3 ± 16.7% (P < .05). Capan-1 cells, which do not respond to cyclopamine, did not show significant SUV changes. CONCLUSIONS: The new generations of clinically implemented PET-CT scanners with high-resolution reconstruction detect a minimal response of PCX to low-dose short-term cyclopamine therapy without changes in tumor size and offer potential for preclinical translational imaging.
As many patients ultimately relapse after chimeric antigen receptor (CAR) T-cell therapy, identification of alternative targets is currently being evaluated. Substantial research efforts are underway to develop new targets. The transferrin receptor (TfR) is prevalently expressed on rapidly proliferating tumor cells and holds the potential to be the alternative target. In order to investigate the efficacy and challenges of TfR-targeting on the CAR-based therapy strategy, we generated a TfR-specific CAR and established the TfR-CAR-modified T cells. To take the advantage of TfR being widely shared by multiple tumors, TfR-CAR T cells were assessed against several TfR+ hematological malignant cell lines. Data showed that TfR-CAR T cells were powerfully potent in killing all these types of cells in vitro and in killing T-ALL cells in vivo. These findings suggest that TfR could be a universal target to broaden and improve the therapeutic efficacy of CAR T cells and warrant further efforts to use these cells as an alternative CAR T cell product for the therapy of hematological malignancies.
The secreted form of 78-kDa glucose-regulated protein (sGRP78) has been widely reported for its property in aiding resolution of inflammatory. However, little is known on its potential in the treatment of colitis. To investigate the expression pattern and functional outcome of GRP78 in ulcerative colitis, its expression was measured in human and murine colitis samples. It was found that GRP78 was spontaneously secreted to a high level in gut, which is a physiological site of immune tolerance. During the active phase of DSS-induced colitis, the sGRP78 level was significantly reduced but rebounded quickly during resolving phase, making it a potential candidate for the treatment of colitis. In the following experiments, the administration of sGRP78 was proved to decrease susceptibility to experimental colitis, as indicated by an overall improvement of intestinal symptoms, restoration of TJ integrity, decreased infiltration of immune cells and impaired production of inflammatory cytokines. And specific cleavage of endogenous sGRP78 could aggravate DSS colitis. Adoptive transfer of sGRP78-conditioned BMDMs reduced inflammation in the gut. We linked sGRP78 treatment with altered macrophage biology and skewed macrophage polarization by inhibiting the TLR4-dependent MAP-kinases and NF-κB pathways. Based on these studies, as a naturally occurring immunomodulatory molecule, sGRP78 might be an attractive novel therapeutic agent for acute intestinal inflammation.
Abstract Primary leiomyosarcoma of bone (PLB) is an ultrarare tumor, characterized by its aggressive clinical behavior, high heterogeneity, and dismal prognosis. Here, we present the 68 Ga-FAPI-04 and 18 F-FDG PET/CT findings in a case of PLB affecting the left femur. FAPI PET/CT showed more bone lesions and higher uptake in the multiple metastatic lesions compared with FDG PET/CT. More interestingly, FAPI PET/CT could clearly detect the tumor embolus on the left common femoral artery, which was negative on FDG. This case suggests that FAPI PET/CT is a promising method for the primary diagnosis and staging of PLB.
Inflammation plays a significant role in many physiological and pathological processes. Molecular imaging could provide functional as well as anatomical information for visualizing various inflammatory diseases. Advancements in imaging tracers for inflammation would improve the accuracy of diagnosis and monitoring, thus facilitating patient care. The positron emission tomography (PET) imaging tracer, 68Ga-labeled antagonist peptide Trp-Arg-Trp-Trp-Trp-Trp (WRWWWW, WRW4), targets formyl peptide receptor 2 (FPR2), which is in turn widely distributed in a variety of tissues and is associated with many inflammatory diseases. In the current study, we aimed to investigate the potential of 68Ga-WRW4 for detecting and monitoring inflammatory lesions in mice. We established an inflammation mouse model by the intramuscular injection of turpentine oil into the left thigh. WRW4 was labeled with 68Ga with an overall radiochemical yield >90% and radiochemical purity >99%. 68Ga-WRW4 uptake in inflamed muscle peaked on day 2 (1.14 ± 0.01 percentage of the injected dose per gram of tissue (%ID/g)) and the uptake ratio of inflammatory/normal muscle also reached a maximum (12.36 ± 2.35). Strong PET signals were detected in the left thigh at 60 min after the injection of 68Ga-WRW4 in experimental mice, but weak or no signals were detected in mice in the blocking and control groups. 68Ga-WRW4 uptake was in agreement with the dynamics of immune cell infiltration during the inflammatory reaction. These results suggest that 68Ga-WRW4 is a promising PET tracer suitable for the noninvasive detection of FPR2 expression and for monitoring inflammatory activity in inflammation-bearing mice.
Objective To explore the imaging identification value of CT and MRI in chronic obstructive pulmonary disease. Methods 71 patients with chronic obstructive pulmonary disease admitted into the hospital from April 2013 to December 2014 were selected as the observation group,and 71 cases of healthy physical examination as the control group.MRI and CT were respectively performed in two groups.CT measurement,pulmonary function indexes and results of COPPD type for two kinds of methods were compared between the two groups. Results The RV,TLC,left lung, right lung and whole-lung E/L in the observation group were higher than those in the control group,while FEV1 and FEV1/VCMAX were lower than those in the control group and the comparison was statistically significant(P0.05).There were 69 cases of confirmed diagnosis with CT examination and the sensitivity was 97.2% which was significantly higher than that of MRI and the comparison was statistically significant(P0.05). Conclusion CT for diagnosis of COPD can better display pathological changes of lung tissue and structure in patients,which is conducive to the early diagnosis with higher sensitivity.Combined with MRI,it can be used to identify patients with ventilation,perfusion and respiratory mechanics information,which can provide a powerful reference for clinical treatment.
A 67-year-old man, with decades of smoking history, complained of chronic low back pain for over 2 months. Magnetic resonance imaging showed a lytic lesion in the L2 vertebral body where bone metastasis was suspected. Fluorine 18 (18F)-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images revealed a tiny pulmonary nodule measuring 9 mm in the largest diameter, with no FDG uptake (Fig. 1B and C). The maximum intensity projection image showed FDG-avid bone lesion (SUVmax, 6.9) in the L2 vertebral body and mild-to-moderate FDG accumulation in the mediastinal and bilateral hilar lymph nodes (Fig. 1A). Gallium 68(68Ga)-labeled fibroblast activation protein (FAP) inhibitors (FAPI) PET/CT was performed the next day to determine if the nodule was the primary tumor. The imaging showed focal FAPI uptake (SUVmax, 4.8) in the solitary pulmonary nodule and intense uptake (SUVmax, 31.3) in the bone lesion (Fig. 2A–C) without abnormal uptake of any other site. FDG-positive lymph nodes were not visualized and were considered to be reactive lymphadenitis. The patient received CT-guided percutaneous biopsy of the L2 lesion. The pathology and immunohistochemistry revealed it as metastatic adenocarcinoma (TTF-1: positive; Napsin A: positive; Ki-67:10%; Fig. 3A–D). The combination of TTF-1 and Napsin A is the reliable marker for the diagnosis of lung adenocarcinoma (1–3). Therefore, the pulmonary nodule was diagnosed as the primary lung adenocarcinoma combined with the histologic findings and 68Ga-FAPI PET imaging. Then, pyramidectomy and artificial vertebral body implantation were performed because the patient refused a pneumonectomy. Then, stereotactic body radiation therapy was performed for the pulmonary nodule twice without progression in 6 months.
The author reports a case of small cell carcinoma of the cervix. The patient had a 7-day history of headache and a hard mass in the parietal region of the cranium on the right side as the first manifestation. Cranial CT scan showed a high-density nodule on the right parietal lobe, with a surrounding low-density edema and adjacent skull bone destruction; thus, intracranial tumor was considered. MRI brain scan showed a slightly longer T1 and T2 signal nodule, with edema in the right parietal lobe. The lesion was significantly enhanced after the application of contrast. The 18F-FDG PET/CT whole-body imaging showed a solid mass of cervix and slightly large bilateral pelvic lymph nodes and presented multiple bone destruction with high FDG uptake. The histopathological examination revealed small cell carcinoma of the cervix. Small cell carcinoma of the cervix has extremely low incidence, its clinical manifestation lacks specificity, and it is not easily detected at its early stage. Small cell carcinoma of the cervix is an aggressive tumor and commonly have early metastasis through lymph node and blood circulation, with a poor prognosis. The sensitivity of 18F-FDG PET/CT in detecting primary lesions and metastases, including lymph node, bone, and other occult lesions, is high. Thus, this method is valuable in the clinical management of the small cell carcinoma of the cervix.
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