The combined therapeutic effects of \u3csup\u3e131\u3c/sup\u3eiodine-labeled multifunctional copper sulfide-loaded microspheres in treating breast cancer

Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis. In this study, we prepared multifunctional microspheres loading 131I-labeled hollow copper sulfide nanoparticles and paclitaxel (131I-HCuSNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats. 18F-fluordeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging detected that the expansion of the tumor volume was delayed (P\u3c0.05) following intra-tumoral (i.t.) injection with 131I-HCuSNPs-MS-PTX plus near-infrared (NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography (SPECT)/photoacoustic imaging mediated by 131I-HCuSNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results revealed that 131I-HCuSNPs-MS-PTX offered combined photothermal, chemo- and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, 131I-HCuSNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model

A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection.

Zika virus (ZIKV) has spread in many countries or territories causing severe neurologic complications with potential fatal outcomes. The small primate common marmosets are susceptible to ZIKV, mimicking key features of human infection. Here, a novel simian adenovirus type 23 vector-based vaccine expressing ZIKV pre-membrane-envelope proteins (Sad23L-prM-E) was produced in high infectious titer. Due to determination of immunogenicity in mice, a single-dose of 3×108 PFU Sad23L-prM-E vaccine was intramuscularly inoculated to marmosets. This vaccine raised antibody titers of 104.07 E-specific and 103.13 neutralizing antibody (NAb), as well as robust specific IFN-γ secreting T-cell response (1,219 SFCs/106 cells) to E peptides. The vaccinated marmosets, upon challenge with a high dose of ZIKV (105 PFU) six weeks post prime immunization, reduced viremia by more than 100 folds, and the low level of detectable viral RNA (103.66) and T-cell response (>726 SFCs/106 PBMCs) were acquired 1-2 weeks post exposure to ZIKV, while non-vaccinated control marmosets developed long-term high titer of ZIKV (105.73 copies/ml) (P<0.05). No significant pathological lesions were observed in marmoset tissues. Sad23L-prM-E vaccine was detectable in spleen, liver and PBMCs at least 4 months post challenge. In conclusion, a prime immunization with Sad23L-prM-E vaccine was able to protect marmosets against ZIKV infection when exposed to a high dose of ZIKV. This Sad23L-prM-E vaccine is a promising vaccine candidate for prevention of ZIKV infection in humans

Prime-boost vaccination of mice and rhesus macaques with two novel adenovirus vectored COVID-19 vaccine candidates.

ABSTRACTCOVID-19 vaccines are being developed urgently worldwide. Here, we constructed two adenovirus vectored COVID-19 vaccine candidates of Sad23L-nCoV-S and Ad49L-nCoV-S carrying the full-length gene of SARS-CoV-2 spike protein. The immunogenicity of two vaccines was individually evaluated in mice. Specific immune responses were observed by priming in a dose-dependent manner, and stronger responses were obtained by boosting. Furthermore, five rhesus macaques were primed with 5 × 109 PFU Sad23L-nCoV-S, followed by boosting with 5 × 109 PFU Ad49L-nCoV-S at 4-week interval. Both mice and macaques well tolerated the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost regimen induced high titers of 103.16 anti-S, 102.75 anti-RBD binding antibody and 102.38 pseudovirus neutralizing antibody (pNAb) at 2 months, while pNAb decreased gradually to 101.45 at 7 months post-priming. Robust T-cell response of IFN-γ (712.6 SFCs/106 cells), IL-2 (334 SFCs/106 cells) and intracellular IFN-γ in CD4+/CD8+ T cell (0.39%/0.55%) to S peptides were detected in vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials

The Role of 18F-FDG PET/CT and MRI in Assessing Pathological Complete Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer: A Systematic Review and Meta-Analysis

Purpose. We performed this meta-analysis to determine the utilities of 18F-FDG PET/CT and MRI in assessing the pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in the same cohort of patients with breast cancer. Methods. Two reviewers systematically searched on PubMed, Scopus, and Springer (from the beginning of 1992 to Aug. 1, 2015) for the eligible articles. Heterogeneity, pooled sensitivity and specificity, positive likelihood ratio, negative likelihood ratio, and the summary receiver operating characteristic (SROC) curve were calculated to estimate the diagnostic efficacy of 18F-FDG PET/CT and MRI. Results. A total of 6 studies including 382 pathologically confirmed patients were eligible. The pooled sensitivity and specificity of 18F-FDG PET/CT were 0.86 (95% CI: 0.76–0.93) and 0.72 (95% CI: 0.49–0.87), respectively. Pooled sensitivity and specificity of MRI were 0.65 (95% CI: 0.45–0.80) and 0.88 (95% CI: 0.75–0.95), respectively. The area under the SROC curve of 18F-FDG PET/CT and MRI was 0.88 and 0.84, respectively. Conclusion. Study indicated that 18F-FDG PET/CT had a higher sensitivity and MRI had a higher specificity in assessing pCR in breast cancer patients. Therefore, the combined use of these two imaging modalities may have great potential to improve the diagnostic performance in assessing pCR after NAC

Lesion based diagnostic performance of dual phase 99mTc-MIBI SPECT/CT imaging and ultrasonography in patients with secondary hyperparathyroidism

Abstract Background We aimed to evaluate the diagnostic performance of 99mTc-MIBI SPECT/CT and ultrasonography in patients with secondary hyperparathyroidism (SHPT), and explored the factors that affect the diagnostic performance. Methods 99mTc-MIBI SPECT/CT and ultrasonography were performed in 50 patients with SHPT within 1 month before they underwent surgery. Imaging results were confirmed by the pathology. Pearson correlation analysis was used to determine the correlation of PTH level with clinical data. The optimal cutoff value for predicting positive 99mTc-MIBI results was evaluated by ROC analysis in lesions diameter. Results Forty-nine patients had a positive 99mTc-MIBI imaging results and 39 patients had positive ultrasonography results. The sensitivities of 99mTc-MIBI and ultrasonography were 98.00% and 78.00%, respectively. A total of 199 lesions were resected in 50 patients. Among them, 183 lesions were proved to be parathyroid hyperplasia. On per-lesion basis analysis, the sensitivity and specificity of 99mTc-MIBI and ultrasonography were 59.34% and 75.00% vs 46.24% and 80.00%, respectively. The Pearson correlation analysis showed that the serum AKP and PTH level had a significant linear association (r = 0.699, P < 0.001). The lesion diameter was a statistically significant predictive factor in predicting positive 99mTc-MIBI SPECT/CT. The optimal cutoff value for predicting positive 99mTc-MIBI results evaluated by ROC analysis in lesions diameter was 8.05 mm. Conclusion Dual phase 99mTc-MIBI SPECT/CT imaging had a higher sensitivity in patients with SHPT than ultrasonography. Therefore, using 99mTc-MIBI positioning the lesion could be an effective method pre-surgical in patients with SHPT

Optimal 18F-FDG PET/CT radiomics model development for predicting EGFR mutation status and prognosis in lung adenocarcinoma: a multicentric study

PurposeTo develop and interpret optimal predictive models to identify epidermal growth factor receptor (EGFR) mutation status and subtypes in patients with lung adenocarcinoma based on multicentric 18F-FDG PET/CT data, and further construct a prognostic model to predict their clinical outcome.MethodsThe 18F-FDG PET/CT imaging and clinical characters of 767 patients with lung adenocarcinoma from 4 cohorts were collected. Seventy-six radiomics candidates using cross-combination method to identity EGFR mutation status and subtypes were built. Further, Shapley additive explanations and local interpretable model-agnostic explanations were used for optimal models’ interpretation. Moreover, in order to predict the overall survival, a multivariate Cox proportional hazard model based on handcrafted radiomics features and clinical characteristics was constructed. The predictive performance and clinical net benefit of the models were evaluated via area under receiver operating characteristic (AUC), C-index and decision curve analysis. ResultsAmong the 76 radiomics candidates, light gradient boosting machine classifier (LGBM) combined with recursive feature elimination wrapped LGBM feature selection method achieved best performance in predicting EGFR mutation status (AUC reached 0.80, 0.61, 0.71 in the internal test cohort and two external test cohorts, respectively). And extreme gradient boosting classifier combined with support vector machine feature selection method achieved best performance in predicting EGFR subtypes (AUC reached 0.76, 0.63, 0.61 in the internal test cohort and two external test cohorts, respectively). The C-index of the Cox proportional hazard model achieved 0.863.ConclusionsThe integration of cross-combination method and the external validation from multi-center data achieved a good prediction and generalization performance in predicting EGFR mutation status and its subtypes. The combination of handcrafted radiomics features and clinical factors achieved good performance in predicting prognosis. With the urgent needs of multicentric 18F-FDG PET/CT trails, robust and explainable radiomics models have great potential in decision making and prognosis prediction of lung adenocarcinoma