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1.
Adv Mater ; 35(10): e2209603, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36524741

RESUMEN

Glutathione (GSH)-activatable probes hold great promise for in vivo cancer imaging, but are restricted by their dependence on non-selective intracellular GSH enrichment and uncontrollable background noise. Here, a holographically activatable nanoprobe caging manganese tetraoxide is shown for tumor-selective contrast enhancement in magnetic resonance imaging (MRI) through cooperative GSH/albumin-mediated cascade signal amplification in tumors and rapid elimination in normal tissues. Once targeting tumors, the endocytosed nanoprobe effectively senses the lysosomal microenvironment to undergo instantaneous decomposition into Mn2+ with threshold GSH concentration of ≈ 0.12 mm for brightening MRI signals, thus achieving high contrast tumor imaging and flexible monitoring of GSH-relevant cisplatin resistance during chemotherapy. Upon efficient up-regulation of extracellular GSH in tumor via exogenous injection, the relaxivity-silent interstitial nanoprobe remarkably evolves into Mn2+ that are further captured/retained and re-activated into ultrahigh-relaxivity-capable complex by stromal albumin in the tumor, and simultaneously allows the renal clearance of off-targeted nanoprobe in the form of Mn2+ via lymphatic vessels for suppressing background noise to distinguish tiny liver metastasis. These findings demonstrate the concept of holographic tumor activation via both tumor GSH/albumin-mediated cascade signal amplification and simultaneous background suppression for precise tumor malignancy detection, surveillance, and surgical guidance.


Asunto(s)
Albúminas , Glutatión , Imagen por Resonancia Magnética , Nanopartículas del Metal , Sondas Moleculares , Neoplasias , Glutatión/administración & dosificación , Glutatión/farmacocinética , Glutatión/farmacología , Sondas Moleculares/administración & dosificación , Sondas Moleculares/farmacocinética , Sondas Moleculares/farmacología , Albúminas/administración & dosificación , Albúminas/farmacocinética , Albúminas/farmacología , Imagen por Resonancia Magnética/métodos , Medios de Contraste/administración & dosificación , Medios de Contraste/farmacocinética , Medios de Contraste/farmacología , Aumento de la Imagen/métodos , Holografía/métodos , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/fisiología , Nanopartículas del Metal/administración & dosificación , Transferrina/administración & dosificación , Transferrina/farmacocinética , Transferrina/farmacología , Distribución Tisular , Células A549 , Humanos , Animales , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Cisplatino/administración & dosificación , Cisplatino/farmacocinética , Cisplatino/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología
2.
Front Oncol ; 11: 792456, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35127499

RESUMEN

PURPOSE: To compare the performance of radiomics to that of the Prostate Imaging Reporting and Data System (PI-RADS) v2.1 scoring system in the detection of clinically significant prostate cancer (csPCa) based on biparametric magnetic resonance imaging (bpMRI) vs. multiparametric MRI (mpMRI). METHODS: A total of 204 patients with pathological results were enrolled between January 2018 and December 2019, with 142 patients in the training cohort and 62 patients in the testing cohort. The radiomics model was compared with the PI-RADS v2.1 for the diagnosis of csPCa based on bpMRI and mpMRI by using receiver operating characteristic (ROC) curve analysis. RESULTS: The radiomics model based on bpMRI and mpMRI signatures showed high predictive efficiency but with no significant differences (AUC = 0.975 vs 0.981, p=0.687 in the training cohort, and 0.953 vs 0.968, p=0.287 in the testing cohort, respectively). In addition, the radiomics model outperformed the PI-RADS v2.1 in the diagnosis of csPCa regardless of whether bpMRI (AUC = 0.975 vs. 0.871, p= 0.030 for the training cohort and AUC = 0.953 vs. 0.853, P = 0.024 for the testing cohort) or mpMRI (AUC = 0.981 vs. 0.880, p= 0.030 for the training cohort and AUC = 0.968 vs. 0.863, P = 0.016 for the testing cohort) was incorporated. CONCLUSIONS: Our study suggests the performance of bpMRI- and mpMRI-based radiomics models show no significant difference, which indicates that omitting DCE imaging in radiomics can simplify the process of analysis. Adding radiomics to PI-RADS v2.1 may improve the performance to predict csPCa.

3.
Abdom Radiol (NY) ; 45(12): 4142-4149, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32902659

RESUMEN

PURPOSE: The studies comparing the versions 2 vs. 2.1 of the Prostate Imaging Reporting and Data System (PI-RADS) are rare. This study aimed to evaluate whether PI-RADS version 2.1 is superior in detecting transition zone prostate cancer in comparison with PI-RADS version 2. METHODS: This was a diagnostic study of patients with prostate diseases who visited the Urology Department of The Second Affiliated Hospital of Soochow University and underwent a magnetic resonance imaging (MRI) examination between 03-01-2016 and 10-31-2018. The images originally analyzed using PI-RADS version 2 were retrospectively re-analyzed and scored in 2019 according to the updated PI-RADS version 2.1. The kappa and receiver operating characteristic (ROC) curves were used. RESULTS: For Reader 1, compared with PI-RADS version 2, version 2.1 had higher sensitivity (85% vs. 79%, P = 0.03), lower specificity (65% vs. 83%, P < 0.001), and lower area under the curve (AUC) (0.749 vs. 0.809, P < 0.001). For Reader 2 (first attempt), compared with PI-RADS version 2, version 2.1 had lower specificity (67% vs. 91%, P < 0.001) and lower AUC (0.702 vs. 0.844, P < 0.001). For Reader 2 (second attempt), compared with PI-RADS version 2, version 2.1 had higher sensitivity (88% vs. 78%, P < 0.001) and lower specificity (77% vs. 91%, P < 0.001). The kappa between the two attempts for Reader 2 was 0.321. CONCLUSION: These results suggest that PI-RADS version 2.1 might improve the detection of prostate cancers in the transition zone compared with PI-RADS version 2 but that it might results in higher numbers of biopsies because of lower specificity.


Asunto(s)
Imagen por Resonancia Magnética , Neoplasias de la Próstata , Biopsia , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Estudios Retrospectivos
4.
Transl Androl Urol ; 9(3): 1252-1261, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32676408

RESUMEN

BACKGROUND: Prostate Imaging Reporting and Data System version 2 (PI-RADS V2) 3 category lesions are of intermediate status with an equivocal risk of presenting clinically significant prostate cancer (csPCa). How to avoid excessive biopsies while improving the csPCa detection rate in these lesions has always been a clinical problem that needed to be solved. The purpose of this study is to explore the csPCa diagnostic value of clinical and magnetic resonance imaging (MRI) data for peripheral and transitional zone (PZ and TZ, respectively) PI-RADS 3 lesions to aid in clinical decision-making and reduce excessive biopsies. METHODS: From March 2016 to October 2018, a total of 629 men who underwent a prostate MRI and subsequently biopsy were enrolled. Two radiologists (with 3 and 7 years of experience, respectively) independently reviewed and scored all images using the PI-RADS V2 scoring criteria. Clinical and MRI data of men with PI-RADS 3 index lesions were collected by another radiologist. Univariate and multivariate analyses were performed to identify the risk factors of csPCa. RESULTS: In a subset of 121 men with 121 PI-RADS 3 index lesions, 25.6% of the lesions (31/121) were PCa (Gleason score ≥6), and 11.6% (14/121) were csPCa (Gleason score ≥7). Further, 44.6% of lesions (54/121) were located in the PZ and 55.4% (67/121) in the TZ. For PZ lesions, 18.5% of the lesions (10/54) were csPCa. Prostate-specific antigen density (PSAD) (P=0.024) and age (P=0.026) were independent risk factors for csPCa in the multivariate logistic analysis. The combination of PSAD and age yielded an area under the curve (AUC) value of 0.816 for predicting csPCa. If biopsy had been restricted to patients with a PSAD ≥0.15 ng/mL2 or an age >68 years, 24.1% (13/54) of patients would have avoided biopsy but only 1 (10%) csPCa would have been missed, with a sensitivity of 80.0% and negative predictive value (NPV) of 92.3%. For TZ lesions, only 6.0% of the lesions (4/67) were csPCa. The PSA and PSAD values in the PI-RADS 3 TZ lesions were higher in the csPCa group (45.07 and 0.47 ng/mL2, respectively) than in the non-csPCa group (10.03 and 0.17 ng/mL2, respectively). CONCLUSIONS: CsPCa was detected at a relatively high rate in PI-RADS 3 PZ lesions. Combining PSAD and age could help to reduce excessive biopsies of such lesions. CsPCa is unlikely to be detected in PI-RADS 3 TZ lesions; thus, active surveillance may be an optimal choice for these lesions, especially among patients without high-risk factors.

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