Purpose Dynamic contrast-enhanced-MRI (DCE-MRI) can provide information regarding tumor perfusion and permeability and has shown prognostic value in certain tumors types. The goal of the present study was to assess the prognostic value of pretreatment DCE-MRI in head and neck squamous cell carcinoma (HNSCC) patients with nodal disease undergoing chemoradiation therapy or surgery. Methods and Materials Seventy-four patients with histologically proven squamous cell carcinoma and neck nodal metastases were eligible for the study. Pretreatment DCE-MRI was performed on a 1.5T MRI. Clinical follow-up was a minimum of 12 months. DCE-MRI data were analyzed using Tofts model. DCE-MRI parameters were related to treatment outcome (progression free survival [PFS] and overall survival [OS]). Patients were grouped as no evidence of disease (NED), alive with disease (AWD), dead with disease (DOD) or dead of other causes (DOC). Prognostic significance was assessed using the log rank test for single variables and Cox proportional hazards regression for combinations of variables. Results At last clinical follow-up, for stage III, all 12 pts were NED, for stage IV, 43 patients were NED, 4 were AWD, 11 were DOD, and 4 were DOC. Ktrans is volume transfer constant. In a stepwise Cox regression skewness of Ktrans was the strongest predictor for stage IV patients (PFS and OS: p<0.001). Conclusion Our study shows that skewness of Ktrans was the strongest predictor of PFS and OS in stage IV HNSCC patients with nodal disease. This study suggests an important role for pretreatment DCE-MRI parameter Ktrans as a predictor of outcome in these patients.

In vivo knowledge of the spatial distribution of viable, necrotic, and hypoxic areas can provide prognostic information about the risk of developing metastases and regional radiation sensitivity and may be used potentially for localized dose escalation in radiation treatment. In this study, multimodality in vivo magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging using stereotactic fiduciary markers in the Dunning R3327-AT prostate tumor were performed, focusing on the relationship between dynamic contrast-enhanced (DCE) MRI using Magnevist (Gd-DTPA) and dynamic (18)F-fluoromisonidazole ((18)F-Fmiso) PET. The noninvasive measurements were verified using tumor tissue sections stained for hematoxylin/eosin and pimonidazole. To further validate the relationship between (18)F-Fmiso and pimonidazole uptake, (18)F digital autoradiography was performed on a selected tumor and compared with the corresponding pimonidazole-stained slices. The comparison of Akep values (kep = rate constant of movement of Gd-DTPA between the interstitial space and plasma and A = amplitude in the two-compartment model (Hoffmann U, Brix G, Knopp MV, Hess T and Lorenz WJ (1995). Magn Reson Med 33, 506-514) derived from DCE-MRI studies and from early (18)F-Fmiso uptake PET studies showed that tumor vasculature is a major determinant of early (18)F-Fmiso uptake. A negative correlation between the spatial map of Akep and the slope map of late (last 1 hour of the dynamic PET scan) (18)F-Fmiso uptake was observed. The relationships between DCE-MRI and hematoxylin/eosin slices and between (18)F-Fmiso PET and pimonidazole slices confirm the validity of MRI/PET measurements to image the tumor microenvironment and to identify regions of tumor necrosis, hypoxia, and well-perfused tissue.

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A deep penetrating and pH-responsive composite nanosystem was strategically developed to improve the efficacy of synergetic photothermal/photodynamic therapy (PTT/PDT) against hypoxic tumor. The designed nanosystem ([PHC]­PP@HA NPs) was constructed by coloading hemoglobin (Hb) and chlorin e6 on polydopamine to build small-sized PHC NPs, which were encapsulated inside the polymer micelles (poly­(ethylene glycol)–poly­(ethylenimine)) and then capped with functionalized hyaluronic acid. The pH-responsive feature made [PHC]­PP@HA NPs retain an initial size of ∼140 nm in blood circulation but rapidly release small PHC NPs (∼10 nm) with a high tumor-penetrating ability in the tumor microenvironment. The in vitro penetration experiment showed that the penetration depth of PHC NPs in the multicellular tumor spheroids exceeded 110 μm. The [PHC]­PP@HA NPs exhibited excellent biocompatibility, deep tumor permeability, high photothermal conversion efficiency (47.09%), and low combination index (0.59) under hypoxic conditions. Notably, the nanosystem can freely adjust the release of oxygen and damaging PHC NPs in an on-demand manner on the basis of the feedback of tumor activity. This feedback tumor therapy significantly improved the synergistic effect of PTT/PDT and reduced its toxic side effects. The in vivo antitumor results showed that the tumor inhibition rate of [PHC]­PP@HA NPs with an on-demand oxygen supply of Hb was ∼100%, which was much better than those of PTT alone and Hb-free nanoparticles ([PC]­PP@HA NPs). Consequently, the [PHC]­PP@HA NP-mediated PTT/PDT guided by feedback tumor therapy achieved an efficient tumor ablation with an extremely low tumor recurrence rate (8.3%) 60 d later, indicating the versatile potential of PTT/PDT.

Long blood circulation in vivo remains a challenge to dual-drug-loaded nanocarriers for synergistic chemotherapy. Herein, a novel strategy to prepare lollipop-like dual-drug-loaded nanoparticles (DOX-PDAgossypol NPs) is developed based on the self-assembly of gossypol, doxorubicin (DOX), and polydopamine (PDA) via π-π stacking. Dopamine polymerizes to PDA and fills the gaps between the gossypol and DOX molecules to form the super compact long-circulating nanoparticles. The DOX-PDA-gossypol NPs show a suitable particle size of 59.6 ± 9.6 nm, high drug loading of 91%, superb stability, high maximum-tolerated dose (MTD) of over 60 mg kg -1 , and negligible toxicity. These NPs also exhibit pH-dependent drug release and low combination index (0.23). Notably, they show dramatically ultralong blood circulation (>192 h) with elimination half times 458-fold and 258-fold longer than that of free DOX and free gossypol, respectively. These values are markedly higher than most of the reported results. Therefore, the DOX-PDA-gossypol NPs have a high tumor accumulation of 12% remaining on the 8th day postinjection. This characteristic contributes to the excellent tumor comprehensive synergistic therapeutic efficacy (TIR > 90%) with low administration dosage and is benefitted for widening the drug therapeutic window. Thus, the proposed strategy has remarkable potential for tumor synergistic therapy.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adfm.201805582. Recent studies have developed various methods to prolong the blood circulation of NCS. These methods mainly include the surface modification of hydrophilic polymers or nonionic Tumor Therapy