Yingjian Zhang

Tungsten oxide nanorods: an efficient nanoplatform for tumor CT imaging and photothermal therapy.

We report here a facile thermal decomposition approach to creating tungsten oxide nanorods (WO2.9 NRs) with a length of 13.1 ± 3.6 nm and a diameter of 4.4 ± 1.5 nm for tumor theranostic applications. The formed WO2.9 NRs were modified with methoxypoly(ethylene glycol) (PEG) carboxyl acid via ligand exchange to have good water dispersability and biocompatibility. With the high photothermal conversion efficiency irradiated by a 980 nm laser and the better X-ray attenuation property than clinically used computed tomography (CT) contrast agent Iohexol, the formed PEGylated WO2.9 NRs are able to inhibit the growth of the model cancer cells in vitro and the corresponding tumor model in vivo, and enable effective CT imaging of the tumor model in vivo. Our “killing two birds with one stone” strategy could be extended for fabricating other nanoplatforms for efficient tumor theranostic applications.

Thermally robust Mo/CoFeB/MgO trilayers with strong perpendicular magnetic anisotropy.

The recent discovery of perpendicular magnetic anisotropy (PMA) at the CoFeB/MgO interface has accelerated the development of next generation high-density non-volatile memories by utilizing perpendicular magnetic tunnel junctions (p-MTJs). However, the insufficient interfacial PMA in the typical Ta/CoFeB/MgO system will not only complicate the p-MTJ optimization, but also limit the device density scalability. Moreover, the rapid decreases of PMA in Ta/CoFeB/MgO films with annealing temperature higher than 300°C will make the compatibility with CMOS integrated circuits a big problem. By replacing the Ta buffer layer with a thin Mo film, we have increased the PMA in the Ta/CoFeB/MgO structure by 20%. More importantly, the thermal stability of the perpendicularly magnetized (001)CoFeB/MgO films is greatly increased from 300°C to 425°C, making the Mo/CoFeB/MgO films attractive for a practical p-MTJ application.

Graphene oxide-BaGdF5 nanocomposites for multi-modal imaging and photothermal therapy

By using a solvothermal method in the presence of polyethylene glycol (PEG), BaGdF5 nanoparticles are firmly attached on the surface of graphene oxide (GO) nanosheets to form the GO/BaGdF5/PEG nanocomposites. The resulting GO/BaGdF5/PEG shows low cytotoxicity, positive magnetic resonance (MR) contrast effect and better X-ray attenuation property than Iohexol, which enables effective dual-modality MR and X-ray computed tomography (CT) imaging of the tumor model in vivo. The enhanced near-infrared absorbance, good photothermal stability and efficient tumor passive targeting of GO/BaGdF5/PEG result in the highly efficient photothermal ablation of tumor in vivo after intravenous injection of GO/BaGdF5/PEG and the following 808-nm laser irradiation (0.5 W/cm(2)). The histological and biochemical analysis data reveal no perceptible toxicity of GO/BaGdF5/PEG in mice after treatment. These results indicate potential application of GO/BaGdF5/PEG in dual-modality MR/CT imaging and photothermal therapy of cancers.

18F-Fluoromisonidazole PET/CT: A Potential Tool for Predicting Primary Endocrine Therapy Resistance in Breast Cancer

Although endocrine therapy is an effective method to treat estrogen receptor (ER)–positive breast cancer, approximately 30%–40% of all hormone receptor–positive tumors display de novo resistance. The aim of our current study was to analyze whether 18F-labeled fluoromisonidazole (1-(2-nitro-1-imidazolyl)-2-hydroxy-3-fluoropropane [18F-FMISO]) PET/CT could predict primary resistance to hormonal therapy in ER-positive breast cancer. Methods: Postmenopausal women who had ER-α–positive breast cancer, stages II–IV, and had never received prior endocrine therapy were prospectively enrolled in this study. Patients underwent both 18F-FDG and 18F-FMISO PET/CT scans before and after treatment. The hottest 18F-FDG standardized uptake value (SUV) in the tumor foci, the SUVs at 2 and 4 h, and the TBR2 h and TBR4 h for the target lesions were calculated (TBR2 h = SUV2 hT/SUV2 hB and TBR4 h = SUV4 hT/SUV4 hB [TBR is the tumor-to-background ratio]). Clinical outcomes of primary endocrine therapy with letrozole were evaluated according to the criteria of the World Health Organization after at least 3 mo of treatment. Immunohistochemistry for markers of proliferation (Ki67) and hypoxia-induced factor 1α was performed on a subset of tumors that had undergone biopsy or surgery. Pearson and Spearman analysis was used to determine the correlation between the parameters of 18F-FDG and 18F-FMISO uptake and clinical or immunohistochemistry outcomes with a 0.01 threshold for statistical significance. Results: A total of 45 lesions (13 primary, 32 metastatic) from 20 patients met the inclusion criteria in this study. Baseline 18F-FDG and 18F-FMISO PET/CT scans were obtained for 33 lesions from 16 patients. The correlation between baseline 18F-FDG uptake and clinical outcome was weak and did not reach statistical significance (r = 0.37, P = 0.031). However, there was a significantly positive correlation between baseline 18F-FMISO uptake (SUV2 hT, TBR2 h, SUV4 hT, and TBR4 h) and clinical outcomes after ≥3 mo of primary endocrine therapy with letrozole (r = 0.77, 0.76, 0.71, and 0.78, respectively; P < 0.0001). The application of a TBR4 h cutoff of ≥1.2 allowed the prediction of 88% of the cases of progressive disease (15/17). Despite poor correlation between 18F-FMISO uptake and hypoxia-induced factor 1α expression, a marginal positive correlation between TBR4 h and Ki67 expression was measured (r = 0.51, P = 0.011) in a subset of malignant lesions acquired by biopsy or surgery. Conclusion: 18F-FMISO PET/CT can be used to predict primary endocrine resistance in ER-positive breast cancer.

Pretreatment (18)F-FDG uptake heterogeneity can predict survival in patients with locally advanced nasopharyngeal carcinoma--a retrospective study.

BackgroundIntratumoural heterogeneity has been demonstrated to be a strong indicator of malignant transformation. Our study was to investigate pretreatment 18 F-FDG parameters, including 18 F-FDG based heterogeneity for predicting survival in patients with locally advanced nasopharyngeal carcinoma (NPC).MethodsForty newly diagnosed, biopsy-proven locally advanced NPC patients who underwent 18 F-FDG PET/CT were retrospectively included. The following PET parameters were assessed: maximum and mean standardised uptake value (SUVmax and SUVmean), metabolic tumour volume (MTV), total lesion glycolysis (TLG) and intratumoral heterogeneity index (HI). The previous parameters were recorded both for the primary tumor (-T) and neck lymph nodes (-N). The following endpoints were evaluated: local control (LC), progression-free survival (PFS) and overall survival (OS). The survival analyses were performed using the Kaplan–Meier method. Univariate analysis was performed using the log-rank test.ResultsPatients with a lower HI-T, SUVmax-T, SUVmean-T and TLG-T had significantly better 2-year LC. In predicting PFS, we found that both lower HI-T and HI-N had significantly better prognosis. However, the OS was only statistically associated with HI-T.Conclusion18 F-FDG based heterogeneity appears to be an potential predicator of patient survival after treatment.

Can Fluorine-18 Fluoroestradiol Positron Emission Tomography–Computed Tomography Demonstrate the Heterogeneity of Breast Cancer In Vivo?

AIM Our study was to investigate the heterogeneity of estrogen receptor (ER) expression among tumor sites by using fluorine-18 ((18)F) fluoroestradiol (FES) positron-emission tomography-computed tomography (PET-CT) imaging. METHODS Thirty-two breast cancer patients underwent both (18)F-FES and (18)F fluorodeoxyglucose (FDG) PET-CTs from June 2010 to December 2011 in our center (mean age, 53 years; range, 27-77 years). We used the maximum standardized uptake value to quantify ER expression and a cutoff value of 1.5 to dichotomize results into ER(+) and ER(-). The difference of heterogeneity between the initial patients and patients with recurrent or metastatic disease after treatments was assessed by using the χ(2) test. Also, the (18)F-FES uptake was compared with the (18)F-FDG uptake by use of Spearman correlation coefficients. RESULTS A total number of 237 lesions in 32 patients were detected. Among them, most lesions (64.1% [152/237]) were bone metastasis. A striking 33.4-fold difference in (18)F-FES uptake was observed among different patients (maximum standardized uptake value range, 0.5 to approximately 16.7), and a 8.2-fold difference was observed among lesions within the same individual (1.0 to approximately 8.2). As for (18)F-FDG uptake, the difference was 11.6-fold (1.3 to approximately 15.1) and 9.9-fold (1.4 to approximately 13.8), respectively. In 28.1% (9/32) of the patients, both (18)F-FES(+) and (18)F-FES(-) metastases were present, which suggests partial discordant ER expression. After treatments, 37.5% (9/24) patients with recurrent or metastatic breast cancer showed heterogeneity, whereas no untreated patient was detected to exist discordant ER expression (χ(2), 4.174; P < .05). In addition, the (18)F-FES uptake showed a weak correlation with the (18)F-FDG uptake (ρ = 0.248; P < .05). CONCLUSION (18)F-FES and (18)F-FDG uptake varied greatly both within and among patients. (18)F-FES PET-CT demonstrated a conspicuous number of patients with the heterogeneity of ER expression.

Prevalence and risk of cancer of incidental uptake in prostate identified by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography

OBJECTIVE The objective was to investigate the prevalence of incidental fluorine-18 fluorodeoxyglucose (FDG) uptake in positron emission tomography/computed tomography. METHODS A total of 11,239 male nonprostate disease patients were included retrospectively. RESULTS The prevalence of incidental prostate FDG uptake was approximately 1.8%. Among 198 incidental lesions, 100 patients had further examinations; 20 lesions were confirmed to be malignant, while 80 lesions were benign. After logistic regression analysis, age, site, and the maximum standard uptake value were the potent predictors for differentiation of malignant prostate lesions. CONCLUSION When focal FDG uptake in the peripheral zone of prostate is detected, especially in elderly men, further clinical evaluation is recommended.

Prevalence and risk of cancer of thyroid incidentaloma identified by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography.

OBJECTIVE To investigate the prevalence and risk of thyroid incidentaloma identified by positron emission tomography/computed tomography (PET/CT). STUDY DESIGN Historical cohort study. SETTING Fudan University Shanghai Cancer Center. METHODS A total of 15 948 non-thyroid disease patients who underwent fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT from November 2006 to September 2010 were included. They were divided into two groups: 12 080 patients for metastatic evaluation and 3868 patients for cancer screening. When thyroid incidentaloma was found, further diagnostic examination was conducted. MAIN OUTCOME MEASURES Prevalence and risk of thyroid incidentaloma. RESULTS The prevalence of incidental thyroid 18F-FDG uptake was approximately 2.5% (395 of 15 948). The prevalence of incidentaloma in healthy subjects (118 of 3868; 3.1%) was statistically higher than that in patients with suspected or known cancer (277 of 12 080; 2.3%) (p < .05). Among 395 incidentalomas, 146 patients had further examinations (53 patients with histologic confirmations, 93 patients with clinical monitoring). Finally, 43 lesions were confirmed to be malignancies. Therefore, the cancer risk was 29.5% (43 of 146), and it was higher in cancer screening patients (24 of 59; 40.7%) than in alleged cancer patients (19 of 87; 21.8%) (p < .05). As for FDG uptake pattern, the prevalence of thyroid cancer was 11.6% (5 of 43) and 36.9% (38 of 103) in the group of patients with diffuse and focal uptake, respectively (p < .05). After logistic regression analysis, age, sex, maximal standardized uptake value, and calcification were the potent predictors of differentiation. CONCLUSION The presence of focal uptake with high SUVmax and calcification detected on CT images correlates with a high likelihood of thyroid malignancy. When a focal thyroid incidentaloma is detected, further examination should be performed.

MR/SPECT Imaging Guided Photothermal Therapy of Tumor-Targeting Fe@Fe3O4 Nanoparticles in Vivo with Low Mononuclear Phagocyte Uptake

The (125)I-c(RGDyK) peptide PEGylated Fe@Fe3O4 nanoparticles ((125)I-RGD-PEG-MNPs) with the average hydrodynamic diameter of ∼40 nm as a novel multifunctional platform were developed for tumor-targeting MR/SPECT imaging guided photothermal therapy in vivo. On the αvβ3-positive U87MG glioblastoma xenograft model, the signals of tumor from T2-weighted MR and SPECT imaging were much higher than those in the blocking group at 6 h post injection (p.i.) of RGD-PEG-MNPs and (125)I-RGD-PEG-MNPs intravenously, respectively. The pharmacokinetics and biodistribution were analyzed quantitatively by gamma counter ex vivo. The fact suggested that RGD-PEG-MNPs exhibited excellent targeting property and low mononuclear phagocyte uptake. At 6 h p.i. for (125)I-RGD-PEG-MNPs, the maximum uptake of 6.75 ± 1.24% of the percentage injected dose per gram (ID/g) was accumulated in the tumor. At 48 h p.i., only 1.11 ± 0.21% and 0.16 ± 0.09% ID/g were accumulated in the liver and spleen, respectively. With the guidance of MR/SPECT imaging, the multifunctional nanoparticles achieved a good photothermal therapeutic efficacy in vivo.

Can Positron Emission Tomography/Computed Tomography with the Dual Tracers Fluorine-18 Fluoroestradiol and Fluorodeoxyglucose Predict Neoadjuvant Chemotherapy Response of Breast Cancer? ----A Pilot Study

Objective To assess the clinical value of dual tracers Positron emission tomography/computed tomography (PET/CT) 18F-fluoroestradiol (18F-FES) and 18F-fluorodeoxyglucose (18F-FDG) in predicting neoadjuvant chemotherapy response (NAC) of breast cancer. Methods Eighteen consecutive patients with newly diagnosed, non-inflammatory, stage II and III breast cancer undergoing NAC were included. Before chemotherapy, they underwent both 18F-FES and 18F-FDG PET/CT scans. Surgery was performed after three to six cycles of chemotherapy. Tumor response was graded and divided into two groups: the responders and non-responders. We used the maximum standardized uptake value (SUVmax) to qualify each primary lesion. Results Pathologic analysis revealed 10 patients were responders while the other 8 patients were non-responders. There was no statistical difference of SUVmax-FDG and tumor size between these two groups (P>0.05). On the contrary, SUVmax-FES was lower in responders (1.75±0.66 versus 4.42±1.14; U=5, P=0.002); and SUVmax-FES/FDG also showed great value in predicting outcome (0.16±0.06 versus 0.54±0.22; U=5, P=0.002). Conclusions Our study showed 18F-FES PET/CT might be feasible to predict response of NAC. However, whether the use of dual tracers 18F-FES and 18F-FDG has complementary value should be further studied.