Enhanced antitumor immune responses via a new agent [131I]-labeled dual-target immunosuppressant.

Radionuclides theranostic are ideal "partners" for bispecific antibodies to explore the immune response of patients and synergistic treatment. A bispecific single-domain antibody-Fc fusion protein, KN046, exhibits a good treatment effect by binding to programmed cell death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). An ionizing-radiation stimulus mediated by a low-dose of [131I] may be used for immunopotentiation. In this study, we established [131I]-labeled KN046 as a novel radioimmunotherapy agent to treat malignant melanoma and explored the mechanism. METHODS: After intravenous injection of [131I]-KN046, SPECT/CT imaging was applied to identify candidate targets for KN046 immunotherapy. [18F]-FDG and [68 Ga]-NOTA-GZP (granzyme B-specific PET imaging agent) micro-PET/CT imaging was used to assess the immune response in vivo after [131I]-KN046 treatment. The synergistic treatment effect of [131I]-KN046 was evaluated by exploring the [131I]-based radionuclide-induced release of tumor immunogenicity-related antigens as well as the histology and survival of tumor-bearing mice after treatment. RESULTS: The constructed [131I]-KN046 exhibited high affinity and specificity for PD-L1/CTLA-4 immune targets and had excellent in vivo intratumoral retention capability so as to achieve good antitumor efficacy. More importantly, the combination of low-dose [131I] and KN046-enhanced immunosensitivity increased the immunotherapy response rates significantly. Exposure of tumor cells to [131I]-KN046 led to upregulated expression of MHC-I and Fas surface molecules and significant increases in the degree of T-cell activation and counts of tumor-infiltrating immunocytes. CONCLUSION: Use of low-dose [131I] combined with a dual-target immunosuppressant could be exploited to identify the subset of treatment responders but also exhibited great potential for enhancing antitumor immune responses.

A core-shell Au@Cu2-xSe heterogeneous metal nanocomposite for photoacoustic and computed tomography dual-imaging-guided photothermal boosted chemodynamic therapy.

Chemodynamic therapy (CDT) has aroused extensive attention for conquering cancers because of its high specificity and low invasiveness. Quick generation of hydroxyl radicals (·OH) during CDT could induce more irreparable damage to cancer cells. The generation rate of ·OH could be magnified via the selection of suitable nanocatalysts or under the assistance of exogenous thermal energy from photothermal therapy (PTT). Here, we construct a kind of monodisperse core-shell Au@Cu2-xSe heterogeneous metal nanoparticles (NPs) for PTT boosted CDT synergistic therapy. Due to the localized surface plasmon resonance (LSPR) coupling effect in the core-shell structure, the photothermal conversion efficiency of Au@Cu2-xSe NPs is up to 56.6%. The in situ generated heat from photothermal can then accelerate the Fenton-like reaction at Cu+ sites to produce abundant ·OH, which will induce apoptotic cell death by attacking DNA, contributing to a heat-boosted CDT. Both in vitro and in vivo results showed that after this synergistic therapy, tumors could be remarkably suppressed. Guided by photoacoustic (PA) and computed tomography (CT) imaging, the therapeutic effects were more specified. Our results revealed that PA and CT dual-imaging-guided PTT boosted CDT synergistic therapy based on core-shell Au@Cu2-xSe NPs is an effective cancer treatment strategy.

18F-FDG PET/CT radiomic predictors of pathologic complete response (pCR) to neoadjuvant chemotherapy in breast cancer patients.

PURPOSE: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is commonly accepted as the gold standard to assess outcome after NAC in breast cancer patients. 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has unique value in tumor staging, predicting prognosis, and evaluating treatment response. Our aim was to determine if we could identify radiomic predictors from PET/CT in breast cancer patient therapeutic efficacy prior to NAC. METHODS: This retrospective study included 100 breast cancer patients who received NAC; there were 2210 PET/CT radiomic features extracted. Unsupervised and supervised machine learning models were used to identify the prognostic radiomic predictors through the following: (1) selection of the significant (p < 0.05) imaging features from consensus clustering and the Wilcoxon signed-rank test; (2) selection of the most discriminative features via univariate random forest (Uni-RF) and the Pearson correlation matrix (PCM); and (3) determination of the most predictive features from a traversal feature selection (TFS) based on a multivariate random forest (RF). The prediction model was constructed with RF and then validated with 10-fold cross-validation for 30 times and then independently validated. The performance of the radiomic predictors was measured in terms of area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The PET/CT radiomic predictors achieved a prediction accuracy of 0.857 (AUC = 0.844) on the training split set and 0.767 (AUC = 0.722) on the independent validation set. When age was incorporated, the accuracy for the split set increased to 0.857 (AUC = 0.958) and 0.8 (AUC = 0.73) for the independent validation set and both outperformed the clinical prediction model. We also found a close association between the radiomic features, receptor expression, and tumor T stage. CONCLUSION: Radiomic predictors from pre-treatment PET/CT scans when combined with patient age were able to predict pCR after NAC. We suggest that these data will be valuable for patient management.

EFFECT OF POST-SURGICAL RAI THERAPY ON PARATHYROID FUNCTION IN PATIENTS WITH DIFFERENTIATED THYROID CANCER.

Objective: Radiotherapy with radioactive iodine (RAI) has become a common treatment for postsurgical differentiated thyroid carcinoma (DTC). The objective of this study was to determine the effect of RAI therapy following surgery on the function of the parathyroid glands in DTC patients. Methods: A total of 81 DTC patients who received RAI therapy after surgery were enrolled in the study. The size of the residual thyroid was detected by technetium-99m (99mTc)-pertechnetate thyroid scan (99mTc thyroid scan) before RAI therapy. The iodine uptake ability of residual thyroid was evaluated by iodine-131 (131I) whole-body scan (WBS). All patients were treated with an activity of 3.7 GBq (100 mCi) 131I. Parathyroid hormone (PTH), serum calcium, phosphorus, and magnesium were evaluated at 1 day before treatment, and at 1 month and 3 months after treatment. Results: The results show that there was no statistically significant difference in blood PTH level observed (P>.05) between 3 time points (pre-treatment, 1 month post-treatment and 3 months post-treatment). The serum calcium and phosphorus did not change significantly (P>.05), but serum magnesium level was elevated after treatment (P<.05). There were no significant differences between PTH changes and sex, age, scores of 99mTc thyroid scan, scores of 131I WBS, Tumor (T) stage, and Node (N) stage. Conclusion: RAI therapy following surgery did not significantly affect parathyroid function in DTC patients. Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid carcinoma; FT3 = free triiodothyronine; FT4 = free thyroxine; 131I = iodine-131; PTH = parathyroid hormone; RAI = radioiodine; 99mTc = Technetium-99m; TG = thyroglobulin; TNM = Tumor Node Metastasis; TSH = thyroid-stimulating hormone; WBS = whole-body scan.

18F-Deoxyglucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) Monitoring of Dynamic Growth Characteristics of Walker-256 Tumor Models in 3 Different Locations in Rats.

BACKGROUND We explored the ideal method of establishing subcutaneous, breast, and liver tumor models using the same Walker-256 cells, and investigated the dynamic growth characteristics using ¹8F-deoxyglucose (¹8F-FDG) positron emission tomography/computed tomography (PET/CT), which provides basic information for choosing an experimental animal model. MATERIAL AND METHODS We established tumor models in 3 locations (subcutaneous, breast, and liver) in W256 Sprague-Dawley rats. ¹8F-FDG PET/CT imaging was performed from 6 days to 18 days after injecting the cells subcutaneously. Tumor volume of interest (VOI), maximum standard uptake value (SUVmax), and average standard uptake value (SUVavg) were obtained from the image. The difference of the growth characteristics in tumor volume and SUVs among the 3 groups were compared. Histopathology of the tumors was also analyzed. RESULTS The tumors in subcutaneous location grew fastest, followed by tumors located in the breast, and tumors in the liver grew slowest. Significant differences in tumor VOI (p=0.01) were observed. ¹8F-FDG uptake of the subcutaneous and breast tumors increased until day 10 and then decreased subsequently. ¹8F-FDG uptake of the liver tumor reached a peak at day 10, and necrosis peaked at day 12. The histopathology analysis results indicated that the necrosis was mainly located in the center of tumors while the viable tissues were located on the periphery. Similarly, CD 31 and Ki-67 were mainly expressed on the tumor periphery. CONCLUSIONS Subcutaneous, breast, and liver tumor models were easy to establish using Walker-256 cells. They showed fast growth and high uptake of ¹8F-FDG. These kinds of tumor models were optimal in evaluating anti-tumor efficacy by ¹8F-FDG PET/CT, but it may be essential to determine the best time-points at which to use it.

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

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.

Breast-specific gamma camera imaging with 99mTc-MIBI has better diagnostic performance than magnetic resonance imaging in breast cancer patients: A meta-analysis.

OBJECTIVE: This study aimed to evaluate the diagnostic role of breast-specific gamma camera imaging (BSGI) with technetium-99m-methoxy isobutyl isonitrile (99mTc-MIBI) and magnetic resonance imaging (MRI) in patients with breast cancer through a meta-analysis. METHODS: Three reviewers searched articles published in medical journals before June 2016 in MEDLINE, EMBASE and Springer Databases; the references listed in original articles were also retrieved. We used the quality assessment of diagnostic accuracy studies (QUADAS) tool to assess the quality of the included studies. Heterogeneity, pooled sensitivity and specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR) and summary receiver operating characteristic (SROC) curves were calculated by Meta-DiSc software to estimate the diagnostic performance of BSGI and MRI. Ten studies with 517 patients were included after meeting the inclusion criteria. We did a subgroup analysis of the same data type. RESULTS: The pooled sensitivities of BSGI and MRI were: 0.84 (95% CI, 0.79-0.88) and 0.89 (95% CI, 0.84-0.92) respectively, and the pooled specificities of BSGI and MRI were: 0.82 (95% CI, 0.74-0.88) and 0.39 (95% CI, 0.30-0.49) respectively. The areas under the SROC curve of BSGI and MRI were 0.93 and 0.72 respectively. CONCLUSION: The results of our meta-analysis indicated that compared with MRI, BSGI has similar sensitivity, higher specificity, better diagnostic performance, and can be widely used in clinical practice.

Cerebral blood perfusion changes in amputees with myoelectric hands after rehabilitation: a SPECT computer-aided analysis.

BACKGROUND: Rehabilitation, which is essential for amputees with myoelectric hands, can improve the quality of daily life by remodeling the neuron network. In our study, we aim to develop a cerebral blood perfusion (CBF) single-photon emission computed tomography computer-aided (SPECT-CA) detection scheme to automatically locate the brain's activated regions after rehabilitation. RESULTS: Five participants without forearms (three male, two female, mean age 51 ± 12.89 years, two missing the right side, and three missing the left side) were included in our study. In the clinical assessment, all of the participants received higher scores after training. The results of the SPM analysis indicated that CBF in the precentral gyrus, postcentral gyrus, frontal lobe, temporal lobe and cerebellum was significantly different among the five participants (P < 0.05). Moreover, SPECT-CA showed that the activated brain areas mainly included the precentral gyrus, postcentral gyrus, cerebellum and extensive cerebral cortex. CONCLUSION: Our study demonstrated that the CBF SPECT-CA method can detect the brain blood perfusion changes induced by rehabilitation with high sensitivity and accuracy. This method has great potential for locating the remodeled neuron regions of amputees with myoelectric hands after rehabilitation.

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

Purpose: To 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. Methods: The 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. Results: Among 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. Conclusions: The 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.

Improving Breast Tumor Segmentation in PET via Attentive Transformation Based Normalization.

Positron Emission Tomography (PET) has become a preferred imaging modality for cancer diagnosis, radiotherapy planning, and treatment responses monitoring. Accurate and automatic tumor segmentation is the fundamental requirement for these clinical applications. Deep convolutional neural networks have become the state-of-the-art in PET tumor segmentation. The normalization process is one of the key components for accelerating network training and improving the performance of the network. However, existing normalization methods either introduce batch noise into the instance PET image by calculating statistics on batch level or introduce background noise into every single pixel by sharing the same learnable parameters spatially. In this paper, we proposed an attentive transformation (AT)-based normalization method for PET tumor segmentation. We exploit the distinguishability of breast tumor in PET images and dynamically generate dedicated and pixel-dependent learnable parameters in normalization via the transformation on a combination of channel-wise and spatial-wise attentive responses. The attentive learnable parameters allow to re-calibrate features pixel-by-pixel to focus on the high-uptake area while attenuating the background noise of PET images. Our experimental results on two real clinical datasets show that the AT-based normalization method improves breast tumor segmentation performance when compared with the existing normalization methods.

CaCO3 -Encapuslated Microspheres for Enhanced Transhepatic Arterial Embolization Treatment of Hepatocellular Carcinoma.

Transcatheter arterial embolization (TAE) is an extensively applied treatment method for hepatocellular carcinoma (HCC). However, the worsened tumor microenvironment (TME, e.g., reduced pH post-TAE) may result in unsatisfactory therapeutic outcome. Herein, a new kind of embolic agent, calcium carbonate encapsulated alginate microspheres (CaCO3 -ALG MSs) are synthesized. Such CaCO3 -ALG MSs are able to neutralize the tumor pH owing to the reaction of CaCO3 with protons, which would not affect the overall morphology of microspheres after decomposition of CaCO3 . TAE treatment with CaCO3 -ALG MSs is then conducted in an orthotopic rat liver cancer model. 18 F-Fluorodeoxyglucose micropositron emission tomography/computed tomography imaging is conducted post-TAE and discovered that intra-arterial injection of CaCO3 -ALG MSs shows obvious enhanced therapeutic outcome compared to the same treatment with bare ALG MSs or the clinically used lipiodol. Further studies including analysis of immune cells in tumors, cytokine assays, and bioinformatics analysis all verify the reverse of immunosuppressive TME toward a more immunosupportive one after TAE with CaCO3 -ALG MSs. The research not only presents a new CaCO3 -containing embolic agent for enhanced TAE treatment of HCC but also highlights a clinically meaningful approach to improve cancer treatment via tumor pH neutralization.

Highly Tumor-Specific and Long-Acting Iodine-131 Microbeads for Enhanced Treatment of Hepatocellular Carcinoma with Low-Dose Radio-Chemoembolization.

Transarterial radioembolization (TARE) is considered the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Iodine-131 (131I)-labeled lipiodol TARE is an effective treatment for HCC but has been withdrawn due to its poor retention in tumor lesions and significant distribution in normal tissues with severe side effects. In this work, a highly tumor-specific 131I-TARE agent with long-time retention is developed by simply introducing tyrosine to poly(vinyl alcohol) (PVA) drug-eluting microbeads (Tyr-PVA-DEBs). The labeling efficiency of 131I-labeled microbeads remains above 85% in 50% serum for 31 days. Micro-single-photon emission computed tomography/computed tomography (µSPECT/CT) evidences that the 131I-labeled microbeads accumulate in the orthotopic N1S1 hepatoma of rats for 31 days following intra-arterial injection. The cumulative radiation dose per cubic centimeter of the tumor is at least 13 678-fold higher than that of normal tissues. The highly tumor-selective radiation of the 131I-labeled microbeads allows localized delivery of 345.04 ± 139.16 Gy to the tumor following a single injection dose as low as 0.2 mCi of 131I. Moreover, the 131I-labeled microbeads are loaded with doxorubicin hydrochloride (DOX) through the carboxy groups on tyrosine of the polymer. The 131I-DOX-loaded microbeads present a synergetic antitumor effect without recurrence in comparison with the microbeads labeled with 131I or loading DOX alone, attributed to the sensitization of DOX to 131I-induced ionizing radiation damage to DNA under the embolization-induced hypoxia. Our results demonstrate a high tumor retention of 131I-labeled embolic agent for low-dose transarterial radio-chemoembolization (TARCE) with a synergetic therapeutic effect on treating HCC, showing potential for clinical application.

Synthesis and Evaluation of Ga-68-Labeled Rhein for Early Assessment of Treatment-Induced Tumor Necrosis.

PURPOSE: This study aimed to synthesize a necrosis-avid agent using rhein as a precursor and labeled with gallium-68 (Ga-68) for positron emission tomography/computed tomography (PET/CT) imaging, to evaluate response to anticancer treatment in a mouse model. PROCEDURES: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated rhein was radiolabeled with Ga-68 to formulate [68Ga]DOTA-rhein. The in vitro stability of [68Ga]DOTA-rhein was assessed by radio-HPLC. Necrosis avidity was evaluated in a mouse model of muscle necrosis by microPET/CT imaging, biodistribution study, histochemical staining, and autoradiography studies. Murine tumor models with the subcutaneous implantation of S180 cell lines were generated for the evaluation of therapeutic effect. Tumor necrosis was induced by the treatment of combretastatin A4 disodium phosphate (CA4P), and microPET/CT imaging was performed at 1 h post tracer injection. DNA binding studies were conducted to explore the necrosis avidity mechanism of the tracer. RESULTS: [68Ga]DOTA-rhein exhibited a satisfactory yield, a radiochemical purity over 97 %, and a good serum stability. The uptakes of [68Ga]DOTA-rhein in necrotic muscles and tumors were significantly higher than those in normal muscles and tumors (P < 0.05). The results of autoradiography and histochemical staining were consistent with the selective uptake of the radiotracer in necrotic regions. MicroPET/CT images showed a high uptake of the tracer in necrotic muscles and necrotic tumors. DNA binding studies suggested that necrosis avidity correlated with DNA binding to a certain extent. CONCLUSIONS: Our results demonstrated that [68Ga]DOTA-rhein showed a prominent necrosis avidity and could be a useful probe for early assessment of response to anticancer therapy by PET/CT imaging.

Radioactive Iodine Therapy in Patients with Differentiated Thyroid Cancer: Study of External Dose Rate Attenuation Law and Individualized Patient Management.

BACKGROUND: Therapy with radioactive iodine (131I) is a well established treatment method for postsurgical differentiated thyroid carcinoma (DTC). A fixed discharge time is generally set, regardless of individual differences in residual body radioactivity (RBA). This study aimed to investigate the RBA of each patient to find the attenuation law and to identify underlying factors in order to predict the time point for a safe, scientifically sound discharge plan. METHODS: A total of 231 DTC patients undergoing 131I treatment were all treated with 3.7 GBq (100 mCi) of 131I. RBA was estimated by measuring the external body dose rate (EDR) at a distance of 1 m from the body surface between 0 and 72 hours after oral administration of 131I. Data from each patient were used to establish a time-EDR value (h-µSv/h) curve. Software was developed to predict the time when a patient's dose equivalent meets the national safety standard by including six time points between 40 and 60 hours. Several factors that might affect that time were analyzed. RESULTS: The EDR attenuation law in patients could be described with a double exponential decay model, and the cutoff value was set as 23.3 µSv/h, upon which the predictive software was developed. Student's t-test showed there was no statistical difference between predicted values and the actual measured values (p > 0.05). Correlation analysis found that serum thyroglobulin, total triiodothyronine, total thyroxine, free triiodothyronine, free thyroxine, thyrotropin, 2- and 24-hour iodine uptake rate of the thyroid, scores of 99mTc-pertechnetate thyroid scan, scores of 131I whole-body scan, scores of ultrasound scan, and gastrointestinal residues were associated with attenuation speed. A further multiple linear regression analysis found that 24-hour iodine uptake (X1), residual thyroid grading by 131I whole-body scan (X2), blood free triiodothyronine (X3) and free thyroxine (X4) predominantly influenced the decline of the EDR. The regression equation was Y = 2.091X1 + 6.370X2 + 4.529X3 + 2.466X4 - 8.614 (F = 44.03, p < 0.01). CONCLUSIONS: An effective and convenient method was created to measure and predict the individual safety time for discharge. This could play a significant role not only for scientific hospital discharge planning, rational use of medical resources, and better individualized management, but also in public radiation protection.

131I-Labeled Copper Sulfide-Loaded Microspheres to Treat Hepatic Tumors via Hepatic Artery Embolization.

Purpose: Transcatheter hepatic artery embolization therapy is a minimally invasive alternative for treating inoperable liver cancer but recurrence is frequent. Multifunctional agents, however, offer an opportunity for tumor eradication. In this study, we were aim to synthesized poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating hollow CuS nanoparticles (HCuSNPs) and paclitaxel (PTX) that were then labeled with radioiodine-131 (131I) to produce 131I-HCuSNPs-MS-PTX. This compound combines the multi-theranostic properties of chemotherapy, radiotherapy and photothermal therapy. In addition, it can also be imaged with single photon emission computed tomography (SPECT) imaging and photoacoustic imaging. Methods: We investigated the value of therapeutic and imaging of 131I-HCuSNPs-MS-PTX in rats bearing Walker-256 tumor transplanted in the liver. After the intra-arterial (IA) injection of 131I-HCuSNPs-MS-PTX, 18F-Fluorodeoxyglucose (18F-FDG) micro-positron emission tomography/computed tomography (micro-PET/CT) imaging was used to monitor the therapeutic effect. PET/CT findings were verified by immunohistochemical analysis. SPECT/CT and photoacoustic imaging were performed to demonstrate the distribution of 131I-HCuSNPs-MS-PTX in vivo. Results: We found that embolization therapy in combination with chemotherapy, radiotherapy and photothermal therapy offered by 131I-HCuSNPs-MS-PTX completely ablated the transplanted hepatic tumors at a relatively low dose. In comparison, embolization monotherapy or combination with one or two other therapies had less effective anti-tumor efficacy. The combination of SPECT/CT and photoacoustic imaging effectively confirmed microsphere delivery to the targeted tumors in vivo and guided the near-infrared laser irradiation. Conclusion: Our study suggests that there is a clinical theranostic potential for imaging-guided arterial embolization with 131I-HCuSNPs-MS-PTX for the treatment of liver tumors.

The combined therapeutic effects of 131iodine-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<0.05) 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.

The Role of (18)F-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 (18)F-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 (18)F-FDG PET/CT and MRI. RESULTS: A total of 6 studies including 382 pathologically confirmed patients were eligible. The pooled sensitivity and specificity of (18)F-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 (18)F-FDG PET/CT and MRI was 0.88 and 0.84, respectively. CONCLUSION: Study indicated that (18)F-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.

Corrigendum to "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".

[This corrects the article DOI: 10.1155/2016/3746232.].

Fluorine-18-fluorodeoxyglucose positron emission tomography to evaluate recurrent gastric cancer after surgical resection: a systematic review and meta-analysis.

We aimed to explore the diagnostic accuracy of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) for detection of gastric cancer recurrence after surgical resection through a systematic review and meta-analysis. "PubMed", EMBASE, Web of Knowledge and Springer, from the beginning of 2002 to Feb 2015, were searched for studies evaluating the diagnostic performance of 18F-FDG PET in detecting recurrent gastric cancer. We calculated sensitivities, specificities, diagnostic odds ratios and likelihood ratios, and constructed summary receiver operating characteristic curves. Fourteen studies (828 patients) were included. On a per-patient basis, the forest plots showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of (18)F-FDG PET or PET/CT were 0.85 [95 % confidence interval (CI) 0.75-0.92], 0.78 (95 % CI 0.72-0.84), 3.9 (95 % CI 2.9-5.4), 0.19 (95 % CI 0.11-0.34), and 21 (95 % CI 9-47), respectively. On a per-lesion basis, the pooled sensitivity was 0.75 (95 % CI 0.61-0.86). The area under the SROC curve of PET/CT on the basis of per-patient was 0.86. (18)F-FDG PET had great value in the detection of gastric cancer recurrence after surgical resection. The sensitivities of (18)F-FDG PET were 85 and 75 %, respectively, on per-patient basis and on per-lesion basis.

The role of fluorine-18 fluorodeoxyglucose PET in prognosis evaluation for stem cell transplantation of lymphoma: a systematic review and meta-analysis.

The role of fluorine-18 fluorodeoxyglucose PET (F-FDG PET) in prognostic evaluation of pre-stem cell transplantation (SCT) and post-SCT is still uncertain. A systematic review and meta-analysis were carried out to detect the prognostic power of F-FDG PET. 'PubMed', EMBASE, and Springer were searched for relevant articles. Subgroup analysis was carried out to evaluate the F-FDG PET in predicting the prognosis between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma. Finally, 17 studies that included 1192 patients were eligible, 16 studies for progression-free survival (PFS) and 12 studies for overall survival (OS). For the pre-SCT PET or PET/computed tomography scan, the combined hazard ratios (HRs) of PET for PFS and OS were 2.32 and 2.64, respectively. Subgroup analysis showed that the HRs of PFS for HL and non-Hodgkin lymphoma were 3.28 and 2.00, respectively. For the post-SCT PET scan, the combined HR for PFS was 4.61. The sensitivity analysis showed that exlcusion of any single study had no significant effect on HR. We found that F-FDG PET was especially effective in predicting pre-STC and post-STC prognosis. The patients with a negative PET scan had a better prognosis compared with those with a positive scan in PFS and OS. In the subgroup analysis, F-FDG PET had a higher value in predicting prognosis before SCT for HL patients.