Methodological and Cellular Factors Affecting the Magnitude of Breast Cancer and Normal Cell Radiosensitization Using Gold Nanoparticles.

Purpose: Breast cancer (BC) is the most common malignant tumor in women, which most often originates from the epithelial tissue of the breast gland. One of the most recommended kinds of treatment is radiotherapy (RT), but irradiation (IR) can affect not only the cancer tumor but also the healthy tissue around it. Au nanoparticles (AuNPs) were proposed as a radiosensitizing agent for RT which would allow for lower radiation doses, reducing the negative radiation effects on healthy tissues. The main objective of the study is to assess the dependence on the radiosensitivity of BC (MDA-MB-231) and normal mammary gland epithelial cells (MCF12A) to ionizing radiation, caused by functionalized AuNPs under diverse conditions. Methods: The viability, uptake, reactive oxygen species induction, and mitochondrial membrane potential in cells were analyzed applying a time and concentration-dependent manner. After different incubation times with AuNPs, cells were exposed to 2 Gy. The determination of radiation effect in combination with AuNPs was investigated using the clonogenic assay, p53, and γH2AX level, as well as, Annexin V staining. Results: Our results highlighted the strong need for assessing the experimental conditions' optimization before the AuNPs will be implemented with IR. Moreover, results indicated that AuNPs did not act universally in cells. Conclusion: AuNPs could be a promising tool as a radiotherapy sensitizing agent, but it should be specified and deeply investigated under what conditions it will be applied taking into consideration not only AuNPs modifications but also the model and experimental conditions.

Value of [18F]FDG PET/CT radiomic parameters in the context of response to chemotherapy in advanced cervical cancer.

The first-order statistical (FOS) and second-order texture analysis on basis of Gray-Level Co-occurence Matrix (GLCM) were obtained to assess metabolic, volumetric, statistical and radiomic parameters of cervical cancer in response to chemotherapy, recurrence and age of patients. The homogeneous group of 83 patients with histologically confirmed IIIC1-IVB stage cervical cancer were analyzed, retrospectively. Before and after chemotherapy, the advancement of the disease and the effectiveness of the therapy, respectively, were established using [18F] FDG PET/CT imaging. The statistically significant differences between pre- and post-therapy parameters were observed for SUVmax, SUVmean, TLG, MTV, asphericity (ASP, p = 0.000, Z > 0), entropy (E, p = 0.0000), correlation (COR, p = 0.0007), energy (En, p = 0.000) and homogeneity (H, p = 0.0018). Among the FOS parameters, moderate correlation was observed between pre-treatment coefficient of variation (COV) and patients' recurrence (R = 0.34, p = 0.001). Among the GLCM textural parameters, moderate positive correlation was observed for post-treatment contrast (C) with the age of patients (R = 0.3, p = 0.0038) and strong and moderate correlation was observed in the case of En and H with chemotherapy response (R = 0.54 and R = 0.46, respectively). All correlations were statistically significant. This study indicates the remarkable importance of pre- and post-treatment [18F] FDG PET statistical and textural GLCM parameters according to prediction of recurrence and chemotherapy response of cervical cancer patients.

Asphericity derived from [18F]FDG PET as a new prognostic parameter in cervical cancer patients.

The objective of this study was to assess the prognostic value of asphericity (ASP) and standardized uptake ratio (SUR) in cervical cancer patients. Retrospective analysis was performed on a group of 508 (aged 55 ± 12 years) previously untreated cervical cancer patients. All patients underwent a pretreatment [18F]FDG PET/CT study to assess the severity of the disease. The metabolic tumor volume (MTV) of the cervical cancer was delineated with an adaptive threshold method. For the resulting ROIs the maximum standardized uptake value (SUVmax) was measured. In addition, ASP and SUR were determined as previously described. Univariate Cox regression and Kaplan-Meier analysis with respect to event free survival (EFS), overall survival (OS), freedom from distant metastasis (FFDM) and locoregional control (LRC) was performed. Additionally, a multivariate Cox regression including clinically relevant parameters was performed. In the survival analysis, MTV and ASP were shown to be prognostic factors for all investigated endpoints. Tumor metabolism quantified with the SUVmax was not prognostic for any of the endpoints (p > 0.2). The SUR did not reach statistical significance either (p = 0.1, 0.25, 0.066, 0.053, respectively). In the multivariate analysis, the ASP remained a significant factor for EFS and LRC, while MTV was a significant factor for FFDM, indicating their independent prognostic value for the respective endpoints. The alternative parameter ASP has the potential to improve the prognostic value of [18F]FDG PET/CT for event-free survival and locoregional control in radically treated cervical cancer patients.

The Role of Functionalization and Size of Gold Nanoparticles in the Response of MCF-7 Breast Cancer Cells to Ionizing Radiation Comparing 2D and 3D In Vitro Models.

Gold nanoparticles (AuNPs), as an agent enhancing radiosensitivity, play a key role in the potential treatment of breast cancer (BC). Assessing and understanding the kinetics of modern drug delivery systems is a crucial element that allows the implementation of AuNPs in clinical treatment. The main objective of the study was to assess the role of the properties of gold nanoparticles in the response of BC cells to ionizing radiation by comparing 2D and 3D models. In this research, four kinds of AuNPs, different in size and PEG length, were used to sensitize cells to ionizing radiation. The in vitro viability, uptake, and reactive oxygen species generation in cells were investigated in a time- and concentration-dependent manner using 2D and 3D models. Next, after the previous incubation with AuNPs, cells were irradiated with 2 Gy. The assessment of the radiation effect in combination with AuNPs was analyzed using the clonogenic assay and γH2AX level. The study highlights the role of the PEG chain in the efficiency of AuNPs in the process of sensitizing cells to ionizing radiation. The results obtained imply that AuNPs are a promising solution for combined treatment with radiotherapy.

Diagnosis and treatment of lung cancer using nuclear medicine techniques - current state of the art.

Lung cancer is the leading cause of cancer-related death worldwide. Planar radiography and computed tomography are the most common imaging modalities used in diagnosis, staging, and therapy response assessment. However, the role of nuclear methods in assessing the severity of the disease and the effectiveness of treatment has increased in recent years. Introducing these diagnostic modalities into standard practice in lung cancer may contribute to the personalization of treatment. In this review, we summarize the current knowledge of nuclear medicine techniques in the diagnosis and treatment of lung cancer.

Prognostic Value of Pretherapeutic Primary Tumor MTV from [18F]FDG PET in Radically Treated Cervical Cancer Patients.

The aim of this study was to assess the usefulness of pretherapeutic primary tumor metabolic tumor volume (MTV) in the prognosis of radically treated cervical cancer patients. Retrospective, single-centre analysis was performed on a group of 508 cervical cancer patients. All patients underwent a pretreatment [18F]FDG PET/CT study for the assessment of the disease stage. Several PET-derived parameters-namely, maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), total lesion glycolysis (TLG) and MTV, as well as the clinical parameters, were analysed in terms of the overall survival (OS), event-free survival (EFS), locoregional control (LRC) and freedom from distant metastases (FFDM). Hyperthermia and brachytherapy were prognostic for EFS, OS, and LRC.FIGO stage > II showed a significant effect on EFS, OS, and FFDM. Moreover, hysterectomy was prognostic for OS and histology was prognostic for FFDM. From the PET-derived parameters only MTV of the primary tumor had a significant influence on OS (cutoff point: >12.7 mL, HR: 2.8, 1.75-4.48 95% CI, p < 0.001), LRC (cutoff point: >13.7 mL, HR 2.82, 1.42-5.61 95% CI, p = 0.003), EFS (cutoff point: >10.4 mL, HR: 2.57, 1.67-3.97 95% CI, p < 0.001) and FFDM (cutoff point: >10.4 mL, HR: 5.04, 1.82-13.99 95% CI, p = 0.002). Pretreatment MTV from the primary tumor is the only independent prognostic parameter in OS, LRC, EFS, and FFDM in radically treated cervical cancer patients and should be used in clinical practice in assessing prognosis in these patients.

Differences between TNM classification and 2-[18F]FDG PET parameters of primary tumor in NSCLC patients.

BACKGROUND: The aim of the study was to compare the TNM classification with 2-[18F]FDG PE T biological parameters of primary tumor in patients with NSCLC. MATERIALS AND METHODS: Retrospective analysis was performed on a group of 79 newly diagnosed NSCLC patients. PET scans were acquired on Gemini TF PET/CT scanner 60-70 min after injection of 2-[18F]FDG with the mean activity of 364 ± 75 MBq, with the area being examined from the vertex to mid-thigh. The reconstructed PET images were evaluated using MIM 7.0 Software for SUVmax, MTV and TLG values. RESULTS: The analysis of the cancer stage according to TNM 8th edition showed stage IA2 in 8 patients, stage IA3 - 6 patients, stage IB - 4 patients, IIA - 3 patients, 15 patients with stage IIB, stage IIIA - 17 patients, IIIB - 5, IIIC - 5, IVA in 7 patients and stage IVB in 9 patients. The lowest TLG values of primary tumor were observed in stage IA2 (11.31 ± 15.27) and the highest in stage IIIC (1003.20 ± 953.59). The lowest value of primary tumor in SUVmax and MTV were found in stage IA2 (6.8 ± 3.8 and 1.37 ± 0.42, respectively), while the highest SUVmax of primary tumor was found in stage IIA (13.4 ± 11.4) and MTV in stage IIIC (108.15 ± 127.24). CONCLUSION: TNM stages are characterized by different primary tumor 2-[18F]FDG PET parameters, which might complement patient outcome.

The Combination of Liposomes and Metallic Nanoparticles as Multifunctional Nanostructures in the Therapy and Medical Imaging-A Review.

Nanotechnology has introduced a new quality and has definitely developed the possibilities of treating and diagnosing various diseases. One of the scientists' interests is liposomes and metallic nanoparticles (LipoMNPs)-the combination of which has introduced new properties and applications. However, the field of creating hybrid nanostructures consisting of liposomes and metallic nanoparticles is relatively little understood. The purpose of this review was to compile the latest reports in the field of treatment and medical imaging using of LipoMNPs. The authors focused on presenting this issue in the direction of improving the used conventional treatment and imaging methods. Most of all, the nature of bio-interactions between nanostructures and cells is not sufficiently taken into account. As a result, overcoming the existing limitations in the implementation of such solutions in the clinic is difficult. We concluded that hybrid nanostructures are used in a very wide range, especially in the treatment of cancer and magnetic resonance imaging. There were also solutions that combine treatments with simultaneous imaging, creating a theragnostic approach. In the future, researchers should focus on the description of the biological interactions and the long-term effects of the nanostructures to use LipoMNPs in the treatment of patients.

Differences among [18F]FDG PET-derived parameters in lung cancer produced by three software packages.

Investigation of differences in derived [18F]FDG PET metabolic and volumetric parameters among three different software programs in lung cancer. A retrospective analysis was performed on a group of 98 lung cancer patients who underwent a baseline [18F]FDG PET/CT study. To assess appropriate delineation methods, the NEMA phantom study was first performed using the following software: Philips EBW (Extended Brilliance Workstation), MIM Software and Rover. Based on this study, the best cut-off methods (dependent on tumour size) were selected, extracted and applied for lung cancer delineation. Several semiquantitative [18F]FDG parameters (SUVmax, SUVmean, TLG and MTV) were assessed and compared among the three software programs. The parameters were assessed based on body weight (BW), lean body mass (LBM) and Bq/mL. Statistically significant differences were found in SUVmean (LBM) between MIM Software and Rover (4.62 ± 2.15 vs 4.84 ± 1.20; p < 0.005), in SUVmean (Bq/mL) between Rover and Philips EBW (21,852.30 ± 21,821.23 vs 19,274.81 ± 13,340.28; p < 0.005) and Rover and MIM Software (21,852.30 ± 21,821.23 vs 19,399.40 ± 10,051.30; p < 0.005), and in MTV between MIM Software and Philips EBW (19.87 ± 25.83 vs 78.82 ± 228.00; p = 0.0489). This study showed statistically significant differences in the estimation of semiquantitative parameters using three independent image analysis tools. These findings are important for performing further diagnostic and treatment procedures in lung cancer patients.

The Role of Gold Nanorods in the Response of Prostate Cancer and Normal Prostate Cells to Ionizing Radiation-In Vitro Model.

To increase the efficiency of therapy via enhancing its selectivity, the usage of gold nanorods (GNR) as a factor sensitizing cancer cells to radiation was proposed. Due to gold nanoparticles' characteristics, the smaller doses of radiation would be sufficient in the treatment, protecting the healthy tissue around the tumor. The aim of this study was to investigate the effect of gold nanorods on cancer and normal prostate cells and the role of nanorods in the cell response to ionizing radiation. The effect was evaluated by measuring the toxicity, cell cycle, cell granularity, reactive oxygen species (ROS) level, and survival fractions. Nanorods showed a strong toxicity dependent on the concentration and incubation time toward all used cell lines. A slight effect of nanorods on the cycle distribution was observed. The results demonstrated that the administration of nanorods at higher concentrations resulted in an increased level of generated radicals. The results of cellular proliferation after irradiation are ambiguous; however, there are noticeable differences after the application of nanorods before irradiation. The obtained results lead to the conclusion that nanorods affect the physiology of both normal and cancer cells. Nanorods might become a potential tool used to increase the effectiveness of radiation treatment.

EPR Oximetry Sensor-Developing a TAM Derivative for In Vivo Studies.

Oxygenation is one of the most important physiological parameters of biological systems. Low oxygen concentration (hypoxia) is associated with various pathophysiological processes in different organs. Hypoxia is of special importance in tumor therapy, causing poor response to treatment. Triaryl methyl (TAM) derivative radicals are commonly used in electron paramagnetic resonance (EPR) as sensors for quantitative spatial tissue oxygen mapping. They are also known as magnetic resonance imaging (MRI) contrast agents and fluorescence imaging compounds. We report the properties of the TAM radical tris(2,3,5,6-tetrachloro-4-carboxy-phenyl)methyl, (PTMTC), a potential multimodal (EPR/fluorescence) marker. PTMTC was spectrally analyzed using EPR and characterized by estimation of its sensitivity to the oxygen in liquid environment suitable for intravenous injection (1 mM PBS, pH = 7.4). Further, fluorescent emission of the radical was measured using the same solvent and its quantum yield was estimated. An in vitro cytotoxicity examination was conducted in two cancer cell lines, HT-29 (colorectal adenocarcinoma) and FaDu (squamous cell carcinoma) and followed by uptake studies. The stability of the radical in different solutions (PBS pH = 7.4, cell media used for HT-29 and FaDu cells culturing and cytotoxicity procedure, full rat blood and blood plasma) was determined. Finally, a primary toxicity test of PTMTC was carried out in mice. Results of spectral studies confirmed the multimodal properties of PTMTC. PTMTC was demonstrated to be not absorbed by cancer cells and did not interfere with luciferin-luciferase based assays. Also in vitro and in vivo tests showed that it was non-toxic and can be freely administrated till doses of 250 mg/kg BW via both i.v. and i.p. injections. This work illustrated that PTMTC is a perfect candidate for multimodal (EPR/fluorescence) contrast agent in preclinical studies.

Overmodulation of projections as signal-to-noise enhancement method in EPR imaging.

A study concerning the image quality in electron paramagnetic resonance imaging in two-dimensional spatial experiments is presented. The aim of the measurements was to improve the signal-to-noise ratio (SNR) of the projections and the reconstructed image by applying modulation amplitude higher than the radical electron paramagnetic resonance linewidth. Data were gathered by applying four constant modulation amplitudes, where one was below 1/3 (Amod = 0.04 mT) of the radical linewidth (ΔBpp = 0.14 mT). Three other modulation amplitude values were used in this experiment, leading to undermodulated (Amod < 1/3 ΔBpp), partially overmodulated (Amod ~ 1/3 ΔBpp) and fully overmodulated (Amod > > 1/3 ΔBpp) projections. The advantages of an applied overmodulation condition were demonstrated in the study performed on a phantom containing four shapes of 1.25 mM water solution of 2, 2, 6, 6-tetramethyl-1-piperidinyloxyl. It was shown that even when the overmodulated reference spectrum was used in the deconvolution procedure, as well as the projection itself, the phantom shapes reconstructed as images directly correspond to those obtained in undermodulation conditions. It was shown that the best SNR of the reconstructed images is expected for the modulation amplitude close to 1/3 of the projection linewidth, which is defined as the distance from the first maximum to the last minimum of the gradient-broadened spectrum. For higher modulation amplitude, the SNR of the reconstructed image is decreased, even if the SNR of the measured projection is increased.