Radiosensitization with metallic nanoparticles under MeV proton beams: local dose enhancement.

In addition to specific dosimetric properties of protons, their higher biological effectiveness makes them superior to X-rays and gamma radiation, in radiation therapy. In recent years, enrichment of tumours with metallic nanoparticles as radiosensitizer agents has generated high interest, with several studies attempting to confirm the efficacy of nanoparticles in proton therapy. In the present study Geant4 Monte Carlo (MC) code was used to quantify the increased nanoscopic dose deposition of 50 nm metallic nanoparticles including gold, bismuth, iridium, and gadolinium in water upon exposure to 5, 25, and 50 MeV protons. Dose enhancement factors, radial dose distributions in nano-scale, as well as secondary electron and photon energy spectra were calculated for the studied nanoparticles and proton beams. The obtained results demonstrated that in the presence of metallic nanoparticles an increase in proton energy leads to a decrease in secondary electron and photon production yield. Additionally, an increase in the radial dose enhancement factor from 1.4 to 16 was calculated for the studied nanoparticles when the proton energy was increased from 5 to 50 MeV. It is concluded that the dosimetric advantages of proton beams could be improved significantly in the presence of metallic nanoparticles.

Radiation-induced dormancy of intracerebral melanoma: endotoxin inflammation leads to both shortened tumor dormancy and long-term survival with localized senescence.

Radiation therapy (RT) treats approximately half of all cancers and most brain cancers. RT is variably effective at inducing a dormant tumor state i.e. the time between RT and clinical recurrence of tumor growth. Interventions that significantly lengthen tumor dormancy would improve long-term outcomes. Inflammation can promote the escape of experimental tumors from metastatic dormancy in the lung. Previously we showed intracerebral B16F10 melanoma dormancy varied with RT dose; 20.5 Gy induced dormancy lasted ~ 2 to 4 weeks-sufficient time to study escape from dormancy. Tumors were followed over time using bioluminescence. Surprisingly, some tumors in endotoxin-treated mice exited from dormancy slower; a large fraction of the mice survived more than 1-year. A cohort of mice also experienced an accelerated exit from dormancy and increased mortality indicating there might be variation within the tumor or inflammatory microenvironment that leads to both an early deleterious effect and a longer-term protective effect of inflammation. Some of the melanin containing cells at the site of the original tumor were positive for senescent markers p16, p21 and ßGal. Changes in some cytokine/chemokine levels in blood were also detected. Follow-up studies are needed to identify cytokines/chemokines or other mechanisms that promote long-term dormancy after RT.

Nanoscopic biodosimetry using plasmid DNA in radiotherapy with metallic nanoparticles.

Nanoscopic lesions (complex damages), are the most lethal lesions for the cells. As nanoparticles have become increasingly popular in radiation therapy and the importance of analyzing nanoscopic dose enhancement has increased, a reliable tool for nanodosimetry has become indispensable. In this regard, the DNA plasmid is a widely used tool as a nanodosimetry probe in radiobiology and nano-radiosensitization studies. This approach is helpful for unraveling the radiosensitization role of nanoparticles in terms of physical and physicochemical effects and for quantifying radiation-induced biological damage. This review discusses the potential of using plasmid DNA assays for assessing the relative effects of nano-radiosensitizers, which can provide a theoretical basis for the development of nanoscopic biodosimetry and nanoparticle-based radiotherapy.

The use of the normal tissue non-complication probability (NTCP0) methodology as a new alternative of assessing side-effects in brachytherapy treatments.

Background: The NTCP methodology evaluating side-effects (S-Es) was initially used in radiotherapy (RT), and later was extended to brachytherapy (BT). The NTCP0 methodology has been recently introduced in RT. Given the advantages, this methodology could replace NTCP. Materials and methods: Revisions of studies related to use of NTCP in the evaluations of S-Es in BT. Development of the first versions of two Matlab applications of the NTCP0 methodology. These applications have three options. Two of them employ the well-known aspects of a phenomenological model, or the probabilistic relationship between NTCP0 and total NTCP (TNTCP) that is the sum(NTCP(x i )) i: i th complication i:1..nc: Number of complications; where NTCP0 = 100% - TNTCP; and the third option assumes a NTCP(xi) discrete probabilistic distribution generated by the binomial distribution, where one of its parameters is automatically obtained from a databased of the Disease locations Vs. Late complications. Results: The NTCP0cal and NTCP0calDr Matlab applications have been developed, and respectively used for fractional continuous low dose-rate BT. Conclusions: NTCP0 is defined as the ratio of the number of patients without acute/late complications and total of them, and also can be obtained using our Matlab applications. NTCP0 works do not disregard the last 10-15 years of NTCP research; but NTCP0 was not considered during these years. A generic example was used for showing the variations of the late complications and NTCP0 for a BT treatment of a constant number of fractions and six different dose per fraction values.

Shielding characteristics of nanocomposites for protection against X- and gamma rays in medical applications: effect of particle size, photon energy and nano-particle concentration.

In recent decades, nanomaterials have been extensively investigated for many applications. Composites doped with different metal nanoparticles have been suggested as effective shielding materials to replace conventional lead-based materials. The use of concretes as structural and radiation protective material has been influenced by the addition of nanomaterials. Several elements with high atomic number and density, such as lead, bismuth, and tungsten, have the potential to form nanoparticles that offer significant enhancements in the shielding ability of composites. Their performance for a range of particle concentrations, particle sizes, and photon energies have been investigated. This review is an attempt to gather the data published in the literature about the application of nanomaterials in radiation shielding, including the use of polymer composites and concretes for protection against X-rays and gamma radiation.

Induction of immunogenic cell death and enhancement of the radiation-induced immunogenicity by chrysin in melanoma cancer cells.

Chrysin is a natural flavonoid with anti-cancer effects. Despite its beneficial effects, little information is available regarding its immunogenic cell death (ICD) properties. In this work, we hypothesized that chrysin can potentiate radiotherapy(RT)-induced immunogenicity in melanoma cell line (B16-F10). We examined the effects of chrysin alone and in combination with radiation on ICD induction in B16-F10 cells. Cell viability was assessed using an MTT assay. Cell apoptosis and calreticulin (CRT) exposure were determined using flow cytometry. Western blotting and ELISA assay were employed to examine changes in protein expression. Combination therapy exhibited a synergistic effect, with an optimum combination index of 0.66. The synergistic anti-cancer effect correlated with increased cell apoptosis in cancer cells. Compared to the untreated control, chrysin alone and in combination with RT induced higher levels of DAMPs, such as CRT, HSP70, HMGB1, and ATP. The protein expression of p-STAT3/STAT3 and PD-L1 was reduced in B16-F10 cells exposed to chrysin alone and in combination with RT. Conditioned media from B16-F10 cells exposed to mono-and combination treatments elicited IL-12 secretion in dendritic cells (DCs), inducing a Th1 response. Our findings revealed that chrysin could induce ICD and intensify the RT-induced immunogenicity.

Effect of anode angle on photon beam spectra and depth dose characteristics for X-RAD320 orthovoltage unit.

BACKGROUND: In radiation therapy with orthovoltage units, the tube design has a crucial effect on its dosimetric features. AIM: In this study, the effect of anode angle on photon beam spectra, depth dose and photon fluence per initial electron was studied for a commercial orthovoltage unit of X-RAD320 biological irradiator. MATERIALS AND METHODS: The MCNPX MC code was used for modeling in the current study. We used the Monte Carlo method to model the X-RAD320 X-ray unit based on the manufacturer provided information. The MC model was validated by comparing the MC calculated photon beam spectra with the results of SpekCalc software. The photon beam spectra were calculated for anode angles from 15 to 35 degrees. We also calculated the percentage depth doses for some angles to verify the impact of anode angle on depth dose. Additionally, the heel effect and its relation with anode angle were studied for X-RAD320 irradiator. RESULTS: Our results showed that the photon beam spectra and their mean energy are changed significantly with anode angle and the optimum anode angle of 30 degrees was selected based on less heel effect and appropriate depth dose and photon fluence per initial electron. CONCLUSION: It can be concluded that the anode angle of 30 degrees for X-RAD320 unit used by manufacturer has been selected properly considering the heel effect and dosimetric properties.

The use of the normal tissue non-complication probability (NTCP0) in the safety evaluations as a new alternative of assessing the side-effects of the radiation oncology treatments.

PURPOSE: To encourage the use of the NTCP0 for evaluating safety as a new alternative of assessing the S-Es of the radiation oncology treatments; and the use of the 'NTCP0cal' methodology that calculates/estimates NTCP0. METHOD: Revisions of studies related to use of the NTCP in the evaluations of S-Es. Development of the first version of the Matlab application of our methodology, which provides three options, two of them employ the well-known aspects of a phenomenological model, or the relationship with the TNTCP; where NTCP0 = 100%-TNTCP; and the third option determines NTCP0 from an assumed NTCP discrete probabilistic distribution from the binomial distribution, where one of its parameters is automatically defined from a databased of the Disease locations Vs. Late complications. RESULT: As result of revisions of some QUANTEC studies, we can say that: (1) The majority of current NTCP models are DVH-based; (2) The risk of toxicity is the way of evaluating the S-Es of the radiation oncology treatments; and (3) The NTCP are used mainly for evaluations of individual or principal complications or Endpoints of the radiation treatments. The 'NTCP0cal' Matlab application developed in this study has three calculation options. Two of the options provide additional graphical information about the distributions. CONCLUSIONS: The NTCP0 is a new radiobiological concept, its introduction let to correct some current P + and UTCP formulations, and will allow evaluating S-Es in whatever activity involving ionizing radiation, like radiation treatments; and its phenomenological model function of dose prescribed (D = n*d) will allow calculating values of NTCP0 for a range of dose per fraction (d) in a treatment with a determined number of fractions (n), or for range of n for a constant d. The DVH is irrelevant for this model. For whatever radiation treatment given to a population of similar patients under similar circumstances, the NTCP0 is calculated as ratio of the number of patients without acute/late complications and total of them. When this number is unknown, then NTCP0 can be obtained using the 'NTCP0cal' application.

The effect of nanoparticle coating on biological, chemical and biophysical parameters influencing radiosensitization in nanoparticle-aided radiation therapy.

Nanoparticle-based composites have the potential to meet requirements for radiosensitization in both therapeutic and diagnostic applications. The radiosensitizing properties of nanoparticles could be reliant on the nature of their coating layer. Any gains in reduced toxicity and aggregation or improved delivery to tumor cells for coated nanoparticles must be weighed against the loss of dose enhancement. The radiosensitization potential of coated NPs is confirmed by numerous studies but in most of them, the coating layer is mostly applied to reduce toxicity of the NPs and for stability and biocompatibility aims. While the direct effects of the coating layer in radiosensitization-were ignored and not considered. This review provides an overview of double-edged impact of nanoparticle coating on the radiosensitization potential of nanostructures and discusses the challenges in choosing appropriate coating material in the aim of achieving improved radioenhancement. Coating layer could affect the radiosensitization processes and thereby the biological outcomes of nanoparticle-based radiation therapy. The physicochemical properties of the coating layer can be altered by the type of the coating material and its thickness. Under low-energy photon irradiation, the coating layer could act as a shield for nanoparticles capable of absorb produced low-energy electrons which are important levers for local and nanoscopic dose enhancement. Also, it seems that the coating layer could mostly affect the chemical process of ROS production rather than the physicochemical process. Based on the reviewed literature, for the irradiated coated nanoparticles, the cell survival and viability of cancer cells are decreased more than normal cells. Also, cell cycle arrest, inhibition of cell proliferation, DNA damage, cell death and apoptosis were shown to be affected by coated metallic nanoparticles under irradiation.

A new analytical formula for neutron capture gamma dose calculations in double-bend mazes in radiation therapy.

BACKGROUND: Photoneutrons are produced in radiation therapy with high energy photons. Also, capture gamma rays are the byproduct of neutrons interactions with wall material of radiotherapy rooms. AIM: In the current study an analytical formula was proposed for capture gamma dose calculations in double bend mazes in radiation therapy rooms. MATERIALS AND METHODS: A total of 40 different layouts with double-bend mazes and a 18 MeV photon beam of Varian 2100 Clinac were simulated using MCNPX Monte Carlo (MC) code. Neutron capture gamma ray dose equivalent was calculated by the MC method along the maze and at the maze entrance door of all the simulated rooms. Then, all MC resulted data were fitted to an empirical formula for capture gamma dose calculations. Wu-McGinley analytical formula for capture gamma dose equivalent at the maze entrance door in single-bend mazes was also used for comparison purposes. RESULTS: For capture gamma dose equivalents at the maze entrance door, the difference of 2-11% was seen between MC and the derived equation, while the difference of 36-87% was found between MC and the Wu-McGinley methods. CONCLUSION: Our results showed that the derived formula results were consistent with the MC results for all of 40 different geometries. However, as a new formula, further evaluations are required to validate its use in practical situations. Finally, its application is recommend for capture gamma dose calculations in double-bend mazes to improve shielding calculations.

Optical and NMR dose response of N-isopropylacrylamide normoxic polymer gel for radiation therapy dosimetry.

BACKGROUND: Application of less toxic normoxic polymer gel of N-isopropyl acrylamide (NIPAM) for radiation therapy has been studied in recent years. AIM: In the current study the optical and NMR properties of NIPAM were studied for radiation therapy dosimetry application. MATERIALS AND METHODS: NIPAM normoxic polymer gel was prepared and irradiated by 9 MV photon beam of a medical linac. The optical absorbance was measured using a conventional laboratory spectrophotometer in different wavelengths ranging from 390 to 860 nm. R 2 measurements of NIPAM gels were performed using a 1.5 T scanner and R 2-dose curve was obtained. RESULTS: Our results showed R 2 dose sensitivity of 0.193 ± 0.01 s(-1) Gy(-1) for NIPAM gel. Both R 2 and optical absorbance showed a linear relationship with dose from 1.5 to 11 Gy for NIPAM gel dosimeter. Moreover, absorbance-dose response varied considerably with light wavelength and highest sensitivity was seen for the blue part of the spectrum. CONCLUSION: Our results showed that both optical and NMR approaches have acceptable sensitivity and accuracy for dose determination with NIPAM gel. However, for optical reading of the gel, utilization of an optimum optical wavelength is recommended.

Accelerated brachytherapy with the Xoft electronic source used in association with iodine, gold, bismuth, gadolinium, and hafnium nano-radioenhancers.

PURPOSE: The current study was designed to calculate the dose enhancement factor (DEF) of iodine (I), gold (Au), bismuth (Bi), gadolinium (Gd), and hafnium (Hf) nanoparticles (NP)s by Monte Carlo (MC) modeling of an electronic brachytherapy source in resection cavities of breast tumors. METHODS AND MATERIALS: The GEANT4 MC code was used for simulation of a phantom containing a water-filled balloon and a Xoft source (50 kVp) to irradiate the margins of a resected breast tumor. NPs with a diameter of 20 nm and concentrations from 1 to 5% w/w were simulated in a tumor margin with 5 mm thickness as well as a hypothetical breast model consisting of spherical island-like residual tumor-remnants. The DEFs for all NPs were calculated in both models. RESULTS: In the margin-loaded model, for the concentration of 1% w/w heavy atom, DEFs of 2.5, 2.3, 2.1, 2, and 1.7 were calculated for Bi, Au, I, Hf, and Gd NPs (descending order), which increased, almost linearly with concentration for all NPs. Moreover, normal tissue dose behind the NP-loaded margin declined significantly depending on NP type and concentration. When modeling residual tumor islands, DEF values were very close to the margin-loaded values except for Bi and I, where DEFs of 2.55 and 1.7 were seen, respectively. CONCLUSIONS: Considerable dose enhancements were obtained for the heavy atom NPs studied in the partial breast brachytherapy with a Xoft electronic source. In addition, normal tissue doses were lowered in the points beyond the NP-loaded margin. The findings revealed promising outcomes and the probability of improved tumor control for NP-aided brachytherapy with the Xoft electronic source.

Radiobiological modeling of acute esophagitis after radiation therapy of head, neck, and thorax tumors: The influence of chemo-radiation.

Aim: The aim of this study was to evaluate the performance of various radiobiological models in predicting the occurrence of acute esophagitis (AE) during radiation therapy (RT) of head, neck, and thoracic tumors with concurrent and sequential chemotherapy. According to recent studies, the probability of AE following RT by normal tissue complication probability models is predictable. Materials and Methods: A total of 100 patients with nasopharynx, larynx, Hodgkin's lymphoma, spinal metastases, and oral cavity and lung tumors were included in the study. Half of these patients were treated by concurrent chemo-radiotherapy (Con. CRT) and the other half were treated by radiotherapy alone or sequential chemo-radiotherapy (RT + seq. CRT). Radiobiological models of several types were used as follows,: Lyman-generalized equivalent uniform dose (gEUD), Lyman-MED, log-logistic, logit, and logistic. Parameters were estimated using maximum likelihood estimation, and models were compared using Akaike information criteria. Results: Based on follow-up data, the behavior of dose-response curves differed markedly between the Con. CRT and RT + seq. CRT groups. The best fit with clinical results was offered by the Lyman-MED model for the Con. CRT group and the Lyman-gEUD model for the RT + seq. CRT group. Depending on the model used, the parameter of D50 was considerably lower (up to three times) in the Con. CRT group compared to the RT + seq. CRT group. Conclusions: The incidence of AE significantly differed between the two treatment groups in all the models. New parameter estimates could be used for predicting the probability of acute esophagitis after chemo-RT.

Predicting the Risk of Radiation Pneumonitis and Pulmonary Function Changes after Breast Cancer Radiotherapy.

BACKGROUND: Radiotherapy plays an important role in the treatment of breast cancer. In the process of radiotherapy, the underling lung tissue receives higher doses from treatment field, which led to incidence of radiation pneumonitis. OBJECTIVE: The present study aims to evaluate the predictive factors of radiation pneumonitis and related changes in pulmonary function after 3D-conformal radiotherapy of breast cancer. MATERIAL AND METHODS: In prospective basis study, thirty-two patients with breast cancer who received radiotherapy after surgery, were followed up to 6 months. Respiratory symptoms, lung radiologic changes and pulmonary function were evaluated. Radiation pneumonitis (RP) was graded according to common terminology criteria for adverse events (CTCAE) version 3.0. Dose-volume parameters, which included percentage of lung volume receiving dose of d Gy (V5-V50) and mean lung dose (MLD), were evaluated for RP prediction. Pulmonary function evaluated by spirometry test and changes of FEV1 and FVC parameters. RESULTS: Eight patients developed RP. Among the dose-volume parameters, V10 was associated to RP incidence. When V10<40% and V10≥40% the incidences of RP were 5.26% and 61.54%, respectively. The FEV1 and FVC had a reduction 3 and 6 months after radiotherapy, while only FEV1 showed significant reduction. The FEV1 had more reduction in the patients who developed RP than patients without RP (15.25±3.81 vs. 9.2±0.93). CONCLUSION: Pulmonary function parameters, especially FEV1, significantly decreased at 3 and 6 months after radiotherapy. Since most patients with breast cancer who developed RP did not show obvious clinical symptoms, so spirometry test is beneficial to identify patients with risk of radiation pneumonitis.

A review on gold nanoparticles radiosensitization effect in radiation therapy of cancer.

In the recent years, application of nanoparticles in diagnosis and treatment of cancer has been the issue of extensive research. Among these studies some have focused on the dose enhancement effect of gold nanoparticles (GNPs) in radiation therapy of cancer. On the other hand, some studies indicated energy dependency of dose enhancement effect, and the others have studied the GNP size effect in association with photon energy. However, in some aspects of GNP-based radiotherapy the results of recent studies do not seem very conclusive in spite of relative agreement on the basic physical interaction of photoelectric between GNPs and low energy photons. The main idea behind the GNP dose enhancement in some studies is not able to explain the results especially in recent investigation on cell lines and animal models radiation therapy using GNPs. In the present article the results of the available reports and articles were analyzed and compared and the final status of the GNP-RT was discussed.

A review on photoneutrons characteristics in radiation therapy with high-energy photon beams.

In radiation therapy with high-energy photon beams (E > 10 MeV) neutrons are generated mainly in linacs head thorough (γ,n) interactions of photons with nuclei of high atomic number materials that constitute the linac head and the beam collimation system. These neutrons affect the shielding requirements in radiation therapy rooms and also increase the out-of-field radiation dose of patients undergoing radiation therapy with high-energy photon beams. In the current review, the authors describe the factors influencing the neutron production for different medical linacs based on the performed measurements and Monte Carlo studies in the literature.

Normoxic polymer gel dosimetry using less toxic monomer of N-isopropyl acrylamide and X-ray computed tomography for radiation therapy applications.

BACKGROUND: Polymer gel dosimetry has been used extensively in radiation therapy for its capability in depicting a three dimensional view of absorbed dose distribution. However, more studies are required to find less toxic and more efficient polymers for application in radiotherapy dosimetry. AIM: The purpose of this work was to evaluate the N-isopropyl acrylamide (NIPAM) gel dosimetric characteristics and optimize the protocol for X-ray computed tomography (CT) imaging of gel dosimeters for radiation therapy application. MATERIAL AND METHODS: A polymer gel dosimeter based on NIPAM monomer was prepared and irradiated with (60)Co photons. The CT number changes following irradiation were extracted from CT images obtained with different sets of imaging parameters. RESULTS: The results showed the dose sensitivity of ΔN CT (H) = 0.282 ± 0.018 (H Gy(-1)) for NIPAM gel dosimeter. The optimized set of imaging exposure parameters was 120 kVp and 200 mA with the 10 mm slice thickness. Results of the depth dose measurement with gel dosimeter showed a great discrepancy with the actual depth dose data. CONCLUSION: According to the current study, NIPAM-based gel dosimetry with X-ray CT imaging needs more technical development and formulation refinement to be used for radiation therapy application.

Design and fabrication of a Nano-based neutron shield for fast neutrons from medical linear accelerators in radiation therapy.

BACKGROUND: Photo-neutrons are produced at the head of the medical linear accelerators (linac) by the interaction of high-energy photons, and patients receive a whole-body-absorbed dose from these neutrons. The current study aimed to find an efficient shielding material for fast neutrons. METHODS: Nanoparticles (NPs) of Fe3O4 and B4C were applied in a matrix of silicone resin to design a proper shield against fast neutrons produced by the 18 MeV photon beam of a Varian 2100 C/D linac. Neutron macroscopic cross-sections for three types of samples were calculated by the Monte Carlo (MC) method and experimentally measured for neutrons of an Am-Be source. The designed shields in different concentrations were tested by MCNPX MC code, and the proper concentration was chosen for the experimental test. A shield was designed with two layers, including nano-iron oxide and a layer of nano-boron carbide for eliminating fast neutrons. RESULTS: MC simulation results with uncertainty less than 1% showed that for discrete energies and 50% nanomaterial concentration, the macroscopic cross-sections for iron oxide and boron carbide at the energy of 1 MeV were 0.36 cm- 1 and 0.32 cm- 1, respectively. For 30% nanomaterial concentration, the calculated macroscopic cross-sections for iron oxide and boron carbide shields for Am-Be spectrum equaled 0.12 cm- 1 and 0.15 cm- 1, respectively, while they are 0.15 cm- 1 and 0.18 cm- 1 for the linac spectrum. In the experiment with the Am-Be spectrum, the macroscopic cross-sections for 30% nanomaterial concentration were 0.17 ± 0.01 cm- 1 for iron oxide and 0.21 ± 0.02 cm- 1 for boron carbide. The measured transmission factors for 30% nanomaterial concentration with the Am-Be spectrum were 0.71 ± 0.01, 0.66 ± 0.02, and 0.62 ± 0.01 for the iron oxide, boron carbide, and double-layer shields, respectively. In addition, these values were 0.74, 0.69, and 0.67, respectively, for MC simulation for the linac spectrum at the same concentration and thickness of 2 cm. CONCLUSION: Results achieved from MC simulation and experimental tests were in a satisfactory agreement. The difference between MC and measurements was in the range of 10%. Our results demonstrated that the designed double-layer shield has a superior macroscopic cross-section compared with two single-layer nanoshields and more efficiently eliminates fast photo-neutrons.

Proposals of models for new formulations of the current complication-free cure (P+) and uncomplicated tumor control probability (UTCP) concepts, and total normal tissue complication probability of late complications.

This study proposes phenomenological models for total normal tissue complication probability (TNTCP) and NTCP0. NTCP0 is a new acronym for reformulating the current complication-free cure (P+) and uncomplicated tumor control probability (UTCP) concepts, and TNTCP will reformulate the current NTCP involving multiple organs at risks. The current probabilistic concepts are incoherently formulated with mathematical operations of tumor control probability (TCP) and normal tissue complication probability (NTCP) that are associated with different stochastic processes and random variables. NTCP0 is equal to NTCP0 (normal tissue non-complication probability) that is calculated as the ratio of a number of patients of a population without late complications and a total of them. As a cumulative distribution function (CDF) of late complications, TNTCP = sum(NTCPi), where NTCPi is the NTCP of the ith late complication. TNTCP is also a new acronym, and the probabilistic complement of NTCP0, then NTCP0 = 100% - TNTCP. The NTCP0/TNTCP (D(d)) proposing models are based on the relationship between the NTCP0/TNTCP and total dose (D = n×d; where d = dose per fraction, and n = number of fractions). TNTCP(D) model will be correlated with LKB model (the normal CDF) that is an increasing function; and NTCP0(D) model with a decreasing function, which additionally will define clear limits of three possible regions for NTCP0: 0 and 100% deterministic, and a stochastic. These models are function D, which is widely used for characterizing radiation therapies.

In vitro and in vivo characteristics of doxorubicin-loaded cyclodextrine-based polyester modified gadolinium oxide nanoparticles: a versatile targeted theranostic system for tumour chemotherapy and molecular resonance imaging.

ß-Cyclodextrine-based polyester was coated on the surface of gadolinium oxide nanoparticles (NPs) and then functionalised with folic acid to produce an efficient pH-sensitive targeted theranostic system (Gd2O3@PCD-FA) for doxorubicin delivery and magnetic resonance imaging (MRI). Gd2O3@PCD-FA was fully characterised by FTIR, vibrating sample magnetometer, TGA, XRD, SEM and TEM analyses. The dissolution profile of DOX showed a pH sensitive release. No significant toxicity was observed for the targeted NPs (Gd2O3@PCD-FA) and DOX-loaded NPs inhibiting M109 cells viability more efficiently than free DOX. Moreover, the negligible hemolytic activity of the targeted NPs showed their appropriate hemocompatibility. The preferential uptake was observed for the developed Gd2O3@PCD-FA-DOX NPs in comparison with Dotarem using T1- and T2-weighted MRI in the presence of folate receptor-positive and folate receptor-negative cancer cells (M109 and 4T1, respectively). Furthermore, in vivo studies revealed that Gd2O3@PCD-FA-DOX not only exhibited considerably relaxivity performance as a contrast agent for MRI, but also improved in vivo anti-tumour efficacy of the system. The results suggest that Gd2O3@PCD-FA-DOX improves its therapeutic efficacy in the treatment of solid tumours and also reduces the adverse effects, so it could be proposed as a promising drug delivery system for chemotherapy and molecular imaging diagnosis in MRI.