Review on Isatin- A Remarkable Scaffold for Designing Potential Therapeutic Complexes and Its Macrocyclic Complexes with Transition Metals.

Role of synthetic coordination chemistry in pharmaceutical science is expeditiously increased due to its sundry relevances in this field. The present review endows the synthesized macrocyclic complexes of transition metal ions containing isatin and its derivatives as ligand precursors, their characterization and their copious pharmaceutical applications. Isatin (1H-Indole-2,3-dione) is a protean compound (presence of lactam and keto moiety permits to change its molecular framework) that can be obtained from marine animals, plants, and is also found in mammalian tissues and in human fluids as a metabolite of amino acids. It can be used for the synthesis of miscellaneous organic and inorganic complexes and for designing of drugs since it has remarkable utility in pharmaceutical industry due to its wide range of biological and pharmacological activities, for instance anti-microbial, anti-HIV, anti-tubercular, anti-cancer, anti-viral, anti-oxidant, anti-inflammatory, anti-angiogenic, analgesic activity, anti-Parkinson's disease, anti-convulsant etc. This review provides extensive information about the latest methods for the synthesis of isatin or its substituted derivatives based macrocyclic complexes of transition metals and their plentiful applications in medicinal chemistry.

Assessment of Surface and Build-up Doses for a 6 MV Photon Beam using Parallel Plate Chamber, EBT3 Gafchromic Films, and PRIMO Monte Carlo Simulation Code.

Background: Accurate assessment of surface and build-up doses has a key role in radiotherapy, especially for the superficial lesions with uncertainties involved while performing measurements in the build-up region. Objective: This study aimed to assess surface and build-up doses for 6 MV photon beam from linear accelerator using parallel plate ionization chamber, EBT3 Gafchromic films, and PRIMO Monte Carlo (MC) simulation code. Material and Methods: In this experimental study, parallel plate chamber (PPC05) and EBT3 Gafchromic films were used to measure doses in a build-up region for 6 MV beam from the linear accelerator for different field sizes at various depths ranging from 0 to 2 cm from the surface with 100 cm source to surface distance (SSD) in a solid water phantom. Measured results were compared with Monte Carlo simulated results using PENELOPE-based PRIMO simulation code for the same setup conditions. Effect of gantry angle incidence and SSD were also analyzed for depth doses at the surface and build-up regions using PPC05 ion chamber and EBT3 Gafchromic films. Results: Doses measured at the surface were 14.78%, 19.87%, 25.83%, and 31.54% for field sizes of 5×5, 10×10, 15×15, and 20×20 cm2, respectively for a 6 MV photon beam with a parallel plate chamber and 14.20%, 19.14%, 25.149%, and 30.90%, respectively for EBT3 Gafchromic films. Both measurement sets were in good agreement with corresponding simulated results from the PRIMO MC simulation code; doses increase with the increase in field sizes. Conclusion: Good agreement was observed between the measured depth doses using parallel plate ionization chamber, EBT3 Gafchromic films, and the simulated depth doses using PRIMO Monte Carlo simulation code.

Dosimetric Evaluation of the Treatment Plan on Indigenous Heterogeneous Phantoms using Analytical Anisotropic Algorithm and Acuros-XB Algorithm for Different Photon Energies.

Background: Modern radiotherapy techniques are using advanced algorithms; however, phantoms used for quality assurance have homogeneous density; accordingly, the development of heterogeneous phantom mimicking human body sites is imperative to examine variation between planned and delivered doses. Objective: This study aimed to analyze the accuracy of planned dose by different algorithms using indigenously developed heterogeneous thoracic phantom (HT). Material and Methods: In this experimental study, computed tomography (CT) of HT was done, and the density of different parts was measured. The plan was generated on CT images of HCP with 6 and 15 Megavoltage (MV) photon beams using different treatment techniques, including three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). Plans were delivered by the linear accelerator, and the dose was measured using the ion chamber (IC) placed in HT; planned and measured doses were compared. Results: Density patterns for different parts of the fabricated phantom, including rib, spine, scapula, lung, chest wall, and heart were 1.849, 1.976, 1.983, 0.173, 0.855, and 0.833 g/cc, respectively. Variation between planned and IC estimated doses with the tolerance (±5%) for all photon energies using different techniques. Acuros-XB (AXB) showed a slightly higher variation between computed and IC estimated doses using HCP compared to the analytical anisotropic algorithm (AAA). Conclusion: The indigenous heterogeneous phantom can accurately simulate the dosimetric scenario for different algorithms (AXB or AAA) and be also utilized for routine patient-specific QA.

Dose Agreement Analysis of Treatment Planning System-Calculated Doses and Markus Chamber-Measured Doses in the Near-Surface Region for Breast Cancer Patients' Conformal Treatment Plans.

Background: Surface/skin dose measurement is one of the most challenging tasks for clinical dosimetry in radiotherapy and comparison with almost all the commercially available treatment planning systems (TPSs) brings a significant variation with the measured dose. Aims and Objectives: In the current study, doses calculated from the TPS in the near-surface region for conformal plans (both three-dimensional conformal radiotherapy [3DCRT] and intensity-modulated radiotherapy [IMRT]) of 35 breast cancer patients were evaluated and compared with the doses measured with Markus chamber. Materials and Methods: The computed tomography (CT) images of a solid water slab phantom with a Markus chamber (at different depths ranging from 1 mm to 5 mm from the surface) were taken and imported into the TPS. All the conformal treatment plans made in TPS were executed on a linear accelerator and dose agreements between TPS calculated and chamber measured doses were analysed. Results: Results showed that this TPS underestimated the calculated doses in the superficial region by up to 26% and 21%, respectively, with respect to mean and maximum dose values obtained within the effective volume of the chamber used. Conclusion: The uncertainty of doses in the superficial region should be kept in mind when evaluating treatment plans for superficial tumours in TPS.

Dosimetric validation of Acuros® XB algorithm for RapidArc™ treatment technique: A post software upgrade analysis.

AIM: To validate the Acuros® XB (AXB) algorithm in Eclipse treatment planning system (TPS) for RapidArc™ (RA) technique following the software upgrades. MATERIALS AND METHODS: A Clinac-iX (2300CD) linear accelerator and Eclipse TPS (Varian Medical System, Inc., Palo Alto, USA) was used for commissioning of AXB algorithm using a 6 megavolts photon beam. Percentage depth dose (PDD) and profiles for field size 2 cm × 2 cm, 4 cm × 4 cm, 6 cm × 6 cm, 10 cm × 10 cm, 20 cm × 20 cm, 30 cm × 30 cm to 40 cm × 40 cm were taken. AXB calculated PDDs and profiles were evaluated against the measured and analytical anisotropic algorithm (AAA)-calculated PDDs and profiles. Test sites recommended by American Association of Physicists in Medicine task group (AAPM TG)-119 recommendation were used for RA planning and delivery verification using AXB algorithm.Dosimetric analysis of AXB calculated data showed that difference between calculated and measured data for PDD curves were maximum <1% beyond the depth of dose maximum and computed profiles in central region matches with maximum <1% for all considered field sizes. Ion-chamber measurements showed that the average confidence limit (CLs) was 0.034 and 0.020 in high-gradient and 0.047 and 0.042 in low-gradient regions, respectively, for AAA and AXB calculated RA plans. Portal measurements show the average CLs were 2.48 and 2.58 for AAA and AXB-calculated RA plans, with gamma passing criteria of 3%/3 mm. CONCLUSIONS: AXB shows excellent agreement with measurements and AAA calculated data. The CLs were consistent with the baseline values published by TG-119. AXB algorithm has the potential to perform photon dose calculation with comparable fast calculation speed without negotiating the accuracy. AAPM TG-119 was successfully implemented to access the proper configuration of AXB algorithm following the TPS upgrade.

A study on prostate movement and dosimetric variation because of bladder and rectum volumes changes during the course of image-guided radiotherapy in prostate cancer.

AIM: To study the impact of bladder and rectum volume changes on prostate positioning and the dosimetric parameters. BACKGROUND: Prostate is a moving organ, and its position is also affected by bladder and rectum volumes. Image-guided radiotherapy (IGRT) is being practiced widely for the treatment of prostate carcinoma (Ca). So, it is important to accurately study the effect of bladder and rectum volume changes in treatment. MATERIALS AND METHODS: Thirty patients with Ca prostate were included in this study, and all were treated with 50 Gray (Gy) in 25 fractions for the first phase of treatment. A total of 750 cone-beam computed tomography (CBCT) sessions were performed. Prostate position w.r.t. its day one position was noted, and the bladder and rectum volumes were compared with their volumes on day one. Also, repeat CT was done for five patients after 10 fractions. The initial plan was imported as it was on the repeat CT images, and a hybrid plan was prepared by putting the plan isocenter at the relative anatomical reference point in repeat CT images as it was in primary CT images. The multileaf collimators (MLC) fluence was put as it is, and the dose was calculated using the monitoring units (MU), which were in the initial plan. Doses to bladder, rectum, and the target were analyzed. RESULTS: The mean prostate motion in lateral and anterior-posterior direction was found to be 0.71 (±0.69) centimeter cm) and 0.77 (±0.57) cm, respectively. The mean change in bladder and rectum volumes as compared to that in day one CT images was found to be 110.51 (±84.25) cubic centimeters (cc) and 10.89 (±10.17) cc, respectively. No significant variation was observed in the doses to bladder, rectum, and the target volume in a hybrid plan, as compared to that in actual initial plan. CONCLUSIONS: Bladder and rectum volume affects the position of prostate, rather the dosimetric parameters, and therefore, it can be concluded that daily CBCT should be done for accurate IGRT delivery to the prostate cancer.

Demineralization of tooth enamel following radiation therapy; An in vitro microstructure and microhardness analysis.

OBJECTIVE: The objective of this study is to evaluate the effects of radiotherapy doses on mineral density and percentage mineral volume of human permanent tooth enamel. MATERIALS AND METHODS: Synchrotron radiation Xray microcomputed tomography (SRµCT) and microhardness testing were carried out on 8 and 20 tooth samples, respectively. Enamel mineral density was derived from SRµCT technique using ImageJ software. Microhardness samples were subjected to Vickers indentations followed by calculation of microhardness and percentage mineral volume values using respective mathematical measures. Data were analyzed using paired t-test at a significance level of 5%. Qualitative analysis of the enamel microstructure was done with two-dimensional projection images and scanned electron micrographs using µCT and field emission scanning electron microscopy, respectively. RESULTS: Vickers microhardness and SRµCT techniques showed a decrease in microhardness and an increase in mineral density, respectively, in postirradiated samples. These changes were related to mineral density variation and alteration of hydroxyapatite crystal lattice in enamel surface. Enamel microstructure showed key features such as microporosities and loss of smooth homogeneous surface. These indicate tribological loss and delamination of enamel which might lead to radiation caries. CONCLUSIONS: Tooth surface loss might be a major contributing factor for radiation caries in head-and-neck cancer patients prescribed to radiotherapy. Such direct effects of radiotherapy cause enamel abrasion, delamination, and damage to the dentinoenamel junction. Suitable measures should, therefore, be worked out to protect nontarget oral tissues such as teeth while delivering effective dosages to target regions.

A prospective observational study to analyse the influence of bladder and rectal volume changes on prostate radiotherapy using IMRT.

AIM: To analyse the interfractional bladder and rectal volume changes and the influence on prostate position. BACKGROUND: Interfractional displacement of prostate due to variation in bladder and rectal volume is usual. It is only rational to study the bladder and rectal volume changes and their effects on prostate position during intensity modulated radiotherapy of prostate cancer. MATERIALS AND METHODS: A prospective study was conducted on twenty patients with localized prostate cancer during the first phase of radiotherapy, where 50 gray in 25 fractions was delivered by the IMRT technique with daily cone beam computed tomography Bladder and rectum volumes were delineated on CBCT images and their volumes were noted. Prostate position was noted on each set of CBCT images with respect to specific reference points defined on the ileum and coccyx, and daily prostate displacement was noted. RESULTS: Mean setup errors in vertical, longitudinal and lateral directions were noted as 1.49, 0.498 and 0.17 cm, respectively. Mean change in bladder and rectal volumes in daily CBCT images with respect to that on the first day CT images was noted as 101.94 and 10.22, respectively. Mean lateral and vertical displacement in prostate position was noted as 0.53 and 0.49 cm respectively. No considerable changes in dosimetric parameters were observed because of bladder and rectal volume changes. CONCLUSIONS: Daily CBCT should be done for accurate treatment delivery by the IMRT technique for prostate radiotherapy as prostate shifts physiologically with changes in rectal and bladder volumes.

A Dosimetric Study on Slab-pinewood-slab Phantom for Developing the Heterogeneous Chest Phantom Mimicking Actual Human Chest.

The aim is to study the density, isodose depths, and doses at different points in slab-pinewood-slab (SPS) phantom, solid phantom SP34 (made up of polystyrene), and chest level of actual patient for developing heterogeneous chest phantom mimicking thoracic region of human body. A 6 MV photon beam of field size of 10 cm × 10 cm was directed perpendicular to the surface of computed tomography (CT) images of chest level of patient, SPS phantom, and SP34 phantom. Dose was calculated using anisotropic analytical algorithm. Hounsfield units were used to calculate the density of each medium. Isodose depths in all the three sets of CT images were measured. Variations between planned doses on treatment planning system (TPS) and measured on linear accelerator (LA) were calculated for three points, namely, near slab-pinewood interfaces (6 and 18 cm depths) and 10 cm depth in SPS phantom and at the same depths in SP34 phantom. Density of pinewood, SP34 slabs, chest wall, lung, and soft tissue behind lung was measured as 0.329 ± 0.08, 0.999 ± 0.02, 0.898 ± 0.02, 0.291 ± 0.12, and 1.002 ± 0.03 g/cc, respectively. Depths of 100% and 90% isodose curves in all the three sets of CT images were found to be similar. Depths of 80%, 70%, 60%, 50%, and 40% isodose lines in SPS phantom images were found to be equivalent to that in chest images, while it was least in SP34 phantom images. Variations in doses calculated at 6, 10, and 18 cm depths on TPS and measured on LA were found to be 0.36%, 1.65%, and 2.23%, respectively, in case of SPS phantom, while 0.24%, 0.90%, and 0.93%, respectively, in case of SP34 slab phantom. SPS phantom seemed equivalent to the chest level of human body. Dosimetric results of this study indicate that patient-specific quality assurance can be done using chest phantom mimicking thoracic region of human body, which has been fabricated using polystyrene and pinewood.

Dosimetric analysis of Co-60 source based high dose rate (HDR) brachytherapy: A case series of ten patients with carcinoma of the uterine cervix.

AIM: To analyse the dosimetric parameters of Co-60 based high dose rate (HDR) brachytherapy plans for patients of carcinoma uterine cervix. BACKGROUND: Co-60 high dose rate (HDR) brachytherapy unit has been introduced in past few years and is gaining importance owing to its long half life, economical benefits and comparable clinical outcome compared to Ir-192 HDR brachytherapy. MATERIALS AND METHODS: A study was conducted on ten patients with locally advanced carcinoma of the uterine cervix (Ca Cx). Computed tomography (CT) images were taken after three channel applicator insertions. The planning for 7 Gray per fraction (7 Gy/#) was done for Co-60 HDR brachytherapy unit following the American Brachytherapy Society (ABS) guidelines. All the patients were treated with 3# with one week interval between fractions. RESULTS: The mean dose to high risk clinical target volumes (HRCTV) for D90 (dose to 90% volume) was found to be 102.05% (Standard Deviation (SD): 3.07). The mean D2cc (dose to 2 cubic centimeter volume) of the bladder, rectum and sigmoid were found to be 15.9 Gy (SD: 0.58), 11.5 Gy (SD: 0.91) and 4.1 Gy (SD: 1.52), respectively. CONCLUSION: The target coverage and doses to organs at risk (OARs) were achieved as per the ABS guidelines. Hence, it can be concluded that the Co-60 HDR brachytherapy unit is a good choice especially for the centers with a small number of brachytherapy procedures as no frequent source replacement is required like in an Ir-192 HDR unit.

A study on the necessity of kV-CBCT imaging compared to kV-orthogonal portal imaging based on setup errors: considering other socioeconomical factors.

PURPOSE: Evaluation of setup accuracy in kV-orthogonal portal imaging (OPI)-based and kV-CBCT-based radiotherapy treatment and to find out the necessity of cone-beam computed tomography (CBCT) compared to OPI. MATERIALS AND METHODS: A retrospective study was carried out on 30 patients, who received radiotherapy to the Brain, Head and Neck, and Pelvis. In the OPI technique, anterior-posterior and right-lateral portal images were taken by the On Board Imaging (OBI) system and were superimposed on the reference images. Similarly, in the kV-CBCT technique, CBCT was performed by the OBI system and CBCT images were superimposed on the reference CT images. A total of 150 comparison sets of kV-OPI and kV-CBCT images were analyzed and evaluated. Shifts in the Lateral, Longitudinal, and Vertical directions were noted in both techniques. The iso displacement vector (IDV) was calculated for all imaging. RESULTS: The mean IDV (in cm) are found to be 0.3395 (SD: 0.1477) and 0.3088 (SD: 0.1593) in cases of the brain, 0.4266 (SD: 0.1511) and 0.3666 (SD: 0.1533) in cases of the head and neck, and 1.0339 (SD: 0.5893) and 0.9498 (SD: 0.6047) in cases of the pelvis for the CBCT and OPI techniques, respectively. The P values were 0.3201, 0.0515, and 0.4829 for the brain, head and neck, and pelvic cases, respectively. CONCLUSIONS: There is statistically no significant difference between both the imaging techniques. As the dose delivered by the CBCT technique is higher than that by the OPI technique, from the socioeconomical and radiation safety point of view, the OPI technique is possibly better than the CBCT technique. Hence, it can be concluded that CBCT is not a mandatory technique compared to the OPI technique in routine brain, head and neck, and pelvic cases, except in those cases where better information about interfraction movements of soft tissue is necessarily required for positioning of the target, as is the case in prostate carcinoma.

Impact of repeat computerized tomography replans in the radiation therapy of head and neck cancers.

Anatomical changes can occur during course of head-and-neck (H and N) radiotherapy like tumor shrinkage, decreased edema and/or weight loss. This can lead to discrepancies in planned and delivered dose increasing the dose to organs at risk. A study was conducted to determine the volumetric and dosimetric changes with the help of repeat computed tomography (CT) and replanning for selected H and N cancer patients treated with IMRT plans to see for these effects. In 15 patients with primary H and N cancer, a repeat CT scan after 3(rd) week of radiotherapy was done when it was clinically indicated and then two plans were generated on repeat CT scan, actual plan (AP) planned on repeat CT scan, and hybrid plan (HP), which was generated by applying the first intensity-modulated radiation therapy (IMRT) plan (including monitoring units) to the images of second CT scan. Both plans (AP and HP) on repeat CT scan were compared for volumetric and dosimetric parameter. The mean variation in volumes between CT and repeat CT were 44.32 cc, 82.2 cc, and 149.83 cc for gross tumor volume (GTV), clinical target volumes (CTV), and planning target volume (PTV), respectively. Mean conformity index and homogeneity index was 0.68 and 1.07, respectively for AP and 0.5 and 1.16, respectively for HP. Mean D95 and D99 of PTV was 97.92% (standard deviation, SD 2.32) and 93.4% (SD 3.75), respectively for AP and 92.8% (SD 3.83) and 82.8% (SD 8.0), respectively for HP. Increase in mean doses to right parotid, left parotid, spine, and brainstem were 5.56 Gy (Dmean), 3.28 Gy (Dmean), 1.25 Gy (Dmax), and 3.88 Gy (Dmax), respectively in HP compared to AP. Repeat CT and replanning reduces the chance of discrepancies in delivered dose due to volume changes and also improves coverage to target volume and further reduces dose to organ at risk.

Radiation dose verification using real tissue phantom in modern radiotherapy techniques.

In vitro dosimetric verification prior to patient treatment has a key role in accurate and precision radiotherapy treatment delivery. Most of commercially available dosimetric phantoms have almost homogeneous density throughout their volume, while real interior of patient body has variable and varying densities inside. In this study an attempt has been made to verify the physical dosimetry in actual human body scenario by using goat head as "head phantom" and goat meat as "tissue phantom". The mean percentage variation between planned and measured doses was found to be 2.48 (standard deviation (SD): 0.74), 2.36 (SD: 0.77), 3.62 (SD: 1.05), and 3.31 (SD: 0.78) for three-dimensional conformal radiotherapy (3DCRT) (head phantom), intensity modulated radiotherapy (IMRT; head phantom), 3DCRT (tissue phantom), and IMRT (tissue phantom), respectively. Although percentage variations in case of head phantom were within tolerance limit (< ± 3%), but still it is higher than the results obtained by using commercially available phantoms. And the percentage variations in most of cases of tissue phantom were out of tolerance limit. On the basis of these preliminary results it is logical and rational to develop radiation dosimetry methods based on real human body and also to develop an artificial phantom which should truly represent the interior of human body.