Radiobiological Dosimetry Research Articles

Ocular malignancies treated with iodine-125 low dose rate (LDR) brachytherapy at a single high-volume institution: A retrospective review.

The aim of our study is to document our cases of choroidal melanoma treated with low dose rate (LDR) brachytherapy and to correlate the dosimetry and radiobiology with clinical effects and oncologic outcomes. Data from 157 patients treated from 2014 to 2018 with LDR brachytherapy were used for this investigation. Treatments used a collaborative ocular melanoma study eye plaque and Iodine-125 radioactive seeds. The seeds activities were chosen to deliver 85 Gy to the tumor apex or to a prescription point (if the apex < 5 mm). The plaque sizes used were 10, 12, 14, 16, 18, 20, and 22 mm including notched or deep notched. The plaques were modeled in Varian BrachyVision version 11.6 (Varian Medical Systems) with seed coordinates from the AAPM Task Group 129. The Task Group 43 from AAPM was used for brachytherapy dose planning. Dose data were extracted for the apex, prescription point, sclera, retina opposite to the implant, lens, macula, and optic disc. The radiobiological dosimetry were calculated using appropriate α/β ratios found in the literature and then correlated to clinical side effects. Average biologically effective dose for associated organs at risk were calculated in cases where toxicity occurred. These included: radiation cataract (70.66 Gy), disc atrophy (475.49 Gy), foveal atrophy (263.07 Gy), radiation papillopathy (373.45 Gy), radiation maculopathy (213.62 Gy), vitreous hemorrhage (1437.68 Gy), vascular occlusion (1080.93 Gy), nonproliferative retinopathy (1066.89 Gy), proliferative retinopathy (1590.71 Gy), exudative retinal detachment (1364.32 Gy), and rhegmatogenous retinal detachment (2265.54 Gy). Average biologically effective dose was higher in patients who developed radiation induced long term side effects than in the whole patient population except for radiation maculopathy. In spite of the small patient population and short-term follow-up, it is of interest to correlate the radiation induced effects and create a guideline for the improvement of the treatment of patients treated with LDR brachytherapy.

Improved FBX chemical dosimeter system with enhanced radiochemical yield for reference dosimetry in radiobiology and radiotherapy research

Radiation dosimetry plays important role in the reproducibility of radiobiology experiments, in the replicability of results, as well as in the successful and safe use of radiotherapy procedures. The consistency and accuracy of the applied dosimetry methods pre-define the outcomes of these applications. This paper presents a version of the well-known ferrous sulphate – benzoic acid – xylenol orange (FBX) chemical dosimeter with improved sensitivity, accuracy and precision. Sensitivity is increased due to a slight modification in composition and the preparation procedures. We use stock solutions for the preparation of the dosimeter solution, which consists of 1 mM ferrous sulphate and 16 mM benzoic acid with 0.25 mM xylenol orange added post-irradiation. The nonlinear response to the absorbed dose of this system is eliminated by the increased ferrous sulphate concentration, permitting the calculation of the absorbed dose by a linear relationship between the absorbed dose and the optical absorbance of the solution. The measured chemical yield of our dosimeter is 9.08⋅10−6mol/J for 6 MV photon beams and 6.42⋅10−6mol/J for 250 kVp x-rays. This is a 24% enhancement over the original FBX solution, which permits a finer dose resolution. The accuracy and precision of our method is assured by a well-designed and consistently used practice. A custom designed multipurpose PMMA slab phantom was used for irradiation in reference conditions. This phantom can be used for irradiation in reference conditions of dosimetric solutions, dosimetric films and chemical or biological samples. The combined standard uncertainty of this system is 1.12%, which can be improved by using an appropriate temperature correction factor. Furthermore, a working protocol has been established which allows dosimetry measurements using less than 1 mL dosimetric solutions.

IRIDIUM-192 RADIOTHERAPY BENEFITS IN THE MANAGEMENT OF GYNECOLOGICAL TUMORS.

Application of the most advanced radiation technologies of brachytherapy featuring the high dose ratesources i.e. 60Co and 192Ir within contemporary management protocols for gynecological cancer provides maximum dosedistribution in the clinical target along with minimal radiation exposure on surrounding organs and tissues. It involvesirradiation of large spaces with delivery of high therapeutic doses at the tolerance bound of «critical» organs (bladder,rectum) and tissues. Thus minimization of the early and late radiation complications, life span extent and quality oflife increase remain just the issues in contemporary radiation oncology requiring therefore the elaboration of radiobiological criteria along with substantiation of physiсо-engineering properties of the radiation sources. Taking intoaccount the basic radiobiological patterns will ensure a definitive further progress in the field of radiation oncology. to study and compare the biological effects of 192Ir with the effects of the reference gamma radiation 60Coand increase the effectiveness of brachytherapy using a 192Ir source. Radiobiological dosimetry on the basis of a test system of peripheral blood lymphocytesfrom the gynecological cancer patients with subsequent cytogenetic analysis of radiation-induced chromosomeaberrations was performed to study and compare the biological effects of 192Ir and reference 60Со γ-radiation, and toenhance the efficiency of 192Ir brachytherapy. Radiation markers, i.e. dicentric chromosomes with an accompanying paired fragment prevailed in thespectrum of radiation-induced damage. Variability of individual cytogenetic parameters of peripheral lymphocytesupon the first fraction of irradiation at the same dose of 5 Gy indicated an individual sensitivity of patients to the192Ir γ-irradiation. Comprehensive conservative treatment with adjuvant radiotherapy was applied to the patients(n = 98) having got secondary vaginal cancer stage II-III, T2-3N0-1M0. The high dose-rate (HDR) brachytherapy using 192Ir radiation sources was applied in the main study group (n = 37), HDR brachytherapy using 60Co radiation sourceswas applied in the control group (n = 35). The HDR brachytherapy with 192Ir and 60Co sources on the up-to-date technology intensive devices provides a high accuracy of dose distributions when irradiating the malignant neoplasms with minimized radiationexposure to the «critical» tissues. Treatment results are improved therefore. The use of 192Ir radiation sources compared with 60Co ones resulted in an increased throughput of treatment, enhanced tumor regression, and reduced incidence of radiation effects on the critical organs. Currently we perform the radiobiological studies on somatic cellsfrom cancer patients at the genetic, biochemical, biophysical, and cytological levels in order to receive a biologicalindication of radiation damage under the impact of 192Ir isotope. Continuation of clinical trials with radiobiologicalsupport will provide an opportunity to predict the early and late radiation complications and thus to provide a personalized approach in brachytherapy of cancer patients using the 192Ir sources of γ-rays.

Tumor and red bone marrow dosimetry: comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy.

BackgroundRed bone marrow (RBM) toxicity is dose-limiting in (pretargeted) radioimmunotherapy (RIT). Previous blood-based and two-dimensional (2D) image-based methods have failed to show a clear dose-response relationship. We developed a three-dimensional (3D) image-based RBM dosimetry approach using the Monte Carlo-based 3D radiobiological dosimetry (3D-RD) software and determined its additional value for predicting RBM toxicity.MethodsRBM doses were calculated for 13 colorectal cancer patients after pretargeted RIT with the two-step administration of an anti-CEA × anti-HSG bispecific monoclonal antibody and a 177Lu-labeled di-HSG-peptide. 3D-RD RBM dosimetry was based on the lumbar vertebrae, delineated on single photon emission computed tomography (SPECT) scans acquired directly, 3, 24, and 72 h after 177Lu administration. RBM doses were correlated to hematologic effects, according to NCI-CTC v3 and compared with conventional 2D cranium-based and blood-based dosimetry results. Tumor doses were calculated with 3D-RD, which has not been possible with 2D dosimetry. Tumor-to-RBM dose ratios were calculated and compared for 177Lu-based pretargeted RIT and simulated pretargeted RIT with 90Y.Results3D-RD RBM doses of all seven patients who developed thrombocytopenia were higher (range 0.43 to 0.97 Gy) than that of the six patients without thrombocytopenia (range 0.12 to 0.39 Gy), except in one patient (0.47 Gy) without thrombocytopenia but with grade 2 leucopenia. Blood and 2D image-based RBM doses for patients with grade 1 to 2 thrombocytopenia were in the same range as in patients without thrombocytopenia (0.14 to 0.29 and 0.11 to 0.26 Gy, respectively). Blood-based RBM doses for two grade 3 to 4 patients were higher (0.66 and 0.51 Gy, respectively) than the others, and the cranium-based dose of only the grade 4 patient was higher (0.34 Gy). Tumor-to-RBM dose ratios would increase by 25% on average when treating with 90Y instead of 177Lu.Conclusions3D dosimetry identifies patients at risk of developing any grade of RBM toxicity more accurately than blood- or 2D image-based methods. It has the added value to enable calculation of tumor-to-RBM dose ratios.

Three‐dimensional radiobiological dosimetry of kidneys for treatment planning in peptide receptor radionuclide therapy

Peptide receptor radionuclide therapy (PRRT) delivers high absorbed doses to kidneys and may lead to permanent nephropathy. Reliable dosimetry of kidneys is thus critical for safe and effective PRRT. The aim of this work was to assess the feasibility of planning PRRT based on 3D radiobiological dosimetry (3D-RD) in order to optimize both the amount of activity to administer and the fractionation scheme, while limiting the absorbed dose and the biological effective dose (BED) to the renal cortex. Planar and SPECT data were available for a patient examined with (111)In-DTPA-octreotide at 0.5 (planar only), 4, 24, and 48 h post-injection. Absorbed dose and BED distributions were calculated for common therapeutic radionuclides, i.e., (111)In, (90)Y and (177)Lu, using the 3D-RD methodology. Dose-volume histograms were computed and mean absorbed doses to kidneys, renal cortices, and medullae were compared with results obtained using the MIRD schema (S-values) with the multiregion kidney dosimetry model. Two different treatment planning approaches based on (1) the fixed absorbed dose to the cortex and (2) the fixed BED to the cortex were then considered to optimize the activity to administer by varying the number of fractions. Mean absorbed doses calculated with 3D-RD were in good agreement with those obtained with S-value-based SPECT dosimetry for (90)Y and (177)Lu. Nevertheless, for (111)In, differences of 14% and 22% were found for the whole kidneys and the cortex, respectively. Moreover, the authors found that planar-based dosimetry systematically underestimates the absorbed dose in comparison with SPECT-based methods, up to 32%. Regarding the 3D-RD-based treatment planning using a fixed BED constraint to the renal cortex, the optimal number of fractions was found to be 3 or 4, depending on the radionuclide administered and the value of the fixed BED. Cumulative activities obtained using the proposed simulated treatment planning are compatible with real activities administered to patients in PRRT. The 3D-RD treatment planning approach based on the fixed BED was found to be the method of choice for clinical implementation in PRRT by providing realistic activity to administer and number of cycles. While dividing the activity in several cycles is important to reduce renal toxicity, the clinical outcome of fractionated PRRT should be investigated in the future.

Three-dimensional radiobiological dosimetry (3D-RD) with 124I PET for 131I therapy of thyroid cancer

Radioiodine therapy of thyroid cancer was the first and remains among the most successful radiopharmaceutical (RPT) treatments of cancer although its clinical use is based on imprecise dosimetry. The positron emitting radioiodine, (124)I, in combination with positron emission tomography (PET)/CT has made it possible to measure the spatial distribution of radioiodine in tumors and normal organs at high resolution and sensitivity. The CT component of PET/CT has made it simpler to match the activity distribution to the corresponding anatomy. These developments have facilitated patient-specific dosimetry (PSD), utilizing software packages such as three-dimensional radiobiological dosimetry (3D-RD), which can account for individual patient differences in pharmacokinetics and anatomy. We highlight specific examples of such calculations and discuss the potential impact of (124)I PET/CT on thyroid cancer therapy.

Fourier Transform Infrared Microspectroscopy and Multivariate Methods for Radiobiological Dosimetry

The scientific literature contains an ever-growing number of reports of applications of vibrational spectroscopy as a multivariate non-invasive tool for analysis of biological effects at the molecular level. Recently, Fourier transform infrared microspectroscopy (FTIRM) has been demonstrated to be sensitive to molecular events occurring in cells and tissue after exposure to ionizing radiation. In this work the application of FTIRM in the examination of dose-dependent molecular effects occurring in skin cells after exposure to ionizing radiation with the use of partial least-squares regression (PLSR) and generalized regression neural networks (GRNN) was studied. The methodology is shown to be sensitive to molecular events occurring with radiation dose and time after exposure. The variation in molecular species with dose and time after irradiation is shown to be non-linear by virtue of the higher modeling efficiency yielded from the non-linear algorithms. Dose prediction efficiencies of approximately +/-10 mGy were achieved at 96 h after irradiation, highlighting the potential applications of the methodology in radiobiological dosimetry.

Biological dose volume histograms during conformal hypofractionated accelerated radiotherapy for prostate cancer

Radiobiological data suggest that prostate cancer has a low alpha/beta ratio. Large radiotherapy fractions may, therefore, prove more efficacious than standard radiotherapy, while radiotherapy acceleration should further improve control rates. This study describes the radiobiology of a conformal hypofractionated accelerated radiotherapy scheme for the treatment of high risk prostate cancer. Anteroposterior fields to the pelvis deliver a daily dose of 2.7 Gy, while lateral fields confined to the prostate and seminal vesicles deliver an additional daily dose of 0.7 Gy. Radiotherapy is accomplished within 19 days (15 fractions). Dose volume histograms, calculated for tissue specific alpha/beta ratios and time factors, predict a high biological dose to the prostate and seminal vesicles (77-93 Gy). The biological dose to normal pelvic tissues is maintained at standard levels. Radiobiological dosimetry suggests that, using hypofractionated and accelerated radiotherapy, high biological radiation dose can be given to the prostate without overdosing normal tissues.

Characterization of neutron beams for boron neutron capture therapy: in-air radiobiological dosimetry.

The survival curves and the RBE for the dose components generated in boron neutron capture therapy (BNCT) were determined separately in neutron beams at Japan Research Reactor No. 4. The surviving fractions of V79 Chinese hamster cells with or without 10B were obtained using an epithermal neutron beam (ENB), a mixed thermal-epithermal neutron beam (TNB-1), and a thermal (TNB-2) neutron beam; these beams were used or are planned for use in BNCT clinical trials. The cell killing effect of the neutron beam in the presence or absence of 10B was highly dependent on the neutron beam used and depended on the epithermal and fast-neutron content of the beam. The RBEs of the boron capture reaction for ENB, TNB-1 and TNB-2 were 4.07 +/- 0.22, 2.98 +/- 0.16 and 1.42 +/- 0.07, respectively. The RBEs of the high-LET dose components based on the hydrogen recoils and the nitrogen capture reaction were 2.50 +/- 0.32, 2.34 +/- 0.30 and 2.17 +/- 0.28 for ENB, TNB-1 and TNB-2, respectively. The RBEs of the neutron and photon components were 1.22 +/- 0.16, 1.23 +/- 0.16, and 1.21 +/- 0.16 for ENB, TNB-1 and TNB-2, respectively. The approach to the experimental determination of RBEs outlined in this paper allows the RBE-weighted dose calculation for each dose component of the neutron beams and contributes to an accurate inter-beam comparison of the neutron beams at the different facilities employed in ongoing and planned BNCT clinical trials.

Protocol for X-ray dosimetry in radiobiology

Purpose : To harmonize X-ray dosimetry in radiobiology to allow a direct comparison of radiobiological studies performed at institutes cooperating within the framework of the European Late Effects Project Group (EULEP). Materials and methods : The 1985 EULEP protocol for X-ray dosimetry and exposure arrangements employed for studies of late somatic effects in mammals required serious revision, e.g. due to the replacement of calibration of dosemeters in terms of exposure by calibration in terms of air kerma free-in-air. An action group established by EULEP and the European Radiation Dosimetry Group (EURADOS) updated the 1985 protocol. Results : The new EULEP-EURADOS protocol for X-ray dosimetry in radiobiology including the code of practice for irradiation of small animals and related dosimetry. The present protocol includes the changes in calibration procedures and dosimetric concepts for irradiation with medium energy X-rays since 1985. Accuracy and precision are replaced by the concept of combined (standard) uncertainty. The revised supplements provide more detailed background information. New appendices contain definitions of general terms used for measurements and mathematical expressions of the relative variances. Conclusion : Adherence to the present protocol will result in improved dosimetry and facilitates the comparison of results of radiobiological experiments obtained at different institutes.

Fast-FISH technique for rapid, simultaneous labeling of all human centromeres

Fluorescence in situ hybridization (FISH) has become a powerful tool in chromosome analysis. This report describes the systematic optimization of the Fast-FISH technique for centromere labeling of human metaphase chromosomes for radiobiological dosimetry purposes. For the present study, the hybridization conditions and the efficiency of two commercially available alpha-satellite DNA probes were compared ("human chromosome 1 specific", Oncor, Gaithersburg, MD, vs. "all-human chromosomes specific", Boehringer-Mannheim, Germany). These probes were hybridized to human lymphocyte metaphase plates by using a hybridization buffer without formamide and without any other equivalent denaturing chemical agents. The results indicate the suitability of the method for automated image analysis on the basis of thresholding. The optimal conditions concerning hybridization time and temperature were determined by a systematic quantitative evaluation of the fluorescent labeling sites after the hybridization procedures. Under defined "low stringency" conditions, we found that the "human chromosome 1 specific" DNA probe labeled not only the centromere of the human chromosome 1 but also the other human centromeres in the same way as the "all-human chromosome specific" DNA probe. The optimized conditions to complete all centromere labeling were applied to the detection of dicentric chromosomes on irradiated human lymphocyte samples (gamma-rays of 60Co source, 0.5 Gy/min, for doses of 1, 3, and 4 Gy). The yield of dicentrics was determined after Fast-FISH and compared with results obtained after Giemsa staining. These results are very compatible and indicate that, because of its simplicity, this optimized Fast-FISH procedure would be useful for fast screening purposes in biological dosimetry after accidental overexposure.

Recent EULEP dosimetry intercomparisons for whole body irradiation of mice

. Purpose: To foster quality assurance of dosimetry among the institutes involved in joint studies on late effects of ionizing radiation. Materials and methods: The participants in the dosimetry intercomparison received for each facility two mouse phantoms loaded with LiF thermoluminescent dosemeters (TLD) and a control badge. The participants were requested to irradiate the test phantoms in the actual arrangement used for whole body irradiation of mice, such that the dose in the centre of the test phantoms was 2 Gy and the dose distribution was uniform. The readout of the TLD and the dose evaluation were made at the organizing institute. Results: Ten institutes operating 14 exposure facilities in four countries took part in the intercomparison. For one facility a dose deviation between 5 and 10% was found, whereas for two others the deviation exceeded 10%. The requirement for uniform dose distribution in a mouse phantom was not fulfilled by six exposure facilities. The causes for the dose discrepancies were found for two participants whereas for one participant the problems were only partly resolved. Non-uniform dose distributions are mainly related to unilateral irradiations. Conclusion: The seven EULEP dosimetry intercomparisons clearly show the need for quality assurance of dosimetry in radiobiology.

Cytogenetic study in lymphocytes from children exposed to ionizing radiation after the Chernobyl accident

The present study concerns the monitoring of children from the Byelorussian, Ukrainian and Russian republics exposed to the fall-out of the Chernobyl accident. Cytogenetic analyses have been performed on 41 children coming from different areas and exhibiting varying amounts of 137Cs internal contamination, as evaluated by whole-body counter (WBC) analysis. On a total of 28670 metaphases scored, radiation-induced chromosome damage is still present, although at a very low frequency. Due to the very low fraction of dicentrics, because of the time elapsed from the accident and the relatively low doses of exposure, radiobiological dosimetry is not possible for these children. However, considering that the WBC data indicate that the children are still exposed to 137Cs contamination, the observed occurrence of stable chromosome rearrangements and breaks may represent the persisting effect of continuous low doses of radiation. The present study also indicates that the parallel use of internal contamination dosimetry and cytogenetics could be usefully employed to monitor individual exposure to radiation and to define further management measures.

Application of the linear-quadratic model with incomplete repair to radionuclide directed therapy

The linear-quadratic (LQ) model for fractionated external beam therapy has been modified by previous authors to include the effects due to an exponentially decaying dose rate. However, the LQ model has now been extended to include a general time varying dose rate profile, and the equations can be readily evaluated if an exponential radiation damage repair process is assumed. These equations are applicable to radionuclide directed therapy, including brachytherapy. Kinetic uptake data obtained during radionuclide directed therapy may therefore be used to determine the radiobiological dosimetry of the target and non-target tissues. Also, preliminary tracer studies may be used to pre-plan the radionuclide directed therapy, provided that tracer and therapeutic amounts of the radionuclide carrier are identically processed by the tissues. It is also shown that continuous radionuclide therapy will induce less damage in late-responding tissues than 2 Gy/fraction external beam therapy if the ratio of the maximum dose rate and the sublethal damage repair half-life in the tissue is less than 1.0 Gy. Similar inequalities may be derived for beta-particle radionuclide directed therapy. For example, it can be shown that radionuclide directed therapy will induce less damage to slowly repopulating tissue than 2 Gy/fraction external beam therapy for the same total dose if the maximum percentage initial uptake in tissue is less than 0.046%/g or 0.23%/g for an injected activity of 50 mCi of 90Y or 131I, respectively.

Sensitivity enhancement effects in the thermoluminescence of LiF TLD-100 at radiation doses below 10 Gy

LiF TLD-100 ribbons are frequently used for a wide range of radiobiological dosimetry applications using various sources in the dose range 0.1-10 Gy. It is suggested that an accuracy of 5-6% and a precision of 2-3% is required for the determination of absorbed dose in biological applications. To minimise the random errors, the dosemeters are calibrated individually. The authors examine the systematic errors that may be introduced by this procedure. They have observed, for instance, that the calibration procedure itself enhances the sensitivity of the dosemeters by 1-2% and that this enhancement is dependent upon their thermal history. They describe the procedures that have been established at the Gray Laboratory for routine precision thermoluminescence dosimetry. Particular attention is given to the sensitivity correction factor that is necessary to allow for enhancement effects due to supralinearity and the dosemeter thermal history.

Quantitative Concepts and Dosimetry in Radiobiology

Medical PhysicsVolume 7, Issue 5 p. 577-578 Quantitative Concepts and Dosimetry in Radiobiology S. Julian Gibbs, S. Julian Gibbs ReviewerSearch for more papers by this author S. Julian Gibbs, S. Julian Gibbs ReviewerSearch for more papers by this author First published: September 1980 https://doi.org/10.1118/1.594757AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume7, Issue5September 1980Pages 577-578 RelatedInformation

Quantitative Concepts and Dosimetry in Radiobiology

Quantitative Concepts and Dosimetry in Radiobiology

Quantitative Concepts and Dosimetry in Radiobiology

Quantitative Concepts and Dosimetry in Radiobiology

Mean skeletal dose factors for beta-particle emitters in human bone. Part I: volume-seeking radionuclides.

Based on calculations by Whitwell and Spiers, mean skeletal dose factors for beta-particle emitters have been derived for application to dosimetry in nuclear medicine, radiobiology and radiation protection. The dose factors apply to bone-seeking radionuclides that are depostited more or less uniformly throughout the human mineralized skeleton and are defined as: (1) vDM/DB, the mean dose to the haemopoietic marrow in trabecular bone as a fraction of the "dose to bone", DB; (2) vDs/DB, the mean dose to endosteal (osteogenic) tissue lying in a zone 0--10 micron from trabecular surfaces, also as a fraction of the dose DB. Dose factors are given for three ages, 1.7, 9 and 44 years and for eight radionuclides, ranging in mean beta-particle energy from 0.05 MeV (14C) to 0.93 MeV (90Y). Dose factors, calculated for a single lumbar vertebra of an infant aged 3.5 weeks, enable approximate values of mean skeletal dose factors to be estimated for ages less than 1.7 years. Limited data are also reported on dose factors for the femoral cortex from subjects aged 9 and 50 years.

Experience in radiobiological dosimetry with high-dose-rate electrons.

Experience in radiobiological dosimetry with high-dose-rate electrons.