The NUKDOS software for treatment planning in molecular radiotherapy

The aim of this work was the development of a software tool for treatment planning prior to molecular radiotherapy, which comprises all functionality to objectively determine the activity to administer and the pertaining absorbed doses (including the corresponding error) based on a series of gamma camera images and one SPECT/CT or probe data. NUKDOS was developed in MATLAB. The workflow is based on the MIRD formalismFor determination of the tissue or organ pharmacokinetics, gamma camera images as well as probe, urine, serum and blood activity data can be processed. To estimate the time-integrated activity coefficients (TIAC), sums of exponentials are fitted to the time activity data and integrated analytically. To obtain the TIAC on the voxel level, the voxel activity distribution from the quantitative 3D SPECT/CT (or PET/CT) is used for scaling and weighting the TIAC derived from the 2D organ data. The voxel S-values are automatically calculated based on the voxel-size of the image and the therapeutic nuclide (⁹⁰Y, ¹³¹I or ¹⁷⁷Lu). The absorbed dose coefficients are computed by convolution of the voxel TIAC and the voxel S-values. The activity to administer and the pertaining absorbed doses are determined by entering the absorbed dose for the organ at risk. The overall error of the calculated absorbed doses is determined by Gaussian error propagation.NUKDOS was tested for the operation systems Windows^® 7 (64 Bit) and 8 (64 Bit). The results of each working step were compared to commercially available (SAAMII, OLINDA/EXM) and in-house (UlmDOS) software. The application of the software is demonstrated using examples form peptide receptor radionuclide therapy (PRRT) and from radioiodine therapy of benign thyroid diseases. For the example from PRRT, the calculated activity to administer differed by 4% comparing NUKDOS and the final result using UlmDos, SAAMII and OLINDA/EXM sequentially. The absorbed dose for the spleen and tumour differed by 7% and 8%, respectively. The results from the example from radioiodine therapy of benign thyroid diseases and the example given in the latest corresponding SOP were identical. The implemented, objective methods facilitate accurate and reproducible results. The software is freely available.     

Comparative dosimetry of copper-64 and yttrium-90-labeled somatostatin analogs in a tumor-bearing rat model

90Y-DOTA-tyrosine3-octreotide (90Y-DOTA-Y3-OC) is currently being evaluated as a radiotherapy agent for trials in patients with somatostatin-receptor positive cancer. In this study, we compared the estimated absorbed doses to human organs, as well as to a CA20948 rat tumor, of 90Y- and 64Cu-labeled DOTA-Y3-OC and DOTA-Y3-octreotate (DOTA-Y3-TATE). Assuming that the radiopharmaceutical biodistributions are the same in rodents and humans, human absorbed dose estimates were obtained from rat biodistribution data. The absorbed doses of 90Y-DOTA-Y3-TATE were determined from the biodistribution of the 88Y-labeled peptide, with and without co-injection of a therapeutic amount of the 90Y-labeled peptide. Additionally, the absorbed doses of 90Y-DOTA-Y3-TATE were determined from data using two different biodistribution endpoints, 48 h and 168 h. Human absorbed dose estimates were calculated using MIRD methodology assuming that rats and humans have the same biodistribution. The biodistribution of the radiolabeled somatostatin analogs was dependent on the peptide and the radiometal. For 90Y-DOTA-Y3-TATE, the tumor dose was dependent on both the administration of therapeutic 90Y-peptide and the biodistribution endpoint. Our data suggested that, for both radionuclides, the TATE derivatives imparted a higher absorbed dose to the tumor than the OC analogs. 90Y-DOTA-Y3-OC and 64Cu-DOTA-Y3-OC were comparable with respect to their tumor-to-normal tissue dose ratios, while 90Y-DOTA-Y3-TATE appeared to have distinct advantages over 64Cu-DOTA-Y3-TATE.     

A Monte Carlo Program Converting Activity Distributions to Absorbed Dose Distributions in a Radionuclide Treatment Planning System

In systemic radiation therapy, the absorbed dose distribution must be calculated from the individual activity distribution. A computer code has been developed for the conversion of an arbitrary activity distribution to a 3-D absorbed dose distribution. The activity distribution can be described either analytically or as a voxel based distribution, which comes from a SPECT acquisition. Decay points are sampled according to the activity map, and particles (photons and electrons) from the decay are followed through the tissue until they either escape the patient or drop below a cut off energy. To verify the calculated results, the mathematically defined MIRD phantom and unity density spheres have been included in the code. Also other published dosimetry data were used for verification. Absorbed fractions and S-values were calculated. A comparison with simulated data from the code with MIRD data shows good agreement. The S values are within 10-20% of published MIRD S values for most organs. Absorbed fractions for photons and electrons in spheres (masses between 1 g and 200 kg) are within 10-15% of those published. Radial absorbed dose distributions in a necrotic tumor show good agreement with published data. The application of the code in a radionuclide therapy dose planning system, based on quantitative SPECT, is discussed     

Determination of individual S-values for 131I using segmented CT data and the EGS4 Monte Carlo code

In individual voxel phantoms, which were segmented from whole-body computed tomography (CT) scans, S-values were calculated for (131)I using the EGS4 Monte Carlo code and compared to Medical Internal Radiation Dose (MIRD) S-values, which were derived from transport calculations in idealized mathematical phantoms. The individually calculated S-values agree very well with the MIRD values for organs, which are source and target simultaneously, when individual organ-mass corrections are applied to the MIRD values. For different source-target combinations, large deviations up to 184% were found. The contribution of the gamma-absorbed fractions to the total dose, however, is small ( approximately 4%). We conclude, therefore, that individual transport calculations in radionuclide-targeted therapies are not necessary for macroscopic dose estimates. Reliable dosimetry is reduced to the problem of accurate activity determination in vivo.     

Internal dosimetry for systemic radiation therapy

The key to effective use of the medical internal radiation dose (MIRD) schema in radioimmunotherapy (RIT) is to understand how it works and what the essential data input requirements are. The fundamental data are acquired from medical imaging. Image interpretation involves (1) collecting data to determine the source-organ activities, (2) plotting the source-organ time-activity curves, (3) integrating the time-activity curves for an estimate of the residence time, and (4) applying the residence time values (for each important source organ) within the MIRD schema to calculate the tissue absorbed dose to target organs and tumors of interest. This article reviews methods for calculating internal dose. It also describes methods for selecting sampling times, integrating the area under the data curves, and customizing a dose assessment for a patient who does not resemble the MIRD phantom. A sample dose assessment is given, together with common mistakes to avoid. Three approaches to red marrow dosimetry are described. With the increased use of RIT agents for cancer treatment, a solid understanding of internal dose methods is essential for treatment planning and follow-up evaluations.     

Comparison between 2D and 3D dosimetry protocols in 90Y-ibritumomab tiuxetan radioimmunotherapy of patients with non-Hodgkin's lymphoma

We compared the radiation-absorbed dose obtained from a two dimensional (2D) protocol, based on planar whole-body (WB) scans and fixed reference organ masses with dose estimates, using a 3D single-photon emission computed tomography (SPECT) imaging protocol and patient-specific organ masses. METHODS: Six (6) patients with follicular non-Hodgkin's lymphoma underwent a computed tomography (CT) scan, 5 2D planar WB, and 5 SPECT scans between days 0 and 6 after the injection of (111)In-ibritumomab tiuxetan. The activity values in the liver, spleen, and kidneys were calculated from the 2D WB scans, and also from the 3D SPECT images reconstructed, using quantitative image processing. Absorbed doses after the administration of (90)Y-ibritumomab tiuxetan were calculated from the (111)In WB activity values combined with reference organ masses and also from the SPECT activity values and organ masses as estimated from the patient CT scan. To assess the quantitative accuracy of the WB and SPECT scans, an abdominal phantom was also studied. RESULTS: The differences between organ masses estimated from the patient CT and from the reference MIRD models were between -10% and +98%. Using the phantom, errors in organ and tumor activity estimates were between -86% and 10% for the WB protocol and between -43% and -6% for the SPECT protocol. Patient liver, spleen, and kidney activity values determined from SPECT were systematically less than those from the WB scans. Radiation-absorbed doses calculated with the 3D protocol were systematically lower than those calculated from the WB protocol (29%+/-26%, 73%+/-26%, and 33%+/-53% differences in the liver, spleen, and kidney, respectively), except in the kidneys of 2 patients and in the liver of 1 patient. CONCLUSIONS:Accounting for patient-specific organ mass and using SPECT activity quantification have both a great impact on estimated absorbed doses.     

Voxeldoes: a computer program for 3-D dose calculation in therapeutic nuclear medicine

A computer program, VoxelDose, was developed to calculate patient specific 3-D-dose maps at the voxel level. The 3-D dose map is derived in three steps: (i) The SPECT acquisitions are reconstructed using a filtered back projection method, with correction for attenuation and scatter; (ii) the 3-D cumulated activity map is generated by integrating the SPECT data; and (iii) a 3-D dose map is computed by convolution (using the Fourier Transform) of the cumulated activity map and corresponding MIRD voxel S values. To validate the VoxelDose software, a Liqui-Phil abdominal phantom with four simulated organ inserts and one spherical tumor (radius 4.2 cm) was filled with known activity concentrations of 111In. Four cylindrical calibration tubes (from 3.7 to 102 kBq/mL) were placed on the phantom. Thermoluminescent mini-dosimeters (mini-TLDs) were positioned on the surface of the organ inserts. Percent differences between the known and measured activity concentrations were determined to be 12.1 (tumor), 1.8 (spleen), 1.4, 8.1 (right and left kidneys), and 38.2% (liver), leading to percent differences between the calculated and TLD measured doses of 41, 16, 3, 5, and 62%. Large differences between the measured and calculated dose in the tumor and the liver may be attributed to several reasons, such as the difficulty in precisely associating the position of the TLD to a voxel and limits of the quantification method (mainly the scatter correction and partial volume effect). Further investigations should be performed to better understand the impact of each effect on the results and to improve absolute quantification. For all other organs, activity concentration measurements and dose calculations agree well with the known activity concentrations.     

Internal radionuclide dosimetry: diagnostic and therapeutic nuclear medicine,occupational and environmental exposures. Differences and similarities

In diagnostic nuclear medicine, model-derived effective dose estimates have been considered adequate for risk estimates for various patient groups. Average anthropomorphic models (normally MIRD models) and representative biokinetic models are used, with the main uncertainty being due to limited information on the biokinetics of the substance in representative groups of patients. In nuclear medicine therapy it is necessary to make patient-specific absorbed dose estimates, especially to dose-limiting risk organs and to the tumor tissue. Together with information on the time-activity curve (which may differ for the low test activity and the high therapeutic activity) in different organs and tissues, there is a need for detailed anatomical information, normally collected through CT- and/or MR-imaging through the body volumes of interest. The wish to get the radionuclide localized in the tumor cells and preferentially in the cell nuclei makes it essential to consider the increased biological effect resulting from the nonuniform distribution of the absorbed energy in tumors as well as in dose-limiting organs such as bone marrow, liver, and kidneys. The situation in occupational and environmental internal dosimetry resembles that of diagnostic nuclear medicine. However, biokinetic models derived for the former purposes are often constructed for relatively long-lived isotopes, and cannot be used for the short-lived isotopes of the same element, which are used in diagnostic nuclear medicine. Similarities and differences in objectives and methods for dosimetry in the different areas are discussed.     

A comparison of 131I-labeled monoclonal antibody 17-1A treatment to external beam irradiation on the growth of LS174T human colon carcinoma xenografts

Inhibition of growth of LS174T human colon cancer xenografts in athymic nude mice due to 131I-labeled MoAb 17-1A treatment was compared to inhibition due to different single doses of 60Co external radiation. From those data, conditions which produced equivalent radiobiological end points could be identified and compared to dose estimates calculated using a technique analogous to the Medical Internal Radiation Dose (MIRD) Committee formalism. The tumor growth rate in mice injected with a single intraperitoneal administration of 300 microCi of 131I-labeled MoAb was reduced relative to tumor growth in untreated control animals and in mice administered unlabeled MoAb and was found to be similar to the growth rate of tumors given a single 6 Gy dose of 60Co radiation. Furthermore, the growth rate of tumors in mice that received three injections of 300 microCi of 131I-labeled MoAb on days 9, 16 and 28 after tumor cell injection was similar to the growth rate of tumors given a single 60Co dose of 8 or 10 Gy. The biodistribution data for 125I-labeled 17-1A MoAb were used to calculate total doses for the tumor and various normal tissues in animals given a single administration of 131I-labeled 17-1A MoAb. The absorbed radiation dose in tumor was approximately five times higher than in normal tissues. The results of the present study indicate that the tumor growth inhibition produced by the administration of radiolabeled antibody can equal that produced by up to 10 Gy of external beam radiation. In addition, the MIRD calculations allow comparison of this form of low dose radiation to external photon irradiation.     

Comparison of radiation dose estimation for myeloablative radioimmunotherapy for relapsed or recurrent mantle cell lymphoma using (131)I tositumomab to that of other types of non-Hodgkin's lymphoma

Patients with relapsed or refractory mantle cell lymphoma (MCL) demonstrate poor survival after standard treatment. Myeloablative radioimmunotherapy (RIT) using (131)I tositumomab (anti-CD20) has the ability to deliver specific radiation-absorbed dose to antigen-bearing tumor. We reviewed normal organ radiation- absorbed doses in MCL patients. METHODS: Records of patients with MCL (n =25), who received myeloablative RIT between January 1996 and December 2003 were reviewed. Individual patient radiation dosimetry was performed on all patients after a trace-labeled infusion of (131)I tositumomab (mean = 348 MBq), to calculate the required amount of radioactivity for therapy, based on medical internal radiation dose (MIRD) schema. RESULTS: Mean organ residence times (hour) corrected for computed tomography (CT) derived organ volumes for MCL, were as follows: Lungs: 9.0; Liver: 12.4; Kidneys: 1.7; Spleen: 2.17; Whole Body: 62.4 and mean radiation absorbed doses mGy/Mbq were: Lungs: 1.2; Liver: 1.1; Kidneys: 0.85; Spleen: 1.7; Whole Body: 0.21. This is similar to patients with other non-Hodgkin's lymphoma (NHL). Patients received a mean activity of 21 GBq of (131)I (range, 11.5-41.4) for therapy estimated to deliver 25 Gy to the normal organ receiving the highest radiation-absorbed dose. CONCLUSION: Myeloablative RIT using (131)I tositumomab results in normal organ radiation-absorbed doses similar to those in patients with other non-Hodgkin's lymphoma, and is suitable for treating patients with relapsed or refractory MCL.     

99m Tc-HYNIC-TOC人体内照射剂量研究

背景与目的：放射性显像药物在人体内的剂量分布、各器官的吸收剂量及全身有效剂量数据非常重要。研究^99mTc标记的经肼基烟酰胺修饰的奥曲肽（^99mTc-Hydrazinonicotinyl-Tyr3-Octreotide,^99mTc-HYNIC-TOC）在人体内各器官的吸收剂量、全身吸收剂量及全身有效剂量。方法：对2018年5—6月复旦大学附属肿瘤医院收治的5例神经内分泌肿瘤患者静脉注射370 MBq^99mTc-HYNIC-TOC后于0.5、1.0、2.0、4.0和8.0 h行全身平面采集,其中2.0 h平面采集后即刻行全身断层采集。断层数据经迭代重建后,将数据导入GE Dosimetry Toolkit处理,在单光子发射计算机断层显像（single photon emission computedtomography,SPECT）/CT融合图像上勾画各器官生成感兴趣区（region of interest,ROI）,获得相应时间-活度曲线并计算曲线下面积得到滞留时间。依据美国核医学会医用内照射剂量学（Medical Internal Radiation Dose,MIRD）委员会提出的内照射剂量计算方法（MIRD体系）,利用OLINDA/EXM软件计算^99mTc-HYNIC-TOC在人体内各器官的吸收剂量、全身吸收剂量和全身有效剂量。结果：脾脏、膀胱、肾脏的单位活度吸收剂量较高,男性分别为0.042、0.019和0.016 mGy/MBq,女性分别为0.026、0.027和0.017 mGy/MBq。大脑、皮肤、甲状腺的单位活度吸收剂量较低,男性分别为0.000 3、0.000 5和0.000 5 mGy/MBq,女性分别为0.000 3、0.000 5和0.000 6 mGy/MBq。对放射线敏感的器官如骨原细胞、胸腺和红骨髓的单位活度吸收剂量均较低,范围为0.001 2~0.002 2 mGy/MBq。全身平均单位活度吸收剂量男性为0.001 7 mGy/MBq,女性为0.0016 mGy/MBq。全身单位活度有效剂量男性为0.004 58 mSv/MBq,女性为0.004 55 mSv/MBq。结论：^99mTc-HYNIC-TOC可安全地用于人体,其有效剂量低于允许范围上限。该研究结果可为临床安全使用^99mTc-HYNIC-TOC提供依据,也为其他放射性药物的安全性评估和加快临床转化提供新的可行方案。     

Application of MINERVA Monte Carlo simulations to targeted radionuclide therapy

Recent clinical results have demonstrated the promise of targeted radionuclide therapy for advanced cancer. As the success of this emerging form of radiation therapy grows, accurate treatment planning and radiation dose simulations are likely to become increasingly important. To address this need, we have initiated the development of a new, Monte Carlo transport-based treatment planning system for molecular targeted radiation therapy as part of the MINERVA system. The goal of the MINERVA dose calculation system is to provide 3-D Monte Carlo simulation-based dosimetry for radiation therapy, focusing on experimental and emerging applications. For molecular targeted radionuclide therapy applications, MINERVA calculates patient-specific radiation dose estimates using computed tomography to describe the patient anatomy, combined with a user-defined 3-D radiation source. This paper describes the validation of the 3-D Monte Carlo transport methods to be used in MINERVA for molecular targeted radionuclide dosimetry. It reports comparisons of MINERVA dose simulations with published absorbed fraction data for distributed, monoenergetic photon and electron sources, and for radioisotope photon emission. MINERVA simulations are generally within 2% of EGS4 results and 10% of MCNP results, but differ by up to 40% from the recommendations given in MIRD Pamphlets 3 and 8 for identical medium composition and density. For several representative source and target organs in the abdomen and thorax, specific absorbed fractions calculated with the MINERVA system are generally within 5% of those published in the revised MIRD Pamphlet 5 for 100 keV photons. However, results differ by up to 23% for the adrenal glands, the smallest of our target organs. Finally, we show examples of Monte Carlo simulations in a patient-like geometry for a source of uniform activity located in the kidney.     

Tumor dosimetry on SPECT (186)Re-HEDP scans: variations in the results from the reconstruction methods used

The aim of this work was to estimate tumor-absorbed doses delivered from the administration of fixed activities of (186)Re-HEDP for the treatment of bone metastases from prostate cancer. The variations and reproducibility in the estimated absorbed dose owing to the reconstruction algorithm used (OSEM vs. FBP) were also analysed. For this aim, correction methods for scatter and attenuation were kept identical, whereas the same calibration data and thresholding techniques were used to obtain quantification. This study was carried out in spinal and pelvic lesions of 7 patients. For comparison, the absorbed doses, based upon the maximum and the mean voxel count, were calculated, resulting in the absorbed dose (maximum): 60 Gy (sigma = 30 Gy) and 33 Gy (sigma = 15 Gy) for OSEM and FBP, respectively, and absorbed dose (mean): 26 Gy (sigma = 12 Gy) and 17 Gy (sigma = 7 Gy) with OSEM and FBP, respectively. We concluded that the administration of fixed activity resulted in a range of absorbed doses, and we showed that, despite using the same approach, the choice of the reconstruction algorithm can result in differences higher than 50% in the estimated tumor-absorbed doses. In conclusion, the need for a standardization of the methodology used for the calculations is emphasized by this work, especially when comparisons between patients and different centers are of interest.     

OEDIPE: a personalized dosimetric tool associating voxel-based models with MCNPX

AIM: A new tool, named OEDIPE (a French acronym that stands for "Tool for Personalized Internal Dose Assessment") was developed to carry out personalized internal dosimetry calculations for nuclear medicine (for both therapeutic and diagnostic procedures) and for radiation safety (in the case of internal contamination). It was developed under the PV-Wave visual data analysis system by the Institute of Radioprotection and Nuclear Safety (IRSN) in collaboration with the French Institute of Health and Medical Research (INSERM). This software creates anthropomorphic voxel-based phantoms from computed tomography (CT) and magnetic resonance imaging (MRI) patient images through the use of a friendly graphical user interface (GUI). Several tools have been built-in to allow for image segmentation. Source data, including VOI localization and cumulated activities, are assessed by single photon emission computed tomography (SPECT) images, and the source may be specified in any number of organs either as a point source or a homogeneously distributed source. It is also possible to choose the dosimetric parameters required for the study (mean organ dose or a dose distribution). Phantom, source, and dosimetric parameters are automatically written into a file. That file is then processed by the Monte Carlo code MCNPX (LANL) to perform the actual dose calculation. RESULTS: OEDIPE can compute either the absorbed dose in each organ (in a few minutes), or the absorbed dose in each voxel of the phantom (i.e. the spatial dose distribution at a tissue level) in a few hours or more. OEDIPE automatically reads the MCNPX output file and processes results to give a list of absorbed doses in each organ or a plot of isodose curves superimposed onto the phantom. Because of the long calculation times required to compute an absorbed dose within an entire whole-body phantom at a spatial resolution of a few millimeters, modifications were made to reduce computational times to reasonable values. To illustrate this tool, results of a dosimetric study of technetium-99m labeling of a bone-scanning agent are presented. CONCLUSION: OEDIPE is a tool that can be used for patient-specific dosimetry--for example, in targeted radiotherapy--by taking into account the individual patient anatomy, including tumors.     

Voxel-S-value methods adapted to heterogeneous media for quantitative Y-90 microsphere radioembolization dosimetry

PurposeThe absorbed dose estimation from Voxel-S-Value (VSV) method in heterogeneous media is suboptimal as VSVs are calculated in homogeneous media. The aim of this study is to develop and evaluate new VSV methods in order to enhance the accuracy of Y-90 microspheres absorbed dose estimation in liver, lungs, tumors and lung-liver interface regions.MethodsTen patients with Y-90 microspheres SPECT/CT and PET/CT data, six of whom had additional Tc-99m-macroaggregated albumin SPECT/CT data, were analyzed from the Deep Blue Data Repository. Seven existing VSV methods along with three newly proposed VSV methods were evaluated: liver and lung kernel with center voxel scaling (LiLuCK), liver kernel with density correction and lung kernel with center voxel scaling (LiKDLuCK), liver kernel with center voxel scaling and lung kernel with density correction (LiCKLuKD). Monte Carlo (MC) results were regarded as the gold standard. Absolute absorbed dose errors (%AADE) of these methods for the liver, lungs, tumors, upper liver, and lower lungs were assessed.ResultsLiver and tumor’s median %AADE of all methods were <3% for three types of imaging data. In the lungs, however, three recently proposed VSV methods provided median %AADEs of less than 7%, whereas the differences exceeded 20% for existing methods that did not use a lung kernel. LiCKLuKD could achieve median %AADE <2% in the liver, upper liver and tumors, and median %AADE <7% in the lungs and lower lungs in three types of data.ConclusionAll methods are consistent with MC in the liver and tumors. Methods with tissue-specific kernel and effective correction achieve smaller errors in lungs. LiCKLuKD has comparable results with MC in absorbed dose estimation of Y-90 radioembolization for all target regions.     

Comparison of different thyroid committed doses in radioiodine therapy for Graves' hyperthyroidism

Despite vast worldwide experience in the use of 131I for treating Graves' disease (GD), no consensus of opinion exists concerning the optimal method of dose calculation. In one of the most popular equations, the administered (131)I dose is directly proportional to the estimated thyroid gland volume and inversely proportional to the measured 24-hour radioiodine uptake. In this study, we compared the efficiency of different tissue-absorbed doses to induce euthyroidism or hypothyroidism within 1 year after radioiodine therapy in GD patients. The study was carried out in 134 GD patients (age, 53 +/- 14 year; range, 16-82 year; thyroid volume, 28 +/- 18 mL; range, 6-95 mL; average 24-hour thyroid uptake, 72%) treated with (131)I therapy. The average radioiodine activity administered to patients was 518 +/- 226 MBq (range, 111-1110). The corresponding average thyroid absorbed dose, calculated by a modified Medical Internal Radiation Dose (MIRD) equation was 376 +/- 258 Gy (range, 99-1683). One year after treatment, 58 patients (43%) were hypothyroid, 57 patients (43%) were euthyroid, and 19 patients (14%) remained hyperthyroid. The patients were divided into 3 groups: 150 Gy (n = 32), 300 Gy (n = 58) and >300 Gy (n = 44). No significant difference in the rate of recurrent hyperthyroidism was found among the 3 groups (150 Gy: 15%; 300 Gy: 14%; and > or =300 Gy: 14%; chi-square test, p = 0.72). Whereas, the rate of hypothyroidism in the 3 groups was significantly correlated with the dose (150 Gy: 30%; 300 Gy: 46%; >300 Gy: 71%; chi-square test, p = 0.0003). The results obtained in this study show no correlation between dose and outcome of radioiodine therapy (in terms of persistent hyperthyroidism) for thyroid absorbed doses > or =150 Gy, while confirming the relation between the thyroid absorbed dose and the incidence of hypothyroidism in GD patients.     

The use of TL detectors in dosimetry of systemic radiation therapy

A method for determining absorbed doses to organs in systemic radiation therapy (SRT) is evaluated. The method, based on thermoluminescent (TL) dosimeters placed on the patient's skin, was validated and justified through a phantom study showing that the difference between measured (TL dosimeters in the phantom) and derived (TL method) values is within 10%. Six radioimmunotherapy (RIT) patients with widespread intraperitoneal pseudomyxoma were also studied. In dose evaluations, special emphasis was on kidneys. In addition to the TL method, the absorbed doses to kidneys were calculated using MIRD formalism and a point dose kernel technique. We conclude that in SRT the described TL method can be used to estimate the absorbed doses to those critical organs near the body surface within 50% (1 SD).     

A quality-control method for SPECT-based dosimetry in targeted radionuclide therapy

Dosimetry for targeted radionuclide therapy is necessary for treatment planning and radiation protection. Currently, there are no standard methods either for performing dosimetry or to evaluate the uncertainties inherent in the dosimetric calculations. In this paper, we present an experimental method using polymer gel dosimeters, whereby absorbed-dose distributions resulting from nonuniform distributions of activity may be determined directly from T(2) magnetic resonance imaging (MRI) as well as from scintigraphic images. A phantom containing a nonuniform distribution of I-131 was prepared by mixing 58 MBq of activity within the gel as it was solidifying. The resulting absorbed-dose distribution was determined directly from the MRI and from sequential single-photon emission computed tomography (SPECT) images using the Medical Internal Radiation Dose (MIRD) schema. The MRI data were quantified using 12 calibration vials uniformly irradiated by 0-12 MBq of I-131. The agreement between the two absorbed-dose maps was verified by convolving the MRI-based absorbed-dose map with the SPECT system point spread function, which gave a correlation coefficient of 0.96. It was seen that the absorbed-dose distribution, as imaged by the MRI, was misrepresented by the SPECT owing to its relatively poor spatial resolution, which included a shift of the voxel containing the maximum absorbed dose. This technique could provide an independent benchmark for assessing patient-specific dosimetry and, therefore, could be used as a basis for quality control for dosimetry.     

4D Proton treatment planning strategy for mobile lung tumors

PURPOSE: To investigate strategies for designing compensator-based 3D proton treatment plans for mobile lung tumors using four-dimensional computed tomography (4DCT) images. METHODS AND MATERIALS: Four-dimensional CT sets for 10 lung cancer patients were used in this study. The internal gross tumor volume (IGTV) was obtained by combining the tumor volumes at different phases of the respiratory cycle. For each patient, we evaluated four planning strategies based on the following dose calculations: (1) the average (AVE) CT; (2) the free-breathing (FB) CT; (3) the maximum intensity projection (MIP) CT; and (4) the AVE CT in which the CT voxel values inside the IGTV were replaced by a constant density (AVE_RIGTV). For each strategy, the resulting cumulative dose distribution in a respiratory cycle was determined using a deformable image registration method. RESULTS: There were dosimetric differences between the apparent dose distribution, calculated on a single CT dataset, and the motion-corrected 4D dose distribution, calculated by combining dose distributions delivered to each phase of the 4DCT. The AVE_RIGTV plan using a 1-cm smearing parameter had the best overall target coverage and critical structure sparing. The MIP plan approach resulted in an unnecessarily large treatment volume. The AVE and FB plans using 1-cm smearing did not provide adequate 4D target coverage in all patients. By using a larger smearing value, adequate 4D target coverage could be achieved; however, critical organ doses were increased. CONCLUSION: The AVE_RIGTV approach is an effective strategy for designing proton treatment plans for mobile lung tumors.