Radiopharmaceutical Dosimetry Research Articles

3D small-scale dosimetry and tumor control of 225Ac radiopharmaceuticals for prostate cancer

Radiopharmaceutical therapy using α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upalpha$$\\end{document}-emitting 225\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{225}$$\\end{document}Ac is an emerging treatment for patients with advanced metastatic cancers. Measurement of the spatial dose distribution in organs and tumors is needed to inform treatment dose prescription and reduce off-target toxicity, at not only organ but also sub-organ scales. Digital autoradiography with α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upalpha$$\\end{document}-sensitive detection devices can measure radioactivity distributions at 20–40 μm\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upmu {\\hbox {m}}$$\\end{document} resolution, but anatomical characterization is typically limited to 2D. We collected digital autoradiographs across whole tissues to generate 3D dose volumes and used them to evaluate the simultaneous tumor control and regional kidney dosimetry of a novel therapeutic radiopharmaceutical for prostate cancer, [225Ac]Ac-Macropa-PEG4-YS5, in mice. 22Rv1 xenograft-bearing mice treated with 18.5 kBq of [225Ac]Ac-Macropa-PEG4-YS5 were sacrificed at 24 h and 168 h post-injection for quantitative α\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upalpha$$\\end{document}-particle digital autoradiography and hematoxylin and eosin staining. Gamma-ray spectroscopy of biodistribution data was used to determine temporal dynamics and 213\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{213}$$\\end{document}Bi redistribution. Tumor control probability and sub-kidney dosimetry were assessed. Heterogeneous 225\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{225}$$\\end{document}Ac spatial distribution was observed in both tumors and kidneys. Tumor control was maintained despite heterogeneity if cold spots coincided with necrotic regions. 225\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{225}$$\\end{document}Ac dose-rate was highest in the cortex and renal vasculature. Extrapolation of tumor control suggested that kidney absorbed dose could be reduced by 41% while maintaining 90% TCP. The 3D dosimetry methods described allow for whole tumor and organ dose measurements following 225\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{225}$$\\end{document}Ac radiopharmaceutical therapy, which correlate to tumor control and toxicity outcomes.

Characterizing the voxel-based approaches in radioembolization dosimetry with reDoseMC.

Yttrium-90 ( ) represents the primary radioisotope used in radioembolization procedures, while holmium-166 ( ) is hypothesized to serve as a viable substitute for due to its comparable therapeutic potential and improved quantitative imaging. Voxel-based dosimetry for these radioisotopes relies on activity images obtained through PET or SPECT and dosimetry methods, including the voxel S-value (VSV) and the local deposition method (LDM). However, the evaluation of the accuracy of absorbed dose calculations has been limited by the use of non-ideal reference standards and investigations restricted to the liver. The objective of this study was to expand upon these dosimetry characterizations by investigating the impact of image resolutions, voxel sizes, target volumes, and tissue materials on the accuracy of and dosimetry techniques. A specialized radiopharmaceutical dosimetry software called reDoseMC was developed using the Geant4 Monte Carlo toolkit and validated by benchmarking the generated kernels with published data. The decay spectra of both and were also compared. Multiple VSV kernels were generated for the liver, lungs, soft tissue, and bone for isotropic voxel sizes of 1 mm, 2 mm, and 4 mm. Three theoretical phantom setups were created with 20 or 40mm activity and mass density inserts for the same three voxel sizes. To replicate the limited spatial resolutions present in PET and SPECT images, image resolutions were modeled using a 3D Gaussian kernel with a Full Width at Half Maximum (FWHM) ranging from 0 to 16mm and with no added noise. The VSV and LDM dosimetry methods were evaluated by characterizing their respective kernels and analyzing their absorbed dose estimates calculated on theoretical phantoms. The ground truth for these estimations was calculated usingreDoseMC. The decay spectra obtained through reDoseMC showed less than a 1% difference when compared to previously published experimental data for energies below 1.9MeV in the case of and less than 1% for energies below 1.5MeV for . Additionally, the validation kernels for VSV exhibited results similar to those found in published Monte Carlo codes, with source dose depositions having less than a 3% error margin. Resolution thresholds ( ), defined as resolutions that resulted in similar dose estimates between the LDM and VSV methods, were observed for . They were 1.5mm for bone, 2.5 mm for soft tissue and liver, and 8.5 mm for lungs. For , the accuracy of absorbed dose deposition was found to be dependent on the contributions of absorbed dose from photons. Volume errors due to variations in voxel size impacted the final dose estimates. Larger target volumes yielded more accurate mean doses than smaller volumes. For both radioisotopes, the radial dose profiles for the VSV and LDM approximated but never matched the referencestandard. reDoseMC was developed and validated for radiopharmaceutical dosimetry. The accuracy of voxel-based dosimetry was found to vary widely with changes in image resolutions, voxel sizes, chosen target volumes, and tissue material; hence, the standardization of dosimetry protocols was found to be of great importance for comparable dosimetryanalysis.

Developments in 177Lu-based radiopharmaceutical therapy and dosimetry.

177Lu is a radioisotope that has become increasingly popular as a therapeutic agent for treating various conditions, including neuroendocrine tumors and metastatic prostate cancer. 177Lu-tagged radioligands are molecules precisely designed to target and bind to specific receptors or proteins characteristic of targeted cancer. This review paper will present an overview of the available 177Lu-labelled radioligands currently used to treat patients. Based on recurring, active, and completed clinical trials and other available literature, we evaluate current status, interests, and developments in assessing patient-specific dosimetry, which will define the future of this particular treatment modality. In addition, we will discuss the challenges and opportunities of the existing dosimetry standards to measure and calculate the radiation dose delivered to patients, which is essential for ensuring treatments' safety and efficacy. Finally, this article intends to provide an overview of the current state of 177Lu- tagged radioligand therapy and highlight the areas where further research can improve patient treatment outcomes.

Updating 90Y Voxel S-Values including internal Bremsstrahlung: Monte Carlo study and development of an analytical model

PurposeInternal Bremsstrahlung (IB) is a process accompanying β-decay but neglected in Voxel S-Values (VSVs) calculation. Aims of this work were to calculate, through Monte Carlo (MC) simulation, updated 90Y-VSVs including IB, and to develop an analytical model to evaluate 90Y-VSVs for any voxel size of practical interest. MethodsGATE (Geant4 Application for Tomographic Emission) was employed for simulating voxelized geometries of soft tissue, with voxels sides l ranging from 2 to 6 mm, in steps of 0.5 mm. The central voxel was set as a homogeneous source of 90Y when IB photons are not modelled. For each l, the VSVs were computed for 90Y decays alone and for 90Y + IB. The analytical model was then built through fitting procedures of the VSVs including IB contribution. ResultsComparing GATE-VSVs with and without IB, differences between + 25% and + 30% were found for distances from the central voxel larger than the maximum β-range. The analytical model showed an agreement with MC simulations within ± 5% in the central voxel and in the Bremsstrahlung tails, for any l value examined, and relative differences lower than ± 40%, for other distances from the source. ConclusionsThe presented 90Y-VSVs include for the first time the contribution due to IB, thus providing a more accurate set of dosimetric factors for three-dimensional internal dosimetry of 90Y-labelled radiopharmaceuticals and medical devices. Furthermore, the analytical model constitutes an easy and fast alternative approach for 90Y-VSVs estimation for non-standard voxel dimensions.

MIRD Pamphlet No. 28, Part 2: Comparative Evaluation of MIRDcalc Dosimetry Software Across a Compendium of Diagnostic Radiopharmaceuticals.

Radiopharmaceutical dosimetry is usually estimated via organ-level MIRD schema-style formalisms, which form the computational basis for commonly used clinical and research dosimetry software. Recently, MIRDcalc internal dosimetry software was developed to provide a freely available organ-level dosimetry solution that incorporates up-to-date models of human anatomy, addresses uncertainty in radiopharmaceutical biokinetics and patient organ masses, and offers a 1-screen user interface as well as quality assurance tools. The present work describes the validation of MIRDcalc and, secondarily, provides a compendium of radiopharmaceutical dose coefficients obtained with MIRDcalc. Biokinetic data for about 70 currently and historically used radiopharmaceuticals were obtained from the International Commission on Radiological Protection (ICRP) publication 128 radiopharmaceutical data compendium. Absorbed dose and effective dose coefficients were derived from the biokinetic datasets using MIRDcalc, IDAC-Dose, and OLINDA software. The dose coefficients obtained with MIRDcalc were systematically compared against the other software-derived dose coefficients and those originally presented in ICRP publication 128. Dose coefficients computed with MIRDcalc and IDAC-Dose showed excellent overall agreement. The dose coefficients derived from other software and the dose coefficients promulgated in ICRP publication 128 both were in reasonable agreement with the dose coefficients computed with MIRDcalc. Future work should expand the scope of the validation to include personalized dosimetry calculations.

MIRD Pamphlet No. 28, Part 1: MIRDcalc-A Software Tool for Medical Internal Radiation Dosimetry.

Medical internal radiation dosimetry constitutes a fundamental aspect of diagnosis, treatment, optimization, and safety in nuclear medicine. The MIRD committee of the Society of Nuclear Medicine and Medical Imaging developed a new computational tool to support organ-level and suborgan tissue dosimetry (MIRDcalc, version 1). Based on a standard Excel spreadsheet platform, MIRDcalc provides enhanced capabilities to facilitate radiopharmaceutical internal dosimetry. This new computational tool implements the well-established MIRD schema for internal dosimetry. The spreadsheet incorporates a significantly enhanced database comprising details for 333 radionuclides, 12 phantom reference models (International Commission on Radiological Protection), 81 source regions, and 48 target regions, along with the ability to interpolate between models for patient-specific dosimetry. The software also includes sphere models of various composition for tumor dosimetry. MIRDcalc offers several noteworthy features for organ-level dosimetry, including modeling of blood source regions and dynamic source regions defined by user input, integration of tumor tissues, error propagation, quality control checks, batch processing, and report-preparation capabilities. MIRDcalc implements an immediate, easy-to-use single-screen interface. The MIRDcalc software is available for free download (www.mirdsoft.org) and has been approved by the Society of Nuclear Medicine and Molecular Imaging.

Creation of waterproof, TLD probes for dose measurements to validate image-based radiopharmaceutical therapy dosimetry workflow

Voxel-level dosimetry based on nuclear medicine images offers patient-specific personalization of radiopharmaceutical therapy (RPT) treatments. Clinical evidence is emerging demonstrating improvements in treatment precision in patients when voxel-level dosimetry is used compared to MIRD. Voxel-level dosimetry requires absolute quantification of activity concentrations in the patient, but images from SPECT/CT scanners are not quantitative and require calibration using nuclear medicine phantoms. While phantom studies can validate a scanner’s ability to recover activity concentrations, these studies provide only a surrogate for the true metric of interest: absorbed doses. Measurements using thermoluminescent dosimeters (TLDs) are a versatile and accurate method of measuring absorbed dose. In this work, a TLD probe was manufactured that can fit into currently available nuclear medicine phantoms for the measurement of absorbed dose of RPT agents. Next, 748 MBq of I-131 was administered to a 16 ml hollow source sphere placed in a 6.4 L Jaszczak phantom in addition to six TLD probes, each holding 4 TLD-100 1 × 1 × 1 mm TLD-100 (LiF:Mg,Ti) microcubes. The phantom then underwent a SPECT/CT scan in accordance with a standard SPECT/CT imaging protocol for I-131. The SPECT/CT images were then input into a Monte Carlo based RPT dosimetry platform named RAPID and a three dimensional dose distribution in the phantom was estimated. Additionally, a GEANT4 benchmarking scenario (denoted ‘idealized’) was created using a stylized representation of the phantom. There was good agreement for all six probes, the differences between measurement and RAPID ranged between −5.5% and 0.9%. The difference between the measured and the idealized GEANT4 scenario was calculated and ranged from −4.3% and −20.5%. This work demonstrates good agreement between TLD measurements and RAPID. In addition, it introduces a novel TLD probe that can be easily introduced into clinical nuclear medicine workflows to provide QA of image-based dosimetry for RPT treatments.

Improved accuracy of S-value-based dosimetry: a guide to transition from Cristy–Eckerman to ICRP adult phantoms

BackgroundIn 2016, the International Commission on Radiological Protection (ICRP) published the results of Monte Carlo simulations performed using updated and anatomically realistic voxelized phantoms. The resulting specific absorbed fractions are based on more realistic human anatomy than those computed in the stylized, geometrical Cristy–Eckerman (CE) phantom. Despite this development, the ICRP-absorbed fractions have not been widely adopted for radiopharmaceutical dosimetry. To help make the transition, we have established a correspondence between source and target tissues defined in the CE phantom and those defined in the ICRP phantoms.ResultsThe ICRP phantom has 79 source regions and 43 target regions in comparison with the 23 source and 18 target tissue regions defined in the CE phantom. The ICRP phantom provides tissue regions with greater anatomical detail. Some of this additional detail is focused on radiation protection and dosimetry of inhaled/ingested radioactivity. Some, but not all, of this detail is useful and appropriate for radiopharmaceutical therapy. We have established the correspondence between CE and ICRP phantom source and target regions and attempted to highlight the ICRP source tissues relevant to radiopharmaceutical therapy (RPT). This paper provides tables and figures highlighting the correspondences established.ConclusionThe results provide assistance in transitioning from CE-stylized phantoms to the anatomically accurate voxelized ICRP phantoms. It provides specific guidance for porting the total absorbed activity for regions as defined in the CE phantom to regions within the ICRP phantoms.

Challenges and opportunities in developing Actinium-225 radiopharmaceuticals.

Actinium-225 (225Ac) has emerged as a promising therapeutic radioisotope for targeted alpha therapy. It emits net four alpha particles during its decay to stable daughter bismuth-209, rightly called an in-vivo nano-generator. Compared to the worldwide demand of 225Ac, the amount produced via depleted thorium-229 sources is minimal, making it an expensive radionuclide. However, many research groups are working on optimizing the parameters for the production of 225Ac via different routes, including cyclotrons, reactors and high-energy linear accelerators. The present review article focuses on the various aspects associated with the development of 225Ac radiopharmaceuticals. It includes the challenges and opportunities associated with the production methods, labeling chemistry, in-vivo kinetics and dosimetry of 225Ac radiopharmaceuticals. A brief description is also given about the 225Ac radiopharmaceuticals at preclinical stages, clinical trials and used routinely.

Theranostics: an integrated imaging and therapies for personalized nuclear medicine

Synopsis: Theranostics, a pairing of diagnostic biomarkers with therapeutic agents, was first introduced into nuclear medicine in 1940’s to identify the relevant molecular targets in cancer for the treatment and imaging on thyroid cancer patients with radioactive iodide-131 or RAI. Among several radionuclides used for theranostics, Lutetium-177 (177Lu), the beta-emitter, has been recognized as a radioisotope that widely used for therapeutic agent in targeted radionuclide therapy. This talk aims to review and explore the emerging radionuclides that widely used for theranostics in nuclear medicine. Radiopharmaceutical dosimetry and personalized treatment planning will also be provided in this presentation.

Abstract IACC0601: Radiopharmaceuticals and their future in cancer care

Abstract Radiopharmaceutical agents have been an appealing treatment approach since the use of 131I to treat thyroid malignancies. Advances in cancer radiobiology and radiochemistry have brought radiopharmaceuticals forward to the cutting edge of oncology clinical research. The National Cancer Institute (NCI) and its partnering academic and clinical research networks monitor radiopharmaceutical discoveries that might be incorporated into cancer treatment strategies for patients with unmet therapeutic needs. Such endeavors happen through leveraged partnerships between NCI's Cancer Therapy Evaluation Program (CTEP), its Radiation Research Program (RRP), and academic institutions in the Experimental Therapeutics Clinical Trials Network (ETCTN). If innovative discoveries are made, NCI supports clinician scientists to plan new and original radiopharmaceutical phase I and II monotherapy or combination trials. The clinical trial infrastructure needs, such as radiopharmaceutical dosimetry and treatment planning, are now available in government workflow and regulatory oversight. This presentation introduces a modern approach to the clinical development of radiopharmaceutical agents in an era of molecular targets and personalized cancer therapeutics. Citation Format: Charles A. Kunos. Radiopharmaceuticals and their future in cancer care [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr IACC0601.

Reimbursement Approaches for Radiopharmaceutical Dosimetry: Current Status and Future Opportunities.

Interest in performing dosimetry for clinical radiopharmaceutical therapy procedures has grown in recent years. Several approved therapies include dosimetry in the Food and Drug Administration-approved label instructions, and other therapies are best used under a patient-tailored paradigm. This paper, which is a product of the Society of Nuclear Medicine and Molecular Imaging Dosimetry Task Force, presents motivations and general workflows for radiopharmaceutical therapy dosimetry, as well as existing strategies for obtaining reimbursement for clinical activities related to dosimetry. Several specific patient examples are provided, including suggested codes for reimbursement. In addition to current reimbursement approaches, key dosimetry services that are not supported under the current coding structure are presented and suggested as areas of focus in the coming years.

Perspectives on Internal Dosimetry for Optimized Radionuclide Therapy.

Abstract A balanced approach to radiopharmaceutical dosimetry involves personalized dosimetry. Planar quantitative imaging can be practical, reliable, and relatively cost-effective. Therapy dose optimization can be achieved for the individual patient using a straightforward tracer study to determine patient-specific biokinetics at three or more imaging time points for organs that assimilate the radiopharmaceutical. Two-dimensional quantitative imaging may be supported and calibrated using a 3D SPECT/CT measurement for the dose-limiting organ at a single time point. Organ volumes are needed from CT images. Measurements require special attention for consistency in camera-to-patient distancing, region-of-interest delineation, and attenuation correction, and operators need training and experience well beyond the requirements for standard nuclear medicine scintigraphy. As with external beam therapy, reimbursement codes are needed to support treatment-planning costs. Postinfusion tumor dosimetry can be important in overall evaluation of radionuclide therapy effectiveness. Clinicians and pharmaceutical companies should recognize the value of a balanced approach to personalized internal dosimetry for maximizing therapy benefit while minimizing toxicity. Prospective clinical trials should employ quantitative dosimetry with standardized methodologies to deliver predictive paradigms and establish the efficacy of new radioimmunotherapy products.

RADAR Guide: Standard Methods for Calculating Radiation Doses for Radiopharmaceuticals, Part 1-Collection of Data for Radiopharmaceutical Dosimetry.

This paper presents standardized methods for collecting data to be used in performing dose calculations for radiopharmaceuticals. Various steps in the process are outlined, with some specific examples given. This document can be used as a template for designing and executing kinetic studies for calculating radiation dose estimates, from animal or human data.

Dosimetry of radiopharmaceuticals used in adult patients with suspected pulmonary embolism

The absorbed dose of radiopharmaceuticals is estimated in adults with suspected pulmonary embolism explored by ventilation/perfusion studies. For pulmonary ventilation studies 81mKr, 133Xe, 99mTc (Technegas)-aerosol and 99mTc (DTPA)-aerosol are used. For perfusion agents, 99mTc(MAA), 99mTc (MSA) (macroaggregates and albumin microspheres) are used. For the dose calculation, the MIRD methodology and the anthropomorphic representation of the biokinetic organs of Cristy-Eckerman are used. In ventilation/perfusion studies, the lowest dose absorbed by the lungs with suspected embolism is due to 81mKr/ 99mTc (MSA), and the highest dose is due to 99mTc (Technegas)/99mTc (MAA) calculated for activities of 150 MBq for perfusion agents and 40 MBq for ventilation agents.

Feasibility of Single-Time-Point Dosimetry for Radiopharmaceutical Therapies.

Because of challenges in performing routine personalized dosimetry in radiopharmaceutical therapies, interest in single-time-point (STP) dosimetry, particularly using only a single SPECT scan, is on the rise. Meanwhile, there are questions about the reliability of STP dosimetry, with limited independent validations. In the present work, we analyzed 2 STP dosimetry methods and evaluated dose errors for several radiopharmaceuticals based on effective half-life distributions. Methods: We first challenged the common assumption that radiopharmaceutical effective half-lives across the population are gaussian-distributed (i.e., follow a normal distribution). Then, dose accuracy was estimated using 2 STP dosimetry methods for a wide range of potential post injection (p.i.) scan time points for different radiopharmaceuticals applied to neuroendocrine tumors and prostate cancer. The accuracy and limitations of each of the STP methods were discussed. Results: A lognormal distribution was more appropriate for capturing effective half-life distributions. The STP framework was promising for dosimetry of 177Lu-DOTATATE and for kidney dosimetry of different radiopharmaceuticals (errors < 30%). Meanwhile, for some radiopharmaceuticals, STP accuracy was compromised (e.g., in bone marrow and tumors for 177-labeled prostate-specific membrane antigen [PSMA])). The optimal SPECT scanning time for 177Lu-DOTATATE was approximately 72 h p.i., whereas 48h p.i. was better for 177Lu-PSMA. Conclusion: Simplified STP dosimetry methods may compromise the accuracy of dose estimates, with some exceptions, such as for 177Lu-DOTATATE and for kidney dosimetry in different radiopharmaceuticals. Simplified personalized dosimetry in the clinic continues to be challenging. On the basis of our results, we make suggestions and recommendations for improved personalized dosimetry using simplified imaging schemes.

OpenDose: Open-Access Resource for Nuclear Medicine Dosimetry.

Radiopharmaceutical dosimetry depends on the localization in space and time of radioactive sources and requires the estimation of the amount of energy emitted by the sources deposited within targets. In particular, when computing resources are not accessible, this task can be performed using precomputed tables of specific absorbed fractions (SAFs) or S values based on dosimetric models. The aim of the OpenDose collaboration is to generate and make freely available a range of dosimetric data and tools. Methods: OpenDose brings together resources and expertise from 18 international teams to produce and compare traceable dosimetric data using 6 of the most popular Monte Carlo codes in radiation transport (EGSnrc/EGS++, FLUKA, GATE, Geant4, MCNP/MCNPX, and PENELOPE). SAFs are uploaded, together with their associated statistical uncertainties, in a relational database. S values are then calculated from monoenergetic SAFs on the basis of the radioisotope decay data presented in International Commission on Radiological Protection Publication 107. Results: The OpenDose collaboration produced SAFs for all source region and target combinations of the 2 International Commission on Radiological Protection Publication 110 adult reference models. SAFs computed from the different Monte Carlo codes were in good agreement at all energies, with SDs below individual statistical uncertainties. Calculated S values were in good agreement with OLINDA/EXM 2.0 (commercial) and IDAC-Dose 2.1 (free) software. A dedicated website (www.opendose.org) has been developed to provide easy and open access to all data. Conclusion: The OpenDose website allows the display and downloading of SAFs and the corresponding S values for 1,252 radionuclides. The OpenDose collaboration, open to new research teams, will extend data production to other dosimetric models and implement new free features, such as online dosimetric tools and patient-specific absorbed dose calculation software, together with educational resources.

Radiation Dose Does Matter: Mechanistic Insights into DNA Damage and Repair Support the Linear No-Threshold Model of Low-Dose Radiation Health Risks

1014 Objectives: Human internal dosimetry of new radiopharmaceuticals should have presumed by the animal data. Cu-64 labeled radiopharmaceuticals has possibly can use PET imaging and therapeutic effect assuming of convergence radiopharmaceutical. The aim of this study has evaluated the Cu-64 labeled radiopharmaceutical projected human internal dosimetry using small animal biodistribution and image data. Methods: Cu-64 labeled radiopharmaceutical PET image was acquired using small animal PET/CT system (Inveon, Siemens Healthcare.) in mouse (n = 3) at 1, 2, 6, 24, 48 and 72 hour after intravenous injection of Cu-64 labeled radiopharmaceutical. Each organ region was defined by contrast mouse CT image (Exitron nano 12000, Miltenyi Biotec). In this study, three internal dosimetry method which are animal derived, human extrapolated, and object specific dosimetry. Animal derived dosimetry method was estimated by estimated biodistribution in mouse and human S-value. Human extrapolate dosimetry method was calculated extrapolated human biodistribution and human S-value. Object specific dosimetry method was calculated using image based residence time and object specific S-value. Object specific S-value was calculated based on individual small animal CT image using Monte Carlo simulation. Results: Animal derived absorbed dose in heart, lung, liver, spleen were 0.048 ± 0.006, 0.028 ± 0.012, 0.079 ± 0.002, 0.047 ± 0.005 mGy/MBq, respectively. Human extrapolated absorbed dose were 0.054 ± 0.007 for heart, 0.102 ± 0.017 for lung, 0.118 ± 0.012 for liver, and 0.100 ± 0.013 mGy/MBq for spleen. Object specific absorbed dose were 0.053 ± 0.006 for heart, 0.027 ± 0.005 for lung, 0.035 ± 0.005 for liver, 0.025 ± 0.003 mGy/MBq for spleen. According to the absorbed dose, extrapolate dosimetry method has more higher estimated Cu-64 absorbed dose in lung, liver, spleen region than animal derived and object specific dosimetry Methods: Conclusion: We evaluated the human projected internal dosimetry using Cu-64 small animal data. Human extrapolated dose was overestimated in lung, liver, and spleen. Object specific dosimetry will be applied for diagnostic and therapeutic human dose calculation.

National Cancer Institute Programmatic Collaboration for Investigational Radiopharmaceuticals.

Radiopharmaceutical therapies have provided an attractive therapeutic approach since the introduction of 131I to treat thyroid cancer. New insights in cancer biology and radiochemistry have brought radiopharmaceuticals to the leading edge of oncology clinical research. National Cancer Institute (NCI) programs watch for new radiopharmaceutical breakthroughs that should be used to treat patients with unmet therapeutic needs. Such efforts occur through leveraged partnerships between NCI's Cancer Therapy Evaluation Program and its Radiation Research Program. If groundbreaking discoveries are made, NCI pulls together clinician scientists to design novel radiopharmaceutical phase I and II monotherapy or combination trials. The specific infrastructure needs, such as radiopharmaceutical dosimetry and treatment planning, demand new programmatic workflow and regulatory oversight. This article discusses a modern approach to the development of radiopharmaceutical therapies in the era of personalized medicine.

Abstract ID: 155 OpenDose: A collaborative effort to produce reference dosimetric data with Monte Carlo simulation software

Radiopharmaceutical dosimetry for diagnostic and therapy uses reference data describing energy deposition from a source to target tissues. Reference data are usually expressed as S-values, i.e. mean absorbed dose in a target from a source decay (Gy.Bq-1.s-1). The OpenDose project aims at providing an open database of robust reference S-values generated from different Monte Carlo (MC) software, through an international collaboration. The ICRP 110 reference adult female [1] was chosen as the first model, with 140 segmented tissues-organs and a voxel size of 1.775 × 1.775 × 4.84 mm3. Specific Absorbed Fractions (SAFs) are being computed for different sources, with mono-energetic photons and electrons. S-values will be generated by interpolating these mono-energetic SAFs for isotope decay schemes [2] . Producing data with different software using various physics lists will allow a cross-verification of the results and their associated uncertainties. The OpenDose project already includes 12 research teams and 5 of the most popular MC software used in radiopharmaceutical dosimetry: Geant4/GATE, Fluka, EGSnrc/EGS++, MCNP/MCNPX and Penelope. A total of 46 source tissues-organs have so far been simulated with GATE for mono-energetic particles (photons + electrons) from 5 keV to 10 MeV. Each simulation requires ∼ 1 day of computation on a single CPU for 108 primary particles and produces a 3D map (voxel-based) of absorbed doses and uncertainties. When available, the data from the other software will be analysed and compared in terms of SAFs for different targets and energies. Next steps include the integration of SAFs to provide S-values and build the database to allow Nuclear Medicine centres to easily access and use the data. Through a collaboration of research teams using different MC techniques, we are developing a freely accessible database of reference dosimetric data. A preliminary study using the ICRP adult female model is ongoing. The project is open to new research teams to increase the variety of software and will expand to more computational models and studies.