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Title: SU-C-204-03: DFT Calculations of the Stability of DOTA-Based-Radiopharmaceuticals

Abstract

Purpose: Application of the density function theory (DFT) to investigate the structural stability of complexes applied in cancer therapy consisting of the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated to Ac225, Fr221, At217, Bi213, and Gd68 radio-nuclei. Methods: The possibility to deliver a toxic payload directly to tumor cells is a highly desirable aim in targeted alpha particle therapy. The estimation of bond stability between radioactive atoms and the DOTA chelating agent is the key element in understanding the foundations of this delivery process. Thus, we adapted the Vienna Ab-initio Simulation Package (VASP) with the projector-augmented wave method and a plane-wave basis set in order to study the stability and electronic properties of DOTA ligand chelated to radioactive isotopes. In order to count for the relativistic effect of radioactive isotopes we included Spin-Orbit Coupling (SOC) in the DFT calculations. Five DOTA complex structures were represented as unit cells, each containing 58 atoms. The energy optimization was performed for all structures prior to calculations of electronic properties. Binding energies, electron localization functions as well as bond lengths between atoms were estimated. Results: Calculated binding energies for DOTA-radioactive atom systems were −17.792, −5.784, −8.872, −13.305, −18.467 eV for Ac, Fr, At, Bi and Gd complexesmore » respectively. The displacements of isotopes in DOTA cages were estimated from the variations in bond lengths, which were within 2.32–3.75 angstroms. The detailed representation of chemical bonding in all complexes was obtained with the Electron Localization Function (ELF). Conclusion: DOTA-Gd, DOTA-Ac and DOTA-Bi were the most stable structures in the group. Inclusion of SOC had a significant role in the improvement of DFT calculation accuracy for heavy radioactive atoms. Our approach is found to be proper for the investigation of structures with DOTA-based-radiopharmaceuticals and will enhance our understanding of processes occurring at subatomic levels.« less

Authors:
;  [1]; ; ;  [2]; ;  [1];  [3]
  1. University of South Florida, Tampa, Florida (United States)
  2. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States)
  3. (United States)
Publication Date:
OSTI Identifier:
22624301
Resource Type:
Journal Article
Resource Relation:
Journal Name: Medical Physics; Journal Volume: 43; Journal Issue: 6; Other Information: (c) 2016 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 60 APPLIED LIFE SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; ACTINIUM 225; ASTATINE 217; BINDING ENERGY; BISMUTH 213; BOND LENGTHS; CHELATES; CHELATING AGENTS; CHEMICAL BONDS; FRANCIUM 221; GADOLINIUM COMPLEXES; NEOPLASMS; PARTICLE BEAMS; RADIOPHARMACEUTICALS; RADIOTHERAPY; RELATIVISTIC RANGE; TUMOR CELLS

Citation Formats

Khabibullin, A.R., Woods, L.M., Karolak, A., Budzevich, M.M., Martinez, M.V., McLaughlin, M.L., Morse, D.L., and H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. SU-C-204-03: DFT Calculations of the Stability of DOTA-Based-Radiopharmaceuticals. United States: N. p., 2016. Web. doi:10.1118/1.4955536.
Khabibullin, A.R., Woods, L.M., Karolak, A., Budzevich, M.M., Martinez, M.V., McLaughlin, M.L., Morse, D.L., & H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. SU-C-204-03: DFT Calculations of the Stability of DOTA-Based-Radiopharmaceuticals. United States. doi:10.1118/1.4955536.
Khabibullin, A.R., Woods, L.M., Karolak, A., Budzevich, M.M., Martinez, M.V., McLaughlin, M.L., Morse, D.L., and H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. Wed . "SU-C-204-03: DFT Calculations of the Stability of DOTA-Based-Radiopharmaceuticals". United States. doi:10.1118/1.4955536.
@article{osti_22624301,
title = {SU-C-204-03: DFT Calculations of the Stability of DOTA-Based-Radiopharmaceuticals},
author = {Khabibullin, A.R. and Woods, L.M. and Karolak, A. and Budzevich, M.M. and Martinez, M.V. and McLaughlin, M.L. and Morse, D.L. and H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida},
abstractNote = {Purpose: Application of the density function theory (DFT) to investigate the structural stability of complexes applied in cancer therapy consisting of the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated to Ac225, Fr221, At217, Bi213, and Gd68 radio-nuclei. Methods: The possibility to deliver a toxic payload directly to tumor cells is a highly desirable aim in targeted alpha particle therapy. The estimation of bond stability between radioactive atoms and the DOTA chelating agent is the key element in understanding the foundations of this delivery process. Thus, we adapted the Vienna Ab-initio Simulation Package (VASP) with the projector-augmented wave method and a plane-wave basis set in order to study the stability and electronic properties of DOTA ligand chelated to radioactive isotopes. In order to count for the relativistic effect of radioactive isotopes we included Spin-Orbit Coupling (SOC) in the DFT calculations. Five DOTA complex structures were represented as unit cells, each containing 58 atoms. The energy optimization was performed for all structures prior to calculations of electronic properties. Binding energies, electron localization functions as well as bond lengths between atoms were estimated. Results: Calculated binding energies for DOTA-radioactive atom systems were −17.792, −5.784, −8.872, −13.305, −18.467 eV for Ac, Fr, At, Bi and Gd complexes respectively. The displacements of isotopes in DOTA cages were estimated from the variations in bond lengths, which were within 2.32–3.75 angstroms. The detailed representation of chemical bonding in all complexes was obtained with the Electron Localization Function (ELF). Conclusion: DOTA-Gd, DOTA-Ac and DOTA-Bi were the most stable structures in the group. Inclusion of SOC had a significant role in the improvement of DFT calculation accuracy for heavy radioactive atoms. Our approach is found to be proper for the investigation of structures with DOTA-based-radiopharmaceuticals and will enhance our understanding of processes occurring at subatomic levels.},
doi = {10.1118/1.4955536},
journal = {Medical Physics},
number = 6,
volume = 43,
place = {United States},
year = {Wed Jun 15 00:00:00 EDT 2016},
month = {Wed Jun 15 00:00:00 EDT 2016}
}
  • Purpose: Large animal models, most popularly beagles, have been crucial surrogates to humans in determining radiation safety levels of radiopharmaceuticals. This study aims to develop a detailed beagle phantom to accurately approximate organ absorbed doses for therapy nuclear medicine preclinical studies. Methods: A 3D NURBS model was created subordinate to a whole body CT of an adult beagle. Bones were harvested and CT imaged to offer macroscopic skeletal detail. Samples of trabecular spongiosa were cored and imaged to offer microscopic skeletal detail for bone trabeculae and marrow volume fractions. Results: Organ masses in the model are typical of an adultmore » beagle. Trends in volume fractions for skeletal dosimetry are fundamentally similar to those found in existing models of other canine species. Conclusion: This work warrants its use in further investigations of radiation transport calculation for electron and photon dosimetry. This model accurately represents the anatomy of a beagle, and can be directly translated into a useable geometry for a voxel-based Monte Carlo radiation transport program such as MCNP6. Work supported by a grant from the Hyundai Hope on Wheels Foundation for Pediatric Cancer Research.« less
  • Purpose: To study if prompt gamma (PG) volume histograms created from PG images acquired during treatment delivery can be used to identify changes to beam range and tissue composition in response to proton radiotherapy. Methods: Monte Carlo simulations of a single field from a single treatment fraction (100 cGy) for prostate cancer were performed for the cases of: 1) an ideal patient setup, 1) a setup shift in the superior direction and 2) a reduction in oxygen concentration in the tumor. For each case, the 3 -Dimsional dose delivery and elemental PG emission in the patient for the treatment fractionmore » were recorded and imported into a commercial treatment planning system. Changes in the dose volume histograms (DVH), as well as the PG volume histograms (PG-VH) for the PG emission from oxygen and for the total PG emission (from all elements) were analyzed. Results: For the 1 cm superior shift, the prostate DVH and total PG-VH both shifted toward lower doses with the shape of the curves remaining nearly unchanged, resulting in the DVH V95 dropping from 100 cGy to 90 cGy. For the total PG-VH, the V95 fell from 50 to 38. For the reduced oxygen case, both the DVH and PG-VH had a much different shape than for the ideal case, with a significant downward slope in the curves as a function of dose. Conclusions: The shift in the prostate PG-VH for a superior shift in the patient setup correlated well with the DVH indicating it is possible to detect setup errors by analyzing the PG-VH from prompt gamma images obtained during daily proton treatment delivery. Additionally, it may be possible to detect changes in the elemental concentrations of irradiated tissues by analyzing the shape of the PG-VH.« less
  • Purpose: Commonly used radiopharmaceuticals were tested to define the most important dosimetric factors in preclinical studies. Dosimetric calculations were applied in two different whole-body mouse models, with varying organ size, so as to determine their impact on absorbed doses and S-values. Organ mass influence was evaluated with computational models and Monte Carlo(MC) simulations. Methods: MC simulations were executed on GATE to determine dose distribution in the 4D digital MOBY mouse phantom. Two mouse models, 28 and 34 g respectively, were constructed based on realistic preclinical exams to calculate the absorbed doses and S-values of five commonly used radionuclides in SPECT/PETmore » studies (18F, 68Ga, 177Lu, 111In and 99mTc).Radionuclide biodistributions were obtained from literature. Realistic statistics (uncertainty lower than 4.5%) were acquired using the standard physical model in Geant4. Comparisons of the dosimetric calculations on the two different phantoms for each radiopharmaceutical are presented. Results: Dose per organ in mGy was calculated for all radiopharmaceuticals. The two models introduced a difference of 0.69% in their brain masses, while the largest differences were observed in the marrow 18.98% and in the thyroid 18.65% masses.Furthermore, S-values of the most important target-organs were calculated for each isotope. Source-organ was selected to be the whole mouse body.Differences on the S-factors were observed in the 6.0–30.0% range. Tables with all the calculations as reference dosimetric data were developed. Conclusion: Accurate dose per organ and the most appropriate S-values are derived for specific preclinical studies. The impact of the mouse model size is rather high (up to 30% for a 17.65% difference in the total mass), and thus accurate definition of the organ mass is a crucial parameter for self-absorbed S values calculation.Our goal is to extent the study for accurate estimations in small animal imaging, whereas it is known that there is a large variety in the anatomy of the organs.« less
  • Purpose: In computed tomography (CT) imaging, radiation dose delivered to the patient is one of the major concerns. Sparse-view CT takes projections at sparser view angles and provides a viable option to reducing dose. However, a fast power switching of an X-ray tube, which is needed for the sparse-view sampling, can be challenging in many CT systems. We have earlier proposed a many-view under-sampling (MVUS) technique as an alternative to sparse-view CT. In this study, we investigated the effects of collimator parameters on the image quality and aimed to optimize the collimator design. Methods: We used a bench-top circular cone-beammore » CT system together with a CatPhan600 phantom, and took 1440 projections from a single rotation. The multi-slit collimator made of tungsten was mounted on the X-ray source for beam blocking. For image reconstruction, we used a total-variation minimization (TV) algorithm and modified the backprojection step so that only the measured data through the collimator slits are to be used in the computation. The number of slits and the reciprocation frequency have been varied and the effects of them on the image quality were investigated. We also analyzed the sampling efficiency: the sampling density and data incoherence in each case. We tested three sets of slits with their number of 6, 12 and 18, each at reciprocation frequencies of 10, 30, 50 and 70 Hz/ro. Results: Consistent results in the image quality have been produced with the sampling efficiency, and the optimum condition was found to be using 12 slits at 30 Hz/ro. As image quality indices, we used the CNR and the detectability. Conclusion: We conducted an experiment with a moving multi-slit collimator to realize a sparse-sampled cone-beam CT. Effects of collimator parameters on the image quality have been systematically investigated, and the optimum condition has been reached.« less
  • Purpose: Metal implants such as orthopedic hardware and dental fillings cause severe bright and dark streaking in reconstructed CT images. These artifacts decrease image contrast and degrade HU accuracy, leading to inaccuracies in target delineation and dose calculation. Additionally, such artifacts negatively impact patient set-up in image guided radiation therapy (IGRT). In this work, we propose a novel method for metal artifact reduction which utilizes the anatomical similarity between neighboring CT slices. Methods: Neighboring CT slices show similar anatomy. Based on this anatomical similarity, the proposed method replaces corrupted CT pixels with pixels from adjacent, artifact-free slices. A gamma map,more » which is the weighted summation of relative HU error and distance error, is calculated for each pixel in the artifact-corrupted CT image. The minimum value in each pixel’s gamma map is used to identify a pixel from the adjacent CT slice to replace the corresponding artifact-corrupted pixel. This replacement only occurs if the minimum value in a particular pixel’s gamma map is larger than a threshold. The proposed method was evaluated with clinical images. Results: Highly attenuating dental fillings and hip implants cause severe streaking artifacts on CT images. The proposed method eliminates the dark and bright streaking and improves the implant delineation and visibility. In particular, the image non-uniformity in the central region of interest was reduced from 1.88 and 1.01 to 0.28 and 0.35, respectively. Further, the mean CT HU error was reduced from 328 HU and 460 HU to 60 HU and 36 HU, respectively. Conclusions: The proposed metal artifact reduction method replaces corrupted image pixels with pixels from neighboring slices that are free of metal artifacts. This method proved capable of suppressing streaking artifacts, improving HU accuracy and image detectability.« less