MIRD Committee Research Articles

Effect of Patient Morphology on Dosimetric Calculations for Internal Irradiation as Assessed by Comparisons of Monte Carlo Versus Conventional Methodologies

Dosimetric calculations are performed with an increasing frequency before or after treatment in targeted radionuclide therapy, as well as for radiation protection purposes in diagnostic nuclear medicine. According to the MIRD committee formalism, the mean absorbed dose to a target is given by the product of the cumulated activity and a dose-conversion factor, known as the S factor. Standard S factors have been published for mathematic phantoms and for unit-density spheres. The accuracy of the results from the use of these S factors is questionable, because patient morphology can vary significantly. The aim of this work was to investigate differences between patient-specific dosimetric results obtained using Monte Carlo methodology and results obtained using S factors calculated on standard models. The CT images of 9 patients, who ranged in size, were used. Patient-specific S factors for 131I were calculated with the MCNPX2.5.0 Monte Carlo code using a tool for personalized internal dose assessment, OEDIPE; standard S factors from OLINDA/EXM were compared against the patient-specific S factors. Furthermore, realistic biodistributions and cumulated activities for normal organs and tumors were used, and mean organ- and tumor-absorbed doses calculated with OEDIPE and OLINDA/EXM were compared. The ratio of the standard and the patient-specific S factors were between 0.49 and 1.84 for a target distant from the source for 4 organs and 2 tumors studied as source and targets. For the case of self-irradiation, the equivalent ratio ranged between 0.45 and 2.47 and between 1.00 and 1.06 when mass correction was applied. Differences in mean absorbed doses were as high as 140% when realistic cumulated activity values were used. These values decreased to less than 26% in all cases studied when mass correction was applied to the self-irradiation given by OLINDA/EXM. Standard S factors can yield mean absorbed doses for normal organs or tumors with a reasonable accuracy (26% for the cases studied) as compared with absorbed doses calculated with Monte Carlo, provided that they have been corrected for mass.

Biodistribution and Radiation Dosimetry of the Synthetic Nonmetabolized Amino Acid Analogue Anti-18F-FACBC in Humans

The synthetic leucine amino acid analog anti-1-amino-3-(18)F-fluorocyclobutane-1-carboxylic acid (anti-(18)F-FACBC) is a recently developed ligand that permits the evaluation of the L-amino acid transport system. This study evaluated the whole-body radiation burden of anti-(18)F-FACBC in humans. Serial whole-body PET/CT scans of 6 healthy volunteers (3 male and 3 female) were acquired for 2 h after a bolus injection of anti-(18)F-FACBC (366 +/- 51 MBq). Organ-specific time-activity curves were extracted from the reconstructed data and integrated to evaluate the individual organ residence times. A uniform activity distribution was assumed in the body organs with urine collection after the study. Estimates of radiation burden to the human body were calculated on the basis of the recommendations of the MIRD committee. The updated dynamic bladder model was used to calculate dose to the bladder wall. All volunteers showed initially high uptake in the pancreas and liver, followed by rapid clearance. Skeletal muscle and bone marrow showed lower and prolonged uptake, with clearance dominated by the tracer half-life. The liver was the critical organ, with a mean absorbed dose of 52.2 microGy/MBq. The estimated effective dose was 14.1 microSv/MBq, representing less than 20% of the dose limit recommended by the Radioactive Drug Research Committee for a 370-MBq injection. Bladder excretion was low and initially observed 6 min after injection, well after peak tracer uptake in the body organs. The PET whole-body dosimetry estimates indicate that an approximately 370-MBq injection of anti-(18)F-FACBC yields good imaging and acceptable dosimetry. The nonmetabolized nature of this tracer is favorable for extraction of relevant physiologic parameters from kinetic models.

Toward Patient-Friendly Cell-Level Dosimetry

Dosimetry for targeted radionuclide therapy is a relatively young field. Although initial work can be traced back to the late 1940s ( [1][1] ), the MIRD Committee formalism that forms the foundation for most current approaches was published in the mid 1970s ( [2][2] ), and the drive for improved

A Monte Carlo study of energy deposition at the sub-cellular level for application to targeted radionuclide therapy with low-energy electron emitters

Optimizing targeted radionuclide therapy for patients with circulating malignant cells (e.g. blood-related cancers) or a micrometastatic spread requires quantification of various dosimetric parameters at the single-cell level. We present results on the energy deposition of monoenergetic electrons of initial energy from 100eV to 20keV – relevant to Auger emitting radionuclides – distributed either uniformly or at the surface of spherical volumes of radii from 10nm to 1μm which correspond to critical sub-cellular targets. Calculations have been carried out by our detailed-history Monte Carlo (MC) code which simulates event-by-event the complete slowing down (to 1Ry) of both the primary and all subsequent generations of electrons, as well as, by the continuous-slowing-down-approximation (CSDA) using analytic range-energy relationships. The latter method has been adopted by the MIRD committee of the Society of Nuclear Medicine for dosimetry at the cellular level (>1μm). Differences between the MC and CSDA results are up to ∼50% and are expected to be even larger at higher energies and/or smaller volumes. They are attributed to the deficiencies of the CSDA method associated with the neglect of straggling and δ-ray transport. The results are particularly relevant to targeted radiotherapy at the genome level by Auger emitters.

Calculations of cellular microdosimetry parameters for alpha particles and electrons

The cellular microdosimetry parameters including the cellular S-value and the single-event specific energy distribution for alpha particles and electrons are important in radiation dosimetry and biology. These parameters may be used to determine the relative biological effectiveness of radiations in the boron neutron capture therapy. In the present work, such parameters were calculated for different source to target region combinations, i.e. cell surface, cytoplasm, nucleus and cell. Calculations were made using a semi-analytical model that simulated the emission of alpha particles or electrons by the Monte Carlo method and calculated the energy imparted to the target volume by the analytical method. Delta particle equilibrium and partial delta particle equilibrium were applied to alpha particles and electrons, respectively. Range–energy relations were employed to determine the incident and emerging energies of the primary particles. For electrons, the fraction in the energy loss resulting from the generation of bremsstrahlung and high-energy secondary electrons was estimated. The energy loss straggling of electrons entering and leaving a target volume was also estimated. Calculated cellular S-values were compared to corresponding data of the MIRD Committee. Calculated single-event specific energy distributions were also compared to results calculated using the Penelope code.

Dosimetry related to SPECT and PET applications

Nuclear medicine methods permit the in vivo measurement of physiological and metabolic functions. For this purpose metabolically active molecules are labelled with radionuclides. After the injection, these radiopharmaceuticals can be detected from outside the body with appropriate detectors such as conventional gamma cameras, single photon emission computerized tomographs (SPECT), or positron emission tomographs (PET). As with any application of ionizing radiation the benefits of nuclear medicine (the diagnosis and treatment of disease) must be balanced against the risks of the procedures. Risks in nuclear medicine are evaluated through dosimetry, the calculation of the radiation dose estimates, in which the energy deposited by the radiation in human tissues is quantitated. The first step of dosimetry is the determination of the biodistribution, i.e. the spatial and temporal distribution of the radiopharmaceutical within the body. When a new radiopharmaceutical is introduced such data are first derived from ex vivo experiments in animals. Further evaluations of the biokinetics and dosimetry are carried out via quantitative measurements in humans using the nuclear medicine imaging equipment, applying whole-body planar and tomographic methods. Based on the knowledge of the biodistribution and using the framework introduced by the MIRD committee as well as by the ICRP, the radiation dose to single organs and to the total body can be calculated. The purpose of this paper is to review methods for measuring radiopharmaceutical biodistributions in humans and for calculating the appropriate radiation dose quantities.

Dosimetry and microdosimetry of targeted radiotherapy.

Dosimetry in targeted radiotherapy (TR) uses different calculation methods, whose degree of refinement is closely conditioned by the particular objective sought. It is more generally performed to establish a correlation between the quantity of radiation delivered to a target and the biological damage observed or that can be reliably predicted. It can thus be used to optimise treatments and allow comparison of different therapeutic approaches, as well as to study the basic methods of irradiation of biological matter. Two broad types of investigations can be found in the literature: microdosimetric ones (stochastic approaches used to study energy deposits) and macrodosimetric ones (non-stochastic or deterministic approaches). The mathematical formalism is consistent between these two types, and the calculation methods currently used are often similar. This review presents different approaches to the dosimetry of radionuclides used in TR. The introduction defines the general problem, the role of dosimetry in TR and the specific problems raised by targeting (non-uniformity of source distributions). The first part considers the types of calculation methods found in TR in relation to the basic quantities used to represent stochastic energy deposit on a cellular scale. In particular, it compares the formalism and the methods used in microdosimetric or conventional macrodosimetric approches. Although microdosimetry, or even track structure calculations, can provide the basic elements for modelling the absorbed dose process, a simplified dosimetric approach may be adequate to describe the phenomena observed. The scheme proposed by the MIRD committee relates to such an approach and is presented together with other methods allowing the calculation of the mean dose delivered (analytic methods, dose point kernels, Monte-Carlo, etc.). The second part shows the application range for the various methods, providing selected examples of dosimetric approaches in TR on different scales, from the organ (or tissues) to the cell or even DNA, and a brief presentation of bone marrow dosimetry.

MABDOSE. I: Characterization of a general purpose dose estimation code.

The MABDOSE software represents a general tool to perform internal radiation dosimetry. It uses a three-dimensional lattice in which to conduct radiation transport, scoring energy deposition in discrete voxels. The dosimetry system currently relies on the same algorithm used by the MIRD committee for photon transport, and assumes local deposition of particulate energy. A mathematical description of the dosimetry system's implementation is given. Additionally, a characterization of the system with respect to memory requirements, data libraries used, and simulation timing benchmarks, is presented. Validation of the software is presented in a companion manuscript.

Computational methods in radionuclide dosimetry

The various approaches in radionuclide dosimetry depend on the size and spatial relation of the sources and targets considered in conjunction with the emission range of the radionuclide used. We present some of the frequently reported computational techniques on the basis of the source/target size. For whole organs, or for sources or targets bigger than some centimetres, the acknowledged standard was introduced 30 years ago by the MIRD committee and is still being updated. That approach, based on the absorbed fraction concept, is mainly used for radioprotection purposes but has been updated to take into account the dosimetric challenge raised by therapeutic use of vectored radiopharmaceuticals. At this level, the most important computational effort is in the field of photon dosimetry. On the millimetre scale, photons can often be disregarded, and or electron dosimetry is generally reported. Heterogeneities at this level are mainly above the cell level, involving groups of cell or a part of an organ. The dose distribution pattern is often calculated by generalizing a point source dose distribution, but direct calculation by Monte Carlo techniques is also frequently reported because it allows media of inhomogeneous density to be considered. At the cell level, and electron (low-range or Auger) are the predominant emissions examined. Heterogeneities in the dose distribution are taken into account, mainly to determine the mean dose at the nucleus. At the DNA level, Auger electrons or -particles are considered from a microdosimetric point of view. These studies are often connected with radiobiological experiments on radionuclide toxicity.

Radiation spectra for Auger-electron emitting radionuclides: report No. 2 of AAPM Nuclear Medicine Task Group No. 6.

Radiation spectra for radionuclides currently provided by the MIRD Committee and ICRP do not include the very low-energy N- and O-shell Auger electrons. These electrons, emitted in large numbers by radionuclides decaying by electron capture and/or internal conversion, are important for determining the absorbed dose in microscopic volumes. Accordingly, the present AAPM Report employs Monte Carlo computational methods to obtain a self-consistent set of complete radiation spectra for a variety of radionuclides including 55Fe, 67Ga, 99mTc, 111In, 113mIn, 115mIn, 123I, 125I, 193mPt, 195mPt, 201Tl, and 203Pb. Although the conventional spectra provided by MIRD and ICRP are adequate for most dosimetry calculations, the Auger electron spectra provided in this report are recommended for calculating the dose to target volumes < 1 microns in diameter.

Estimation of dose to the urinary bladder and to the gonads

The cellular microdosimetry parameters including the cellular S-value and the single-event specific energy distribution for alpha particles and electrons are important in radiation dosimetry and biology. These parameters may be used to determine the relative biological effectiveness of radiations in the boron neutron capture therapy. In the present work, such parameters were calculated for different source to target region combinations, i.e. cell surface, cytoplasm, nucleus and cell. Calculations were made using a semi-analytical model that simulated the emission of alpha particles or electrons by the Monte Carlo method and calculated the energy imparted to the target volume by the analytical method. Delta particle equilibrium and partial delta particle equilibrium were applied to alpha particles and electrons, respectively. Range–energy relations were employed to determine the incident and emerging energies of the primary particles. For electrons, the fraction in the energy loss resulting from the generation of bremsstrahlung and high-energy secondary electrons was estimated. The energy loss straggling of electrons entering and leaving a target volume was also estimated. Calculated cellular S-values were compared to corresponding data of the MIRD Committee. Calculated single-event specific energy distributions were also compared to results calculated using the Penelope code.

Estimation of whole body absorbed dose of the patient administered 57Co-bleomycin for tumor diagnosis.

The whole body absorbed dose of the patient administered 57Co-Bleomycin for tumor diagnosis was estimated in accordance with the MIRD Committee method. The whole body retention function was well described by the two component exponential model. The effective half-lives were several hours in the initial rapidly decreasing phase and 2-3 months in the successive slow phase. The accumulated whole body absorbed dose following intravenous administration of 1mCi of 57Co-Bleomycin was calculated to be approximately 3 rads, more than 90% of which was delivered in the first one year following injection. It was also revealed that no less than 99% of the dose was brought by the slow phase component, which indicated the importance of obtaining slow phase excretion date for dose estimation concerning the newly applied radiosubstances, irrespective of necessity or unneeessity for the diagnosis itself. Relatively high level of deposition was observed in the liver of a male patient of 82 years old who died of lung cancer 15 days after intravenous injection of 57Co-Bleomycin.