Unit Cumulated Activity Research Articles

Dosimetry assessment of theranostic Auger-emitting radionuclides in a micron-sized multicellular cluster model: A Monte Carlo study using Geant4-DNA simulations

The present work is aimed at improving the multicellular dosimetry of several Auger radionuclides of interest for targeted cancer therapy, including 99mTc, 111In, 123I, 125I, and 201Tl. For this purpose, using the Geant4-DNA Monte Carlo code, a cluster of 13 similar spherical cells with a hexagonal packed arrangement was modeled, and the mean absorbed doses per unit cumulated activity (S-values) were calculated by considering two target←source configurations, cell←cell and nucleus←nucleus. The obtained ratios of cross-dose to self-dose S-value in terms of the distance between the source and target regions were evaluated and also compared to those estimated by the Medical Internal Radiation Dose (MIRD) method. Besides, the contribution of the Coster-Kronig, Auger and internal conversion electrons to the S-values was provided for each radionuclide. According to the results, it can be concluded that in contrast to self-absorption, the cross-absorption due to the Auger-emitters has not a significant role in the total energy deposition within a cell in the cluster.

A Monte Carlo study on the effects of a static uniform magnetic field on micro-scale dosimetry of Auger-emitters using Geant4-DNA

In this work, an effort has been made to improve cellular dosimetry of Auger radionuclides through investigating any possible effect of an applied static uniform magnetic field (up to 10 T) on the absorbed doses of ionizing radiation in the micron-sized spherical volumes of liquid water per unit cumulated activity (S-values). The Geant4-DNA extension of the Geant4 Monte Carlo toolkit was employed to simulate the radioactive decay of several theranostic Auger-emitters, including 99mTc, 111In, 123I, 125I, and 201Tl which, distributed within various compartments of a typical spherical cell model. The S-values were calculated in the target regions belonging to both the cell containing the electron source (self-dose) and the second similar cell adjacent to it (cross-dose), with and without the presence of the magnetic field. The results related to the self- and cross-dose cases in the zero magnetic fields were compared to the corresponding MIRD ones. Based on the obtained results for the examined radionuclides and cell dimensions, it can be concluded that the self-dose values are not affected by a static uniform magnetic field, but the cross-dose ones increase slightly (up to 19%) depending on the orientation and strength of the magnetic field.

Cellular S values in spindle-shaped cells: a dosimetry study on more realistic cell geometries using Geant4-DNA Monte Carlo simulation toolkit

Cellular dosimetry plays a crucial role in radiobiology and evaluation of the relative merits of radiopharmaceuticals used for targeted radionuclide therapy. The present study aims to investigate the effects of various cell geometries on dosimetric characteristics of several Auger emitters distributed in different subcellular compartments using Monte Carlo simulation. The Geant4-DNA extension of the Geant4 Monte Carlo simulation toolkit was employed to calculate the mean absorbed dose per unit cumulated activity (S value) for different subcellular distributions of several Auger electron-emitting theranostic radionuclides including 99mTc, 111In, 123I, 125I, and 201Tl. The simulations were carried out in various single-cell models of liquid water including spherical, ellipsoidal, spherical spindle, and ellipsoidal spindle cell models. The latter two models which are generalized from the first two models were inspired by the morphologies of spindle-shaped (fusiform) cells, and were developed to provide more realistic modeling of this common geometry observed in many healthy and cancerous cells. Evaluation of the S values calculated for the examined cell models reveals that the differences are small (less than 9%) for the cell ← cell, cell ← cell surface, and nucleus ← nucleus source-target combinations. However, moderate discrepancies are seen (up to 28%) when the nucleus is considered as the target, as well as the radioactivity is either internalized into the cytoplasm or bound to the cell membrane. The findings of the present work suggest that the assumption of spherical cell geometry may provide reasonably accurate estimates of the cellular/nuclear dose for the considered Auger emitters, even for spindle-shaped cells. Of course, this approximation should be used with caution for the nucleus ← cytoplasm and nucleus ← cell surface configurations, since the S-value sensitivity to the cell geometry is somewhat significant in these cases.

Microdosimetry study of a multicellular model with mono-energetic electrons using Geant4-DNA simulation toolkit

Introduction: The goal of any type of radiation therapy in the treatment of tumors, in addition to destroying cancer cells, is to minimizing radiation to nearby healthy cells and thus reducing side damages. For this purpose, targeted radiation therapy (TRT) is more effective in treating of single cells or small cluster of cells. The main factor in the success of this method is that the range of charged particles used in treatment does not exceed the cellular dimensions; this justifies the use of electron emitters with the energy as low as possible (especially Auger electrons). Materials and Methods: In this study, the Monte Carlo simulation toolkit, Geant4-DNA, has been used due to the accurate computational models used to simulate the transport of charged particle at the cellular scale (micrometer and lower). So, with the help of this code, a multicellular model (cell cluster) consisting of five spherical cells (containing the nucleus) of liquid water, has been simulated in the medium of tissue material. One of the cells is considered as the source, and with the uniform random sampling of 100,000 mono-energetic electrons with an initial energy of 1-20 keV within this cell, energy deposition and the S-value (mean absorbed dose in the target per unit cumulated activity in the source) in each cell is calculated using microdosimetry approach and the proposed formulation of MIRD committee. Results: A comparison of the values obtained for the source cell with the corresponding MIRD values indicates a good agreement, which implies the high ability of Geant4-DNA in microdosimetry simulations. The evaluation of the results suggests that a large part of the energy emitted within the source cell is deposited in the cell itself, which is lowered by increasing energy so that for the energy of 20 keV, it reaches less than 50%. Also, the cell that is far from the source cell (compared to other cells) has a lower energy deposition and S-value. Conclusion: From the assessment of the calculated values and their comparison with each other, it is understood that the less the energy of the primary electron is, the less energy is delivered to the adjacent healthy cells. Due to the very low threshold excitation of liquid water (7.4 eV) which is the main compartment of the cells, this is meant to reduce the risk of damage to adjacent healthy cells. Of course, the electron energy should not be so low that reduces its fatality for cancer cells and thus the efficacy of treatment. Therefore, attention to the mentioned cases, as well as the dimensions of the cell studied and its distance with adjacent cells, is crucial for the selection of an efficient electron-emitter radionuclide.

OA167] Development of a realistic geometry model for cellular dosimetry of different therapeutic isotopes used in internal radiotherapy

Purpose This study is conducted to improve the multi-cellular model which would simulate an in-vitro scenario and to estimate the absorbed dose at the cellular and subcellular level for different therapeutic isotopes used in internal radiotherapy such as I-131, Y-90 and Lu-177. The objective of this study is to develop a complex model of a multicellular cell-cluster. Methods S-factors (absorbed dose per unit cumulated activity) calculations using Monte Carlo simulations were performed by using Monte Carlo N-Particle eXtended (MCNPX) code. S-cross (cross-dose) minimum, S-cross maximum and S-self (self-dose) were calculated. S-cross mean values were provided by using the Medical Internal Radiation Dose (MIRD) cell2 software. Nucleus (N), cytoplasm (Cy), cell surface (CS) and three isotopes, Y-90, I-131 and Lu-177 used for internal radiotherapy were simulated. Python software was used to generate random coordinates of cells in order to build a complex model taking into account realistic conditions (cell size, cluster size). The calculated coordinates of the cells are used as MCNPX input parameters. Results The coordinates of the cells are calculated and a multi-cellular model is developed. The comparison between MCNPX results and the MIRD cell2 values agreed well since the relative difference for S-self is less than 12% for the three radionuclides studied, Lu-177, I-131 and Y-90. The S-cross mean results provided by using MIRDcell2 software are between S-cross max and min data calculated for Lu-177, I-131 and Y-90 and for 3 configurations N to N; Cy to N and CS to N. The calculated ratios of S-cross vs S-self for three configurations (N to N, Cy to N, CS to N) are ranging from 10 to 50 for Lu-177, 20 to 70 for I-131 and from 40 to 140 for Y-90. It was showed that this ratio decreased for Lu-177 and I-131 with increasing the size of the cell and consequently the radius of the cell cluster. Conclusions The realistic geometry model provided by this study is designed to achieve as accurate results of estimating absorbed dose to the target cell and to predict the biological effect caused by the emitted radiations of therapeutic radionuclides.

Three-Dimensional Dosimetry for Radiation Safety Estimates from Intrathecal Administration.

Intrathecal administration is of growing interest for drug delivery, and its utility is being increasingly investigated through imaging. In this work, the 3-dimensional Voxel-Based Internal Dosimetry Application (VIDA) and 4D Extended Cardiac Torso Phantom (XCAT) were extended to provide radiation safety estimates specific to intrathecal administration. Methods: The 3-dimensional VIDA dosimetry application Monte Carlo simulation was run using a modified XCAT phantom with additional and edited cerebrospinal fluid (CSF) regions to produce voxel-level absorbed dose per unit cumulated activity maps for 9 selected source regions. Simulation validation was performed to compare absorbed dose estimates for common organs in a preexisting dosimetry tool (OLINDA/EXM). Dynamic planar imaging data were acquired in 6 healthy subjects using administered volumes of 5 or 15 mL (n = 3 each) of 185 MBq of 99mTc-diethylenetriaminepentaacetic acid. Absorbed dose was estimated for each subject using the intrathecal-specific dosimetry application. Results: Simulation results were within 6% of OLINDA estimates for common organs. Absorbed dose estimates were highest (0.3-0.8 mGy/MBq) in the lumbar CSF space. A whole-body effective dose estimate of 0.003 mSv/MBq was observed. An administered volume dependency was observed with a 15-mL volume, resulting in lower absorbed dose estimates for several intrathecal and nonintrathecal regions. Conclusion: The intrathecal-specific VIDA implementation enables tailored dosimetry estimation for regions most relevant in intrathecal administration. Absorbed doses are highly localized to CSF and spinal regions and should be taken into consideration when designing intrathecal imaging studies. A potentially interesting relationship was observed between absorbed dose and administered volume, which merits further investigation.

Absorbed dose evaluation of Auger electron-emitting radionuclides: impact of input decay spectra on dose point kernels and S-values

The aim of this study was to investigate the impact of decay data provided by the newly developed stochastic atomic relaxation model BrIccEmis on dose point kernels (DPKs - radial dose distribution around a unit point source) and S-values (absorbed dose per unit cumulated activity) of 14 Auger electron (AE) emitting radionuclides, namely 67Ga, 80mBr, 89Zr, 90Nb, 99mTc, 111In, 117mSn, 119Sb, 123I, 124I, 125I, 135La, 195mPt and 201Tl.Radiation spectra were based on the nuclear decay data from the medical internal radiation dose (MIRD) RADTABS program and the BrIccEmis code, assuming both an isolated-atom and condensed-phase approach. DPKs were simulated with the PENELOPE Monte Carlo (MC) code using event-by-event electron and photon transport. S-values for concentric spherical cells of various sizes were derived from these DPKs using appropriate geometric reduction factors.The number of Auger and Coster–Kronig (CK) electrons and x-ray photons released per nuclear decay (yield) from MIRD-RADTABS were consistently higher than those calculated using BrIccEmis. DPKs for the electron spectra from BrIccEmis were considerably different from MIRD-RADTABS in the first few hundred nanometres from a point source where most of the Auger electrons are stopped. S-values were, however, not significantly impacted as the differences in DPKs in the sub-micrometre dimension were quickly diminished in larger dimensions.Overestimation in the total AE energy output by MIRD-RADTABS leads to higher predicted energy deposition by AE emitting radionuclides, especially in the immediate vicinity of the decaying radionuclides. This should be taken into account when MIRD-RADTABS data are used to simulate biological damage at nanoscale dimensions.

Cellular and subcellular dosimetry of radioisotopes used for pet imaging

Introduction PET/CT imaging may be a useful method to follow and monitor the homing of hematopoietic stem and progenitor cells (HSPC) after HSPC injection in mice. To improve the method of HSPC radiolabelling and to select the best radioisotopes for this technique a cellular dosimetry is required. Purpose This early research work is focused on using Monte Carlo code to estimate the dose at cellular and subcellular levels for 3 radioisotopes used in PET: F-18, Cu-64 and Zr-89. Methods S-values (absorbed dose per unit cumulated activity) calculations using Monte Carlo (MC) simulations are carried out, nucleus (N), Cytoplasm (Cy), Cellular surface (CS) and radiation source were simulated. The cells are assumed to be spherical with the radii of the cell and cell nucleus ranging from 4 to 8 μm. Different source-to-target combinations are considered namely nucleus to nucleus (N ← N), cytoplasm-to-nucleus (N ← Cy) and cell surface-to-nucleus (N ← CS). The S-values (in Gy/Bq.s) were calculated for cell nucleus and cellular surface distribution of radioactivity. Results A comparison of MC results with the MIRD values for studied configurations are carried out for the radioisotopes studied. We generally find the largest deviations with MIRD for geometries where the target is at some distance from the source and, therefore, the results depend more strongly upon the plasmic membrane penetration ability of particles.

Dosimetry methodology for diagnostic nuclear medicine

For diagnostic dosimetry in nuclear medicine, quantitative imaging and activity measurements of blood and urine samples are essential. This is followed by the calculation of the absorbed organ doses and the effective dose. To achieve this, a correct temporal sampling and the use of adequate procedures to integrate the time-activity curves to obtain the total number of decays in the source organs (the time-integrated activity coefficients, TIACs) are prerequisites. If the TIACs are known, a calculation of the absorbed doses is performed by applying the “MIRD formalism”: D = TIAC · A 0 · S D: the mean absorbed dose to a target from a source region. A 0 : administered activity S: mean absorbed dose per unit cumulated activity in the target region. The S-values used for diagnostics are still based on mathematical phantoms. Although, the ICRP in its publication 103 requires the use of a set of gender-specific realistic voxel phantoms, the S-values for isotopes, however, are not yet made publicly available. For diagnostics the effective dose is the main protection quantity. It is calculated using the tissue weighting factors established by the ICRP in the publications ICRP60 and ICRP103. The effective dose, however, is only intended to calculate the risk for an age-independent reference person, not the individual risk. It is a protection quantity and is related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation.

Cellular dosimetry calculations for Strontium-90 using Monte Carlo code PENELOPE

Purpose: To improve risk assessments associated with chronic exposure to Strontium-90 (Sr-90), for both the environment and human health, it is necessary to know the energy distribution in specific cells or tissue. Monte Carlo (MC) simulation codes are extremely useful tools for calculating deposition energy. The present work was focused on the validation of the MC code PENetration and Energy LOss of Positrons and Electrons (PENELOPE) and the assessment of dose distribution to bone marrow cells from punctual Sr-90 source localized within the cortical bone part.Materials and methods: S-values (absorbed dose per unit cumulated activity) calculations using Monte Carlo simulations were performed by using PENELOPE and Monte Carlo N-Particle eXtended (MCNPX). Cytoplasm, nucleus, cell surface, mouse femur bone and Sr-90 radiation source were simulated. Cells are assumed to be spherical with the radii of the cell and cell nucleus ranging from 2–10 μm. The Sr-90 source is assumed to be uniformly distributed in cell nucleus, cytoplasm and cell surface.Results: The comparison of S-values calculated with PENELOPE to MCNPX results and the Medical Internal Radiation Dose (MIRD) values agreed very well since the relative deviations were less than 4.5%. The dose distribution to mouse bone marrow cells showed that the cells localized near the cortical part received the maximum dose.Conclusion: The MC code PENELOPE may prove useful for cellular dosimetry involving radiation transport through materials other than water, or for complex distributions of radionuclides and geometries.

Dose per unit cumulated activity (S-values) for e− and beta emitting radionuclides in cancer cell models calculated by Monte Carlo simulation

Cell dosimetry is relevant regarding new efforts in specific molecular radiotherapy using Auger, CE and beta emitters. Absorbed dose in cells can be obtained by means of the dose per unit cumulated activity (S-values), together with the activity distribution. In this work, Monte Carlo simulation codes PENELOPE and MCNPX were used to obtain cellular S-values for point and extended sources of electrons and beta emitting radionuclides in the nucleus of breast (MDA-MB231, MCF7) and prostate (PC3) cancer cell models.

Fast Monte Carlo simulation of DNA damage induction by Auger-electron emission

Purpose: A local damage model (LDM) was developed to estimate the biological efficiency of Auger-electron-emitting radionuclides.Materials and methods: The LDM required information on the local dose distribution, local energy spectrum, and clustered DNA damage yields in the cell nucleus. To apply the model, the nucleus was divided into concentric shells where each shell contributed its own local dose, energy spectrum, and damage yield. The local doses and energy spectra were computed using the PENELOPE (PENetration and Energy LOss of Positrons and Electrons) code. The DNA damage yields were estimated using the MCDS (Monte Carlo damage simulation) code.Results: For a typical 4-μm radius mammalian cell nucleus, the absorbed doses to the cell nucleus per unit cumulated activity, equal to 0.0065, 0.00418, 0.0028, 0.0027 and 0.0015 Gy Bq−1 s−1 for 125I, 119Sb, 123I, 111In and 99mTc, were within 6% difference with the MIRD (Medical Internal Radiation Dose) published data. The simulated total (simple and complex) single-strand break (SSB) and double-strand break (DSB) yields were in the same order, i.e., 125I > 119Sb > 123I > 111In > 99mTc. The agreement between present results and literature data for the DNA damage yields was generally good. More than 75% of the total SSB and DSB yields were contributed from regions within 2.5 μm of the nucleus center.Conclusions: The proposed methodology was computationally efficient and could be applied to other irradiation geometries such as cell clusters.

Cellular dosimetry of strontium-90 using the Monte Carlo code MCNPX, detection and X-ray microanalysis

The aim of this study is to provide data that increase knowledge about the possible health effects of exposure to 90 Sr contaminant in drinking water. 90 Sr detection in the mouse bone model plays an important complementary role with computational dosimetry in these investigations. S-value (absorbed dose per unit cumulated activity) calculations using Monte Carlo (MC) simulations, 90 Sr detection by liquid scintillation β counting in the femur bone and X-ray microanalysis were carried out. The present work is focused on using MCNPX and its validation at a cellular level. The cytoplasm (Cy), nucleus (N) and 90 Sr radiation source were simulated with the MC code MCNPX. Cells are assumed to be spherical, with the radii of the cell and cell nucleus ranging from 2 to 10 μm. The S-value (in Gy/Bq.s) calculations were provided for a 90 Sr source distributed uniformly in the cell nucleus or cytoplasm and for two source- target combinations (t←s). A comparison between the calculated MC results and the MIRD values agreed very well since the relative deviations are less than 4%. The earliest results of X-ray microanalysis indicated that the 90 Sr was below the detection limit (<0.1%) in the bone tissue. However, the measurements by liquid scintillation showed the presence of 90 Sr in the femur bone.

Biological Tissue Modeling with Agar Gel Phantom for Radiation Dosimetry of &amp;lt;sup&amp;gt;99m&amp;lt;/sup&amp;gt;Tc

The biological tissue has been mimicked and replaced by other materials, which have shown certain radiological similarity determined by attenuation coefficient (μ), density and atomic number. Specifically, in molecular imaging and radiation therapy have been developed multifunctional radiopharmaceuticals which contain beta/gamma and/or light emitters to chronic degenerative diseases treatment. Therefore, it is necessary to develop phantoms that allow optical and radiometric characterization. Since the agar gel has shown to be a medium which allows to model biological tissue in phototherapy studies, the aim of this study is to determine whether the agar gel may be used as biological tissue substitutes in 99mTc dosimetry. Agar gel was prepared to 1% and 2.3% (water:agar) and its radiologicalproperties as: linear attenuation coefficient obtained by narrow beam geometry and XCOM software, density and effective atomic number (Zeff) were determined. Using the determined μ, photontransmission was calculated by Monte Carlosimulation. The 99mTc source region was immersed in a water phantom, two source regions were used, one source region was filled with water and another with agar gel. For both cases; the cumulated activity () by conjugate view method, the absorbed doseper unitcumulated activity (S) and absorbed dose (D) were determined. The 2.3% concentration gel consistency facilitated its handling during a bigger irradiation time. A was obtained and also this value was corroborated with the XCOM software. The agar gel density was and . The calculated cumulated activity presented 1% difference in both phantoms. The absorbed doseper unitcumulated activity was the same in both media, therefore the D too. Agar gel showed to be equivalent to water in terms of radiological properties for 140 keV photons, thus it can substitute soft tissue in 99mTc dosimetry.

3D calculation of absorbed dose for 131I-targeted radiotherapy: a Monte Carlo study

Various methods, such as those developed by the Medical Internal Radiation Dosimetry (MIRD) Committee of the Society of Nuclear Medicine or employing dose point kernels, have been applied to the radiation dosimetry of (131)I radionuclide therapy. However, studies have not shown a strong relationship between tumour absorbed dose and its overall therapeutic response, probably due in part to inaccuracies in activity and dose estimation. In the current study, the GATE Monte Carlo computer code was used to facilitate voxel-level radiation dosimetry for organ activities measured in an (131)I-treated thyroid cancer patient. This approach allows incorporation of the size, shape and composition of organs (in the current study, in the Zubal anthropomorphic phantom) and intra-organ and intra-tumour inhomogeneities in the activity distributions. The total activities of the tumours and their heterogeneous distributions were measured from the SPECT images to calculate the dose maps. For investigating the effect of activity distribution on dose distribution, a hypothetical homogeneous distribution of the same total activity was considered in the tumours. It was observed that the tumour mean absorbed dose rates per unit cumulated activity were 0.65E-5 and 0.61E-5 mGY MBq(-1) s(-1) for the uniform and non-uniform distributions in the tumour, respectively, which do not differ considerably. However, the dose-volume histograms (DVH) show that the tumour non-uniform activity distribution decreases the absorbed dose to portions of the tumour volume. In such a case, it can be misleading to quote the mean or maximum absorbed dose, because overall response is likely limited by the tumour volume that receives low (i.e. non-cytocidal) doses. Three-dimensional radiation dosimetry, and calculation of tumour DVHs, may lead to the derivation of clinically reliable dose-response relationships and therefore may ultimately improve treatment planning as well as response assessment for radionuclide therapy.

Geometric models in dosimetry of thyroid remnant mass

Absorbed dose to thyroid remnant tissue after 131I ablation becomes mass/size-dependent. This is a direct consequence of the small remnant size and radiation escape starts to be relevant. The self-absorbed fraction becomes mass/size-dependent. We have used Monte Carlo simulations to investigate the influence of the thyroid remnant shape upon the absorbed fraction calculation. Thyroid residue was modeled using spherical, cylindrical and elliptical shapes. Uniform beta activity distribution and unit density medium (water) within a remnant was assumed. For each of the geometrical models beta self-absorbed fraction (varphi(beta)) was calculated using Monte Carlo codes, while the mean absorbed dose per unit cumulated activity (S(beta)) was calculated using MIRD formalism. For spherical objects varphi(mono) for mean beta energy (E = 0.182 MeV) of 131I is always greater than varphi(beta) calculated for the complete beta spectrum. For spheres having diameters 2-6 mm and assumption varphi(beta) = 1, S(beta) is over-estimated by 11-37%. For cylinder and prolate spheroid of the same length and thickness, S(beta) for cylinder is 30% smaller because of the greater mass. Similarly, elliptical cylinder and general ellipsoid of the same length and the same perpendicular dimensions (width and breadth), have similar varphi(beta), while S(beta) for elliptical cylinder is correspondingly smaller. For accurate dosimetry of thyroid remnants having masses <1 g and chordal lengths <1 cm it is necessary to calculate varphi(beta) for the full beta spectrum, or S(beta) will be overestimated. The shape of the remnant may also be important since elongated non-spherical objects may also have varphi(beta) < 1.

Evaluation of self-dose S values for positron emitters in voxel phantoms

In recent years, concern has been raised about patient-specific doses due to the increased use of PET imaging. It is of scientific and practical interest for the accurate quantification of the doses to patients administered a radiopharmaceutical for PET imaging. In the present study, Monte Carlo simulations have been carried out to evaluate S values--the mean absorbed dose to the target region per unit cumulated activity in the source region--for positron emitters in the brain, heart and the urinary bladder content. The positron emitters considered were four radionuclides that are frequently used for PET imaging: 11C, 13N, 15O and 18F. S values were evaluated for the Medical Internal Radiation Dose 5 type mathematical phantom and the adult voxel phantoms developed at the Japan Atomic Energy Research Institute (JAERI). Consequently, Monte Carlo simulation and voxel phantoms were found to be useful in the evaluation of the beta dose to organs, in particular to hollow organs such as the urinary bladder. It was also demonstrated that the self-dose S values largely depend on the beta-ray energy and the mass of each target region.

A Comparison of High- Versus Low-Linear Energy Transfer Somatostatin Receptor Targeted Radionuclide Therapy In Vitro

The somatostatin analog [DOTA(0)-Tyr(3)]-octreotide (DOTATOC) has been widely used to target somatostatin receptor expressing tumors for therapy using radionuclides such as (90)Y or (177)Lu. This aim of this study was to compare the effects of DOTATOC labeled to high linear energy transfer (LET) alpha-emitter (213)Bi and low-LET beta-emitter (177)Lu in vitro. Somatostatin receptor (sstr)-positive cell line Capan-2 and sstr-negative control cell line A549 were used for the experiments. The effects of two exposure times using different radiation doses of high-LET alpha-emitter (213)Bi and low-LET beta-emitter (177)Lu were investigated using cell survival assay. The apoptotic effects were investigated using Cell Death Detection ELISA(PLUS)10x. The cumulated activity and the mean absorbed dose per unit cumulated activity were calculated using MIRD cellular Svalues. (213)Bi-DOTATOC had an approximately four times greater induction of apoptosis than (177)Lu-DOTATOC and a 100 times greater induction of apoptosis than nonradiolabeled DOTATOC. Nonspecific radiolabeled tetra-azacyclododecanetetra-acetic acid (DOTA) had a less pronounced effect on the cell survival and apoptosis, as compared to the sstr-specific radiolabeled DOTATOC. (213)Bi-DOTATOC is significantly more potent than (177)Lu-DOTATOC in vitro because of its high-LET alpha-emission.(213)Bi-DOTATOC shows enhanced effects on mitotic and apoptotic cell deaths.

The Need for Better Methods to Determine Release Criteria for Patients Administered Radioactive Material

In current NRC regulations, three options exist that may be used to determine release criteria for patients administered radioactive materials. Absorbed dose estimates may be based on administered activity, measured dose rate, or on patient-specific calculations. All of these methods proposed by the NRC can lead to overestimation of the dose equivalent to others due to their oversimplified nature. The primary oversimplifications are the use of a point source methodology and using the measured surface entrance dose rate to determine whole body dose. In order to show the inaccuracy of these oversimplifications for 131I, results using Monte Carlo radiation transport analysis with simplified anthropomorphic mathematical phantoms were determined. These results were then compared to actual patient measurements and the results of point source analysis. The measurement data were taken from 49 131I radioimmunotherapy patients. The point source calculations were performed using well established methodologies and using the same assumptions as in the NRC regulations for patient release criteria. Monte Carlo results were obtained by implementing two simplified 70 kg anthropomorphic phantoms and performing radiation transport simulation. The activity in the "patient" phantom was assumed to be localized in the abdominal region to correspond to the activity localization seen in the radioimmunotherapy patients who were measured. Dose equivalents per unit cumulated activities were determined for 131I using the various methods. The relationship between measured dose equivalent per unit cumulated activity and whole body dose equivalent per unit cumulated activity was also investigated using Monte Carlo analysis. The point source method as implemented by the NRC yields an estimated dose equivalent per unit cumulated activity of 1.6 x 10(-8) mSv MBq(-1) s(-1) at 1 m (2.2 x 10(-4) rem mCi(-1) h(-1) at 1 m), and the Monte Carlo based method yielded a whole body dose equivalent per unit cumulated activity in the target phantom of 6.8 x 10(-9) mSv MBq(-1) s(-1)(9.0 x 10(-5) rem mCi(-1) h(-1)) for abdominal localization of activity in the source phantom. The measurements of the radioimmunotherapy patients yielded an average result of 1.0 x 10(-8) mSv MBq(-1) s(-1) (13 x 10(-4) rem mCi(-1) h(-1)). When corrected for the difference between measured surface dose equivalent and whole body dose equivalent as determined by Monte Carlo analysis, these measurements represent a whole body dose equivalent per unit cumulated activity of about 6.2 x 10(-9) mSv MBq(-1) s(-1) (8.1 x 10(-5) rem mCi(-1) h(-1)). Based on these results, the current NRC dose-based methodology for the release of patients administered radioactive materials significantly overestimates the dose equivalent to others from 131I therapy patients.

Calculation of equivalent dose for Auger electron emitting radionuclides distributed in human organs.

Radionuclides that emit Auger electrons can be extremely radiotoxic depending on the subcellular distribution of the radiochemical. Despite this, ICRP 60 provides no guidance in the calculation of equivalent dose H(T) for Auger electrons. The recent report by the American Association of Physicists in Medicine recommends a radiation weighting factor wR of 20 for stochastic effects caused by Auger electrons, along with a method of calculating the equivalent dose that takes into account the subcellular distribution of the radionuclide. In view of these recommendations, it is important to reevaluate equivalent doses from Auger electron emitters. The mean absorbed dose per unit cumulated activity (S-value) from Auger electrons and other radiations is calculated for ninety Auger-electron-emitting radionuclides distributed in human ovaries, testes and liver. Using these S-values, and the formalism given in the recent AAPM report, the dependence of the organ equivalent doses on subcellular distribution of the Auger electron emitters is examined. The results show an increase in the mean equivalent dose for Auger electron emitters when a significant fraction of the organ activity localizes in the DNA.