Monte Carlo estimates of absorbed dose rate in various tissues and organs

A computer program based on the Monte Carlo technique was developed for calculation of absorbed dose rate in various tissues and organs. The accuracy of the program was tested by reproducing Berger's values of the specific absorbed fractions for point isotropic sources in water, and a good agreement with those obtained by the moments method was found within an error of several percent. In comparing with experiment and other Monte Carlo results, good agreement was also obtained within the range of statistical error. The absorbed dose rate for an 123I, 124I, 125I, 126I and 99mTc point source and their specific dose constants in various tissues and organs were calculated using this program. This computer program has the mass energy absorption and attenuation coefficients for 69 tissues and organs as a database file, and can be extended to various radionuclides used in nuclear medicine by adding their nuclear data to the program.     

Monte Carlo estimates of absorbed dose rate in various tissues and organs

A computer program based on the Monte Carlo technique was developed for calculation of absorbed dose rate in various tissues and organs. The accuracy of the program was tested by reproducing Berger's values of the specific absorbed fractions for point isotropic sources in water, and a good agreement with those obtained by the moments method was found within an error of several percent. In comparing with experiment and other Monte Carlo results, good agreement was also obtained within the range of statistical error. The absorbed dose rate for an ¹²³I, ¹²⁴I, ¹²⁵I, ¹²⁶I and ^99mTc point source and their specific dose constants in various tissues and organs were calculated using this program. This computer program has the mass energy absorption and attenuation coefficients for 69 tissues and organs as a database file, and can be extended to various radionuclides used in nuclear medicine by adding their nuclear data to the program.     

Estimates of beta absorbed fractions in small tissue volumes for selected radionuclides

Energy deposition patterns are dependent upon the size and geometry of the source region, distribution of radioactive material, types of radiations and energies emitted by the radionuclide, as well as interfaces between different materials which may exist within the region. Commonly, in absorbed dose calculations for internally deposited beta-emitting radionuclides, it is assumed that the absorbed fraction of energy for the mean beta energy is a sufficient representation of the beta spectrum. The accuracy of this assumption was tested by comparing absorbed fractions calculated using actual beta spectral energies with those obtained using the mean beta energy for several radionuclides commonly used in nuclear medicine. A sphere composed of tissue was chosen as the preferred geometry. Spheres of 0.1, 0.5, 1.0, and 2.0 cm radius were used, and absorbed fractions were calculated as a function of surface-to-volume ratios. This allows the assessment of absorbed fraction in spheres where there is a uniform distribution of a radionuclide.     

Five pediatric head and brain mathematical models for use in internal dosimetry.

Mathematical models of the head and brain currently used in pediatric neuroimaging dosimetry lack the anatomic detail needed to provide the necessary physical data for suborgan brain dosimetry. To overcome this limitation, the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine recently adopted a detailed dosimetric model of the head and brain for the adult. METHODS: New head and brain models have been developed for a newborn, 1, 5, 10 and 15 y old for use in internal dosimetry. These models are based on the MIRD adult head and brain model and on published head and brain dimensions. They contain the same eight brain subregions and the same head regions as the adult model. These new models were coupled with the Monte Carlo transport code EGS4, and absorbed fractions of energy were calculated for 14 sources of monoenergetic photons and electrons in the energy range of 10 keV-4 MeV. These absorbed fractions were then used along with radionuclide decay data to generate S values for all ages for 99mTc, considering 12 source and 15 target regions. RESULTS: Explicit transport of positrons was also considered with separation of the annihilation photons component to the absorbed fraction of energy in the calculation of S values for positron-emitting radionuclides. No statistically significant differences were found when S values were calculated for positron-emitting radionuclides under explicit consideration of the annihilation event compared with the traditional assumption of a uniform distribution of 0.511-MeV photons. CONCLUSION: The need for electron transport within the suborgan brain regions of these pediatric phantoms was reflected by the relatively fast decrease of the self-absorbed fraction within many of the brain subregions, with increasing particle energy. This series of five dosimetric head and brain models will allow more precise dosimetry of radiopharmaceuticals in pediatric nuclear medicine brain procedures.     

Natural radioactivity and gamma dose from Sri Lankan clay bricks used in building construction.

The specific radioactivity concentrations of 226Ra, 232Th and 40K have been determined by gamma ray spectrometry with an HPGe detector in clay brick samples from kiln sites located in 17 towns. The average values of the measured activities are 35, 72, and 585 Bq kg(-1), respectively, for the above radionuclides. The average estimated radium equivalent concentration is 183 Bq kg(-1) and is comparable with reported values for many countries in the world. This value and the value obtained from the criteria formula suggest that the use of local clay bricks do not pose a radiological hazard. The calculated average absorbed dose rate in air within buildings was found to be 102 nGy h(-1) while the population weighted indoor annual effective dose was 0.20 mSv.     

MIRD Pamphlet No 19: absorbed fractions and radionuclide S values for six age-dependent multiregion models of the kidney.

As one of the major organs of the excretory pathway, the kidneys represent a frequent source of radiopharmaceutical uptake in both diagnostic and therapeutic nuclear medicine. The unique organization of the functional tissues of the organ ensures transient changes in suborgan localization of renal activity. Current single-region dosimetric models of the kidneys, however, force the assumption of a uniform distribution of radioactivity across the entire organ. The average absorbed dose to the kidneys predicted by such models can misrepresent local regional doses to specific substructures. METHODS: To facilitate suborgan dosimetry for the kidneys, 6 new age-dependent multiregion kidney models are presented. The outer dimensions of the models conform to those used currently in single-region kidney models, whereas interior structures are defined for the renal cortex, the medullary pyramids with papillae (2 vertical and 3 horizontal), and the renal pelvis. Absorbed fractions of energy were calculated for both photon and electron sources (10 keV to 4 MeV) located in each source region within the 6 age-dependent models. The absorbed fractions were then used to assemble S values for radionuclides of potential interest in suborgan kidney dosimetry. RESULTS: For the adult, the absorbed dose to the renal cortex for (90)Y-labeled compounds retained within that subregion is approximately 1.3 times that predicted by the single-region kidney model, whereas the medullary dose is only 26% of that same single-region value. For compounds that are rapidly filtered in the kidneys, the renal cortex dose is approximately one-half of that predicted under the single-region model, whereas the tissues of the medullary pyramids receive an absorbed dose 1.5-1.8 times larger. CONCLUSION: The multiregion model described here permits estimates of regional kidney dose not previously supported by current single-region models. Full utilization of the new model, however, requires serial imaging of the kidneys with regions of interest assigned to the renal cortex and medulla.     

俄歇电子发射核素靶向治疗中细胞平均吸收剂量的计算

目的 给出一种新的方法,计算俄歇电子发射核素在细胞中均匀分布和非均匀分布时细胞和细胞核的平均吸收剂量以吸引剂量在细胞内的分布。方法 俄歇电子单位路径的能量损失用多项式拟合,用解析方法给出点源在细胞或细胞核内的能量沉积,从而得到不同源－靶组合的S值。放射性核素在细胞中径向线性分布和指数分布,分别计算了细胞和细胞核的平均吸收剂量;以及放射源距细胞中心不同距离时对细胞吸收剂量的影响。光子对细胞或细胞核的剂量贡献忽略不计。结果 平均吸收剂量及其在细胞内的分布和细胞的大小、俄歇电子能谱、核素的空间分布密切相关。细胞核内的核素对细胞核吸收剂量的贡献远大于细胞质中的核素。结论 俄歇电子在生物组织中的射程短,单位路径的能量损失高,能产生非常高的局部能量沉积。我们给出的细胞平均吸收剂量的解析计算方法计算速度快,结果可靠。     

基于排泄物的γ能谱分析估算放射性核素摄入量及待积有效剂量

目的 建立一种基于γ能谱分析的放射性核素摄入量和待积有效剂量估算方法。方法 利用γ能谱系统测量放射性内污染人员的排泄物（粪、尿）中放射性核素活度，根据测量其结果估算核素摄人量和待积有效剂量。并作软件化设计以提高计算速度和准确程度。结果 该方法能够对放射性内污染人员进行离体活度测量和剂量估算，软件化设计提供快速准确的保证。结论 该研究提供了一种快速测量和评价放射性核素内污染的方法，能够满足应急情况下的测量需求。     

Cellular dose conversion factors for alpha-particle--emitting radionuclides of interest in radionuclide therapy.

alpha-Particle--emitting radionuclides are of increasing interest in radionuclide therapy. The decay scheme of alpha-emitting radionuclides typically includes a chain of unstable progeny. It is generally assumed that alpha-particle emission by the parent radionuclide will break the chemical bond with its carrier molecule and that the resulting daughter atom will no longer be associated with the carrier molecule. If the daughter is very short lived, it will not have enough time to be carried any significant distance from the site of parent decay and a cellular, absorbed dose estimate must consider the energy deposited by the daughter as well as the parent. Depending on the site of parent decay and the expected removal rate of daughter atoms from this site, the contribution of emissions from longer-lived daughters may also be warranted. In this study, dose conversion factors (DCFs) for cellular dimensions that incorporate the fate of daughter radionuclides were derived for (225)Ac, (213)Bi, (211)At, and (223)Ra, the alpha-particle--emitting radionuclides of interest in radionuclide therapy. METHODS: The dose contribution of daughter radionuclides at the site of parent decay was made dependent on a cutoff time parameter, which was used to estimate the fraction of daughter decays expected at the site of parent decay. Previously tabulated S values (cell-surface to nucleus and cell-surface to cell) for each daughter in the decay scheme were scaled by this fraction and a sum over all daughters was performed to yield a cutoff time--dependent set of corresponding DCF values for each radionuclide. RESULTS: DCF values for the absorbed dose to the nuclear or cellular volume from cell-surface decays are presented as a function of the cutoff time for 4 different cellular and nuclear dimensions. CONCLUSION: In contrast to the cellular S values that account only for parent decay, the DCF values provided in this study make it possible to easily include the contribution of daughter decays in cellular alpha-particle emitter dose calculations.     

Half-life measurements at the National Institute of Standards and Technology.

For nearly half a century the half-lives of many radionuclides have been measured with increasing precision. The results of these measurements for many long-lived radionuclides, such as 60Co, 137Cs, 85Kr, 133Ba, 207Bi, 152Eu, 154Eu, and 155Eu, have been updated recently by the Radioactivity Group of NIST. These long-lived radionuclides are used extensively to calibrate various nuclear counting and monitoring systems. The long-term precision of these calibrations can be greatly affected by the uncertainties in the calibrant half-lives. Results for the half-lives of many radionuclides measured over the last four decades are tabulated. In addition, values of the half-lives of several short-lived radionuclides used in nuclear medicine are addressed, which are critical in determining the correct dosage given in patient treatment, are addressed. Comparisons with the recommended values from the International Atomic Energy Agency Coordinated Research Program and the Evaluated Nuclear Structure Data File from Brookhaven National Laboratory are presented and any apparent disagreements noted.     

MIRD pamphlet No. 20: the effect of model assumptions on kidney dosimetry and response--implications for radionuclide therapy

Renal toxicity associated with small-molecule radionuclide therapy has been shown to be dose-limiting for many clinical studies. Strategies for maximizing dose to the target tissues while sparing normal critical organs based on absorbed dose and biologic response parameters are commonly used in external-beam therapy. However, radiopharmaceuticals passing though the kidneys result in a differential dose rate to suborgan elements, presenting a significant challenge in assessing an accurate dose-response relationship that is predictive of toxicity in future patients. We have modeled the multiregional internal dosimetry of the kidneys combined with the biologic response parameters based on experience with brachytherapy and external-beam radiation therapy to provide an approach for predicting radiation toxicity to the kidneys. METHODS: The multiregion kidney dosimetry model of MIRD pamphlet no. 19 has been used to calculate absorbed dose to regional structures based on preclinical and clinical data. Using the linear quadratic model for radiobiologic response, we computed regionally based surviving fractions for the kidney cortex and medulla in terms of their concentration ratios for several examples of radiopharmaceutical uptake and clearance. We used past experience to illustrate the relationship between absorbed dose and calculated biologically effective dose (BED) with radionuclide-induced nephrotoxicity. RESULTS: Parametric analysis for the examples showed that high dose rates associated with regions of high activity concentration resulted in the greatest decrease in tissue survival. Higher dose rates from short-lived radionuclides or increased localization of radiopharmaceuticals in radiosensitive kidney subregions can potentially lead to greater whole-organ toxicity. This finding is consistent with reports of kidney toxicity associated with early peptide receptor radionuclide therapy and (166)Ho-phosphonate clinical investigations. CONCLUSION: Radionuclide therapy dose-response data, when expressed in terms of biologically effective dose, have been found to be consistent with external-beam experience for predicting kidney toxicity. Model predictions using both the multiregion kidney and linear quadratic models may serve to guide the investigator in planning and optimizing future clinical trials of radionuclide therapy.     

Evaluation of parameters influencing S values in mouse dosimetry.

Clinical radionuclide therapy studies are commonly preceded by studies with small animals. Reliable evaluation of therapeutic efficacy must be based on accurate dosimetry. This study was performed to evaluate the influence of the mass of organs, the shape of organs, and the distances between organs on S values for mice. METHODS: A voxel-based version of a geometric model of a mouse was developed for input in our Monte Carlo program based on EGS4. Simulations were made for each source organ separately to resolve the S values for each organ. For verification purposes, S values were calculated for spheres of different masses and compared with the S values in the MIRDOSE3.1 software and with the S values on the Radiation Dose Assessment Resource Web site. The variation in the mass of the organs was determined from dissected mice. The influence of the shape of an organ was investigated by successive elongation of a sphere into spheroids with a constant mass. The right kidney was moved in the phantom of the mouse to evaluate the effect of organ distances on S values. The absorbed fractions for the mouse model presented here were compared with the results from some previously published models. The radionuclides used were (90)Y, (131)I, (111)In, and (99m)Tc. RESULTS: The results showed that the organ mass for one animal can differ by up to 33% from the mean mass. If linear interpolation from S value tables is used to obtain an S value for the specific mass of an organ, then the S value can differ by up to 80% from its true value. The corresponding deviation obtained by scaling according to mass is 20%. The shape of an organ was found to be the least important parameter for the S value. The cross-absorbed S value is strongly dependent on the geometry and the emitted radiation. For example, a 9.2-mm movement of the kidney can cause the S value from the liver to the right kidney to decrease to 0.05% of its original value for (90)Y. CONCLUSION: We conclude that the mass and the shape of organs and their locations relative to each other have considerable effects on mouse dosimetry.     

Analytical functions for beta and gamma absorbed fractions of iodine-131 in spherical and ellipsoidal volumes

Background

The beta and gamma absorbed fractions in organs and tissues are the important key factors of radionuclide internal dosimetry based on Medical Internal Radiation Dose (MIRD) approach.

Objectives

The aim of this study is to find suitable analytical functions for beta and gamma absorbed fractions in spherical and ellipsoidal volumes with a uniform distribution of iodine-131 radionuclide.

Methods

MCNPX code has been used to calculate the energy absorption from beta and gamma rays of iodine-131 uniformly distributed inside different ellipsoids and spheres, and then the absorbed fractions have been evaluated.

Results

We have found the fit parameters of a suitable analytical function for the beta absorbed fraction, depending on a generalized radius for ellipsoid based on the radius of sphere, and a linear fit function for the gamma absorbed fraction.

Conclusion

The analytical functions that we obtained from fitting process in Monte Carlo data can be used for obtaining the absorbed fractions of iodine-131 beta and gamma rays for any volume of the thyroid lobe. Moreover, our results for the spheres are in good agreement with the results of MIRD and other scientific literatures.     

Radiation dose distributions in normal tissue adjacent to tumors containing (131)I or (90)Y: the potential for toxicity.

Given the relatively large tumor-absorbed doses reported for patients receiving radionuclide therapy, particularly radioimmunotherapy, and the relatively long pathlength of the nonpenetrating emissions of some radionuclides being used for these therapies, there exists the possibility of large absorbed doses to tissues adjacent to, surrounded by, or surrounding these tumors. Because tumors can occur adjacent to critical organs or tissues, such as arteries, nerves, pericardium, and the walls of the organs of the gastrointestinal tract, large absorbed doses to these normal tissues can lead to acute complications. METHODS: In this study, the Monte Carlo radiation transport code MCNP4b was used to simulate the deposition of energy from emissions of 2 radionuclides of interest, (131)I and (90)Y, to assess the possible magnitude of the absorbed doses in tissues adjacent to tumors. Mathematic models were constructed to simulate situations that might occur, such as tumor wrapped around a small cylinder (e.g., a nerve or artery), tumor against a tissue (e.g., the pericardium or wall of any gastrointestinal tract organ), and tumor surrounded by any soft tissue. Tumor masses of 10, 20, and 40 g were used in each model. Depth dose distributions were calculated using Monte Carlo simulations of the radiation transport in these geometric models. RESULTS: For tissues close to tumors containing (90)Y, the absorbed dose ranged from 24% of the absorbed dose in the tumor, for the case of tissues 1 mm from the tumor, to 103% of the absorbed dose in the tumor, for the case of small structures such as nerves or arteries surrounded by tumor. For tissues close to tumors containing (131)I, the absorbed dose ranged from 4% of the absorbed dose in the tumor, for the case of tissues 1 mm from the tumor, to 46% of the absorbed dose in the tumor, for the case of small structures such as nerves or arteries surrounded by tumor. CONCLUSION: This study showed that when absorbed doses to tumors are large, the absorbed dose to adjacent tissues can also be large, potentially causing unexpected toxicities.     

Re-evaluation of absorbed fractions for photons and electrons in spheres of various sizes.

Absorbed fractions for unit density spheres in an infinite unit density medium, previously calculated for photon emitters and electron emitters, were reevaluated with the Monte Carlo codes EGS4 and MCNP4B. METHODS: Activity was assumed to be distributed uniformly throughout the spheres, and absorbed fractions for self-irradiation were calculated at discrete photon and electron energies. RESULTS: For electrons, the codes were in very good agreement with each other (+/-5%) and with published values, except at higher energies in the very smallest spheres, where some differences exceeded 10%. For photons, the codes were again in good agreement with each other but produced results that varied considerably from published MIRD values. For energies <1 MeV and sphere sizes <50 g, the absorbed fractions determined using the Monte Carlo codes were typically 20%-40% higher than values in MIRD 3 and 8. For energies >1 MeV, the Monte Carlo values were sometimes lower than those in the MIRD documents. Recommended values, generally the average results from the 2 Monte Carlo codes, are given for all sphere sizes and energies for both electrons and photons. CONCLUSION: The absorbed fractions calculated using the Monte Carlo codes should replace the older values and are helpful in evaluating tumor doses, doses to small organs, and other situations in which a uniform distribution of activity throughout a spherical structure of unit density can be assumed.     

Biologic dosimetry of bone marrow: induction of micronuclei in reticulocytes after exposure to 32P and 90Y.

Bone marrow is the dose-limiting organ in targeted radionuclide therapy. Hence, determination of the absorbed dose to bone marrow from incorporated radionuclides is a critical element in treatment planning. This study investigated the potential of the micronucleus assay in peripheral blood reticulocytes (MnRETs) as an in vivo biologic dosimeter for bone marrow. METHODS: After intravenous administration of 32P-orthophosphate or 90Y-citrate in Swiss Webster mice, DNA damage induced in bone marrow erythroblastoid cells was measured by subsequent scoring of MnRETs in peripheral blood. The response to exponentially decreasing dose rates was calibrated by irradiating animals with external 137Cs-gamma-rays. The gamma-ray dose rate was decreased exponentially, with the dose-rate decrease half-time corresponding to the effective clearance half-time (Te) of the radioactivity from the femoral bone (Te = 64 h for 90Y-citrate and Te = 255 h for 32P-orthophosphate). RESULTS: The maximum MnRETs frequency occurred on the second and third day after injection of 90Y-citrate and 32P-orthophosphate, respectively. The same pattern was observed for exponentially decreasing dose rates of 137Cs-gamma-rays. For each type of exposure, the maximum MnRETs frequency increased in a dose-dependent manner. Using the calibrated dosimeter, the initial dose rates to the marrow per unit of injected activity were 0.0020 cGy/h/kBq and 0.0026 cGy/h/kBq for 32P-orthophosphate and 90Y-citrate, respectively. CONCLUSION: Micronuclei in peripheral blood reticulocytes can be used as a noninvasive biologic dosimeter for measuring absorbed dose rate and absorbed dose to bone marrow from incorporated radionuclides.     

Towards absolute activity measurements by ionisation chambers using the PENELOPE Monte-Carlo code.

The Monte-Carlo code PENELOPE for Ionisation Chamber Simulation Method has been applied for the calculation of ionisation-chamber (IC) calibration factors. Measuring only a few radionuclides well selected within the relevant energy range, and determining an adjustable parameter, commonly used radionuclides can be measured without any specific calibration. The simulation revealed a discontinuity in the IC response as a function of photon energy and its dependence on the chemical composition of the radioactive solution.     

Effect of emaciation and obesity on small-animal internal radiation dosimetry for positron-emitting radionuclides

Purpose

Rats are widely used in biomedical research involving molecular imaging and therefore the radiation dose to animals has become a concern. The weight of laboratory animals might change through emaciation or obesity as a result of their use in various research experiments including those investigating different diet types. In this work, we evaluated the effects of changes in body weight induced by emaciation and obesity on the internal radiation dose from common positron-emitting radionuclides.

Methods

A systematic literature review was performed to determine normal anatomical parameters for adult rats and evaluate how organs change with variations in total body weight. The ROBY rat anatomical model was then modified to produce a normal adult rat, and mildly, moderately and severely emaciated and obese rats. Monte Carlo simulations were performed using MCNPX to estimate absorbed fractions, specific absorbed fractions (SAFs) and S-values for these models using different positron-emitting radionuclides. The results obtained for the different models were compared to corresponding estimates from the normal rat model.

Results

The SAFs and S-values for most source–target pairs between the various anatomical models were not significantly different, except where the intestine and the total body were considered as source regions. For the intestine, irradiating other organs in the obese model, the SAFs in organs in the anterior region of the splanchnocoele (e.g. kidney, liver and stomach) increased slightly, whereas the SAFs in organs in the posterior region of the splanchnocoele (e.g. bladder and testes) decreased owing to the increase in the distance separating the intestine and posterior abdominal organs because of the rat epididymal fat pad. For the total body, irradiating other organs, the SAFs and S-values were inversely related to body weight.

Conclusion

The effect of obesity on internal radiation dose is insignificant in most conditions for common positron-emitting radionuclides. Emaciation increases the cross-absorbed dose to organs from surrounding tissues, which might be a notable issue in laboratory animal internal dosimetry.     

A model-based method for the prediction of whole-body absorbed dose and bone marrow toxicity for <Superscript>186</Superscript>Re-HEDP treatment of skeletal metastases from prostate cancer

In high-activity rhenium-186 hydroxyethylidene diphosphonate ((186)Re-HEDP) treatment of bone metastatic disease from prostate cancer the dose-limiting factor is haematological toxicity. In this study, we examined the correlation of the injected activity and the whole-body absorbed dose with treatment toxicity and response. Since the best response is likely to be related to the maximum possible injected activity limited by the whole-body absorbed dose, the relationship between pre-therapy biochemical and physiological parameters and the whole-body absorbed dose was studied to derive an algorithm to predict the whole-body absorbed dose prior to injection of the radionuclide. The whole-body retention of radioactivity was measured at several time points after injection in a cohort of patients receiving activities ranging between 2,468 MBq and 5,497 MBq. The whole-body absorbed dose was calculated by fitting a sequential series of exponential phases to the whole-body time-activity data and by integrating this fit over time to obtain the whole-body cumulated activity. This was then converted to absorbed dose using the Medical Internal Radiation Dose (MIRD) committee methodology. Treatment toxicity was estimated by the relative decrease in white cell (WC) and platelet (Plt) counts after the injection of the radionuclide, and by their absolute nadir values. The criterion for a treatment response was a 50% or greater decrease in prostate-specific antigen (PSA) value lasting for 4 weeks. Alkaline phosphatase (AlkPh), chromium-51 ethylene diamine tetra-acetate ((51)Cr-EDTA) clearance rate and weight were measured before injection of the radionuclide. The whole-body absorbed dose showed a significant correlation with WC and Plt toxicity ( P=0.005 and 0.003 for the relative decrease and P=0.006 and 0.003 for the nadir values of WC and Plt counts respectively) in a multivariate analysis which included injected activity, whole-body absorbed dose, pre-treatment WC and Plt baseline counts, PSA and AlkPh values, and the pre-treatment Soloway score. The injected activity did not show any correlation with WC or Plt toxicity, but it did correlate with PSA response ( P=0.005). These results suggest that the administration of higher activities would be likely to generate a better response, but that the quantity of activity that can be administered is limited by the whole-body absorbed dose. We have derived and evaluated a model that estimates the whole-body absorbed dose on an individual patient basis prior to injection. This model uses the level of injected activity and pre-injection measurements of AlkPh, weight and (51)Cr-EDTA clearance. It gave good estimates of the whole-body absorbed dose, with an average difference between predicted and measured values of 15%. Furthermore, the whole-body absorbed dose predicted using this algorithm correlated with treatment toxicity. It could therefore be used to administer levels of activity on a patient-specific basis, which would help in the optimisation of targeted radionuclide therapy. We believe that algorithms of this kind, which use pre-injection biochemical and physiological measurements, could assist in the design of escalation trials based on a toxicity-limiting whole-body absorbed dose, rather than using the more conventional activity escalation approach.     

Absorbed dose estimates at the cellular level for I

Microdosimetric calculations of ¹³¹I have been evaluated for a single cell and for cell clusters. A VsBasic program has been used to calculate stopping power, linear energy transfer, range values and deposited energies per decay for beta particles, Auger and conversion electrons of ¹³¹I. The chemical composition of the cell has been taken into account in this model; results were compared with water medium. Besides, total absorbed doses have been calculated for the radionuclides distributed randomly within the cell and clusters. Cross-fire irradiation has been considered for clusters of cells. In this case, absorbed doses per cell within a cluster were found to be significantly higher than absorbed doses per single cell, depending on the cluster size. Results showed that ¹³¹I is a promising radionuclide for therapy of tumors from millimeter to centimeter dimensions.