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Biomedical subjects

M G Stabin

Publications and source records attributed to M G Stabin.

At least 19 recordsLinked to original sources

Biodistribution and dosimetry of iodine-123-labelled Z-MIVE: an oestrogen receptor radioligand for breast cancer imaging.

This study reports on the distribution and radiation dosimetry of iodine-123-labelled cis-11beta-methoxy-17alpha-iodovinyloestradiol (Z-[123I]MIVE), a promising radioligand for imaging of oestrogen receptors (ERs) in human breast cancer. Whole-body scans were performed up to 24 h after intravenous injection of 138-193 MBq Z-[123I]MIVE in five healthy female volunteers, four with and one without thyroid blockade. Blood samples were taken at various times up to 24 h after injection. Urine was collected up to 24 h after injection in order to calculate renal clearance and to aid in the interpretation of whole-body clearance, including faecal excretion. Time-activity curves were generated for the thyroid, heart, brain, breasts and liver, by fitting the organ-specific geometric mean counts, obtained from regions of interest, to a multicompartmental model. The MIRD formulation, using 11 source organs, was applied to calculate the absorbed radiation doses for various organs upon administration of Z-[123I]MIVE. The images showed rapid hepatobiliary excretion which resulted in good imaging conditions for the thoracic region. Imaging of the abdominal region was impeded due to extensive bowel activity. Diffuse uptake and retention of activity was seen in breast tissue, the breast-to-non-specific uptake ratio increasing over time. Z-[123I]MIVE was cleared by both the kidneys and the gastrointestinal tract. At 50 h p.i. the mean excretion in urine was predicted to be 58%+/-14% (SD) and that in faeces 31%+/-19%. If the thyroid was not blocked, it was the most critical organ (0.33 mGy/MBq). In general, the excretory organs received the highest absorbed doses, i.e. the lower and upper large intestinal walls (0.11 and 0.098 mGy/MBq, respectively), the urinary bladder wall (0.090 mGy/MBq), the gallbladder wall (0.087 mGy/MBq) and the small intestine (0.043 mGy/MBq). The average effective dose equivalent of Z-[123I]MIVE was estimated to be 0.033 mSv/MBq. The amount of Z-[123I]MIVE required for adequate breast cancer ER imaging results in an acceptable effective dose equivalent to the patient.

Adult

Monte Carlo simulation of diffusion and reaction in water radiolysis--a study of reactant 'jump through' and jump distances.

In Monte Carlo simulations of water radiolysis, the diffusion of reactants can be approximated by "jumping" all species randomly, to represent the passage of a short period of time, and then checking their separations. If, at the end of a jump, two reactant species are within a distance equal to the reaction radius for the pair, they are allowed to react in the model. In principle, the possibility exists that two reactants could "jump through" one another and end up with a separation larger than the reaction radius with no reaction being scored. Ignoring this possibility would thus reduce the rate of reaction below that intended by such a model. By making the jump times and jump distances shorter, any error introduced by 'jump through' is made smaller. This paper reports numerical results of a systematic study of 'jump through' in Monte Carlo simulations of water radiolysis. With a nominal jump time of 3 ps, it is found that more than 40% of the reactions of the hydrated electron with itself and of the H atom with itself occur when reactions during 'jump through' are allowed. For all other reactions, for which the effect is smaller, the contributions of 'jump through' lie in the range 1%-16% of the total. Corrections to computed rate constants for two reactions are evaluated for jump times between 0.1 and 30 ps. It is concluded that jump-through corrections are desirable in such models for jump times that exceed about 1 ps or even less. In a separate study, we find that giving all species of a given type the same size jump in a random direction yields results that are indistinguishable from those when the jump sizes are selected from a Gaussian distribution. In this comparison, the constant jump size is taken to be the root-mean-square jump size from the Gaussian distribution.

Models, Chemical

Human biodistribution and dosimetry of [123I]FP-CIT: a potent radioligand for imaging of dopamine transporters.

This study reports on the biodistribution and radiation dosimetry of iodine-123-labelled N-omega-(flu- oropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I]FP-CIT), a promising radioligand for the imaging of dopamine transporters. In 12 healthy volunteers, conjugate whole-body scans were performed up to 48 h following intravenous injection of approximately 100 MBq [123I]FP-CIT. Attenuation correction was performed using a transmission whole-body scan obtained prior to injection of the radioligand, employing a 123I flood source. Blood samples were taken and urine was freely collected up to 48 h after injection of the radiotracer. For each subject, the percentage of injected activity measured in regions of interest over brain, striatum, lungs and liver were fitted to a multicompartmental model to give time-activity curves. The cumulative urine activity curve was used to model the urinary excretion rate and, indirectly, to predict faecal excretion. Using the MIRD method, nine source organs were considered in estimating absorbed radiation doses for organs of the body. The images showed rapid lung uptake and hepatobiliary excretion. Diffuse uptake and retention of activity was seen in the brain, especially in the striatum. At 48 h following the injection of [123I]FP-CIT, mean measured urine excretion was 60%+/-9% (SD), and mean predicted excretion in faeces was 14%+/-1%. In general, the striatum received the highest absorbed dose (average 0.23 mGy/MBq), followed by the urinary bladder wall (average 0.054 mGy/MBq) and lungs (average 0.043 mGy/MBq). The average effective dose equivalent of [123I]FP-CIT was estimated to be 0.024 mSv/MBq. The amount of [123I]FP-CIT required for adequate dopamine transporter imaging results in an acceptable effective dose equivalent to the patient.

Adult

Technetium-99m-labeled anti-EGF-receptor antibody in patients with tumor of epithelial origin: I. Biodistribution and dosimetry for radioimmunotherapy.

UNLABELLED: Accurate estimation of biodistribution and absorbed dose to normal organs and tumors is important for immunoscintigraphic studies and radioimmunotherapy treatment planning. METHODS: Four patients (3 men, 1 woman; mean age 54.8 +/- 9.2 yr; range 42-64 yr) were administered 3 mg of anti-human epidermal growth factor receptor (anti-hEGF-r) antibody (ior egf/r3), radiolabeled with 99mTc activity of 39.5 +/- 1.1 mCi (range 38.5 mCi-40.7 mCi) by intravenous bolus infusion. After administration, blood and urine samples were collected from three patients up to 24 hr after injection. Whole-body anterior and posterior scans were obtained at 5 min and 1, 3, 5 and 24 hr after injection. Using a computer program, regions of interest were drawn over the heart, liver, spleen, bladder and tumor to measure the activity in the source organs at each scanning time. Time-activity curves for each source organ were then fitted to monoexponential or biexponential functions by nonlinear least squares regression using the flexible polyhedrals method, which adequately fit our data with the correlation coefficient of 0.985 +/- 0.013, and were integrated to determine organ residence times. The mean absorbed doses to the whole body and various normal organs were then estimated from residence times and from blood and urine samples using the methods developed by the Medical Internal Radiation Dose Committee. The effective dose equivalent and effective dose were calculated as prescribed in ICRP Publication Nos. 30 and 60. RESULTS: Plasma disappearance curves of 99mTc-labeled anti-hEGF-r antibody were best-fit by a two-compartment model in all patients with a distribution half-life (t(1/2alpha)) of 0.207 hr +/- 0.059 hr (mean +/- s.d., n = 3) and an elimination half-life (t(1/2beta)) of 13.9 hr +/- 2.2 hr. Among the various organs, significant accumulation of the radiolabeled antibody was found in the liver (48.5% +/- 4.4%, mean +/- s.d.), heart (3.50% +/- 0.17%) and spleen (3.1% +/- 1.8%) at 5 min postadministration. These values were reduced to 3.2% +/- 0.4%, 0.1% +/- 0.01% and 0.1% +/- 0.1%, respectively, at 24 hr. Mean cumulative urinary excretion of 99mTc-labeled anti-hEGF-r antibody was 4.6% +/- 0.6% at 24 hr postinjection. Estimates of radiation absorbed dose to normal organs in rad/mCi administered (mean +/- s.d., n = 4) were: whole body 0.017 +/- 0.002; gallbladder wall 0.074 +/- 0.007; spleen 0.136 +/- 0.076; and liver 0.267 +/- 0.036. The effective dose equivalent and effective dose estimates for adults were 0.041 +/- 0.008 rem/mCi and 0.027 +/- 0.004 rem/mCi administered. CONCLUSION: This feasibility study indicates that 99mTc-labeled anti-hEGF-r antibody (ior egf/r3) can be used safely; this analysis provides a dosimetric framework for future studies. This monoclonal antibody, labeled with 188Re, could possibly permit a successful regional radioimmunotherapy of tumors of epithelial origin.

Adult

Dosimetry of pediatric nuclear medicine procedures.

BACKGROUND: Radiation dose estimates for children of different ages for many different nuclear medicine procedures are presented. METHODS: Using standard MIRD methodology, radiation dose calculations were performed for a broad range of radiopharmaceutical agents commonly used in pediatric nuclear medicine. Results from the best available biokinetic models were used in the MIRDOSE 3.1 computer program to obtain dose estimates per unit administered activity for the procedures. Then, assuming typical values of administered activity based on body weight, the dose per procedure for many target organs of interest was calculated and presented in tabular form. The effective dose equivalent (ICRP 30) and effective dose (ICRP 60) are also given. RESULTS AND CONCLUSIONS: The results are presented in multiple tables attached to the text of the article. The information should be quite useful in evaluating radiation doses for many pediatric nuclear medicine procedures, using the best available models and methods.

Adolescent

Rhenium-188 hydroxyethylidene diphosphonate: a new generator-produced radiotherapeutic drug of potential value for the treatment of bone metastases.

The search for an ideal radioisotope for systemic radiotherapy continues. As a generator-produced radioisotope emitting both beta and gamma rays and having a short physical half-life of 16.9 h, rhenium-188 is a very good potential candidate for systemic radiotherapy. In this study, we labeled hydroxyethylidene diphosphonate (HEDP) with 188Re and analyzed the biodistribution and bone uptake following intravenous injection in rats to assess its potential for clinical use. The rats were injected with approximately 14.8 MBq (0.4 mCi) 188Re-HEDP in a volume of 0.1 ml intravenously and then sacrificed at 1 h, 24 h, or 48 h (four rats at each time). Samples (about 0.1 g) of lung, liver, kidney, spleen, testis, muscle, stool, and bone (thoracic vertebra) were taken and weighed carefully. In addition, a 1-ml sample of blood was drawn from the heart and 1 ml of urine was taken from the urinary bladder immediately after killing. Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter (% ID/g or ml). Bone lesions were created in the right tibial bone in three rabbits to calculate the lesion to normal uptake ratio (L/N ratio). The biodistribution data showed that the radioactivity in the bone tissue was as high as 1.877% ID/g at 1 h and that it climbed to 2.017% ID/g at 4 h. The activity level in the kidney was highest at 1 h but declined rapidly throughout the study. The radioactivities in the lung, liver, muscle, spleen, testis, blood, and stool were all lower than 0.3% ID/g at 1 h and also declined rapidly. The biological half-life in bone was the longest (60.86 h). In contrast, the biological half-lives in muscle and blood were short (2.99 h and 6.21 h respectively). The concentrations of radioactivity in muscle, spleen, testis, and stool were quite low throughout the study. Most of the radiotracer was excreted by the urinary system. The L/N ratio was 4.23+/-0.21 in rabbits injected with 188Re-HEDP and 4.25+/-0.23 in those injected with technetium-99m methylene diphosphonate. In conclusion, we would suggest that 188Re-HEDP is a very good potential candidate for the treatment of bone metastases because of the following characteristics: (1) it is generator produced; (2) it has a short half-life; (3) it emits gamma rays suitable for imaging; (4) there is highly selective uptake in the skeletal system and bone lesions; and (5) it has a low non-target uptake and rapid clearance in nonosseous tissue.

Animals

Tissue distribution and radiation dosimetry of astatine-211-labeled chimeric 81C6, an alpha-particle-emitting immunoconjugate.

A paired-label study was performed in athymic mice bearing subcutaneous D-54 MG human glioma xenografts to compare the localization of human/mouse anti-tenascin chimeric antibody 81C6 labeled by reaction with N-succinimidyl 3-[211At]astatobenzoate and N-succinimidyl 3-[131I]iodobenzoate. Over the 48-h observation period, the distribution of 211At- and 131I-labeled antibody were quite similar in tumor and normal tissues except stomach. These data were used to calculate human radiation doses for both intravenously and intrathecal administered 211At-labeled chimeric 81C6 using a quality factor of 5 for alpha-emissions.

Animals

Review of the fetal radiation doses received from 59Fe kinetic studies at Vanderbilt University in the 1940's.

Fetal radiation dose estimates were calculated for women who received oral administrations of 59Fe at Vanderbilt University in the 1940's. A similar dosimetry analysis was performed by Dyer and Brill in 1972; the availability of recently developed physical models of the pregnant female at different stages of gestation and of a new kinetic model for iron metabolism afforded an opportunity to re-evaluate these doses. Radiation dose estimates for the fetus (and fetal liver in three cases) were calculated for a number of oral and intravenous studies using these new models and the available data about the original experiments. The total fetal doses do not appear to have exceeded a few hundred microgray (a few tens of millirad) for the majority of the study subjects. Considerable uncertainty exists, however, in the amount of activity administered to these subjects.

Administration, Oral

Placental transfer of radiopharmaceuticals and dosimetry in pregnancy.

The calculation of radiation dose estimates to the fetus is often important in nuclear medicine. To obtain the best estimates of radiation dose to the fetus, the best biological and physical models should be employed. In this paper the most recent data available on the placental crossover of many radiopharmaceuticals are presented. This information was used with standard kinetic models describing the maternal distribution and retention and with the best available physical models to obtain fetal dose estimates for these radiopharmaceuticals at all stages of pregnancy (presented in a separate paper). The literature yielded information on placental crossover of 15 radiopharmaceuticals, from animal or human data. From these data, radiation dose estimates were developed in early pregnancy and at 3, 6, and 9 mo gestation for these radiopharmaceuticals, as well as for many others used in nuclear medicine (the latter considering only maternal organ contributions to fetal dose).

Adult

Radiation absorbed dose to the embryo/fetus from radiopharmaceuticals.

Radiation protection practice requires the knowledge of estimated absorbed radiation doses to aid in the understanding of the potential detriment of various exposures. In nuclear medicine, the radiation doses to the internal organs of the subject are commonly calculated using the MIRD methods and equations. The absorbed dose to the embryo or fetus has long been an area of concern. The recent release of the pregnant female phantom series, and its incorporation into the MIRDOSE 3 computer software, has made possible the estimation of absorbed doses from radionuclides in the body to the fetus in early pregnancy and at 3, 6, and 9 mo gestation. A survey of several major medical institutions was made to determine the radiopharmaceuticals which might be given, whether intentionally or not, to women of childbearing years. Biokinetic data for these radiopharmaceuticals were gathered from various documents and other resources, and the absorbed doses to the embryo and fetus at these different stages of gestation from radiations originating within the mother's organs were estimated. In addition, information about activity distributed within the placenta and fetus was included where quantitative data were available. These absorbed dose estimates can be used to evaluate the risk associated with the use of different radiopharmaceuticals so that a more informed evaluation of the risks and benefits of the different procedures may be made. Further research is needed into the mechanisms and quantitative aspects of the placental transfer of many radiopharmaceuticals.

Embryo, Mammalian

Health concerns related to radiation exposure of the female nuclear medicine patient.

The female nuclear medicine patient is of special concern in evaluating radiation dose and risk in nuclear medicine. The female's overall body size and organ sizes generally are smaller than those of her male counterpart (thus her radiation doses will be higher, given the same amounts of administered activity and similar biokinetics); female gonads are inside the body instead of outside and are near several organs often important as source organs in internal dosimetry (urinary bladder, liver, kidneys, intestines); risk of breast cancer is significantly higher among females than males; and in the case of pregnancy, exposure to radiation of the embryo/fetus and the nursing infant are of special concern in such an analysis. All these concerns are addressed in this study through a comparative study of radiation doses for males and females over a large number (approximately 60) of nuclear medicine studies and through a study of what is known about radiation dosimetry in pregnancy and breast feeding. It was found that women's critical organ doses and effective doses (as defined by the International Commission on Radiological Protection 60 [ICRP 60] are about 25% higher than those for men across all these studies. Women's gonad doses, however, may be as much as 10 to 30 times higher than those in men, although 2- to 3-fold differences are common. Many radiopharmaceuticals are administered to women of childbearing age; however, little is known about how much activity crosses the placenta and about the biokinetics in the fetus should it occur. Nonetheless, dose estimates are provided at four stages of pregnancy (early, 3-month, 6-month, and 9-month gestation) for a large number of radiopharmaceuticals, whether or not quantitative estimates of placental crossover can be made. Many radiopharmaceuticals are also excreted in breast milk of nursing mothers. Breast feeding interruption schedules are suggested through analysis of the observed kinetics of these pharmaceuticals and an assumed dose limit of 1 mSv (effective dose equivalent) to the infant.

Female

Radiation dosimetry for indium-111-pentetreotide.

UNLABELLED: We present radiation dose estimates for 111In-pentetreotide. METHODS: Kinetic data were gathered in 10 subjects at two different sites. A compartmental model was used to fit the data, including retention, in three major organs and excretion. RESULTS: The data were consistent for the subjects at both sites. The organ receiving the highest dose was the kidneys (0.52 mGy/MBq); the effective dose equivalent was 0.1 mSv/MBq, and the effective dose was 0.073 mSv/MBq. CONCLUSION: The results of this study provide the basis for evaluation of radiation safety of this drug.

Adult

Radiation dose from breastfeeding following administration of thallium-201.

UNLABELLED: Radiation exposure to a breast feeding infant was estimated when the mother underwent a nuclear medicine procedure using 201Tl. METHODS: A lactating mother was administered 111 MBq of 201Tl for a brain scan. Breast milk samples were collected over a period of three days, and the rate of 201Tl secretion was determined. The infant was not breast fed during that time. Based on our data, we determined the time-activity function for radioactivity in the breast milk. From these data, and assuming an intake of 1000 ml/day, we calculated the fraction of administered activity that might be taken in by the infant. We also calculated the intake assuming breastfeeding delays of 2, 24, 48, 72, 96 and 500 hr. RESULTS: We calculated the radiation dose to various organs and the effective dose to an infant and a 1-yr-old for breastfeeding delays of 2 to 500 hr. The effective dose to a 1-yr-old from an administration of 111 MBq of 201Tl to the mother ranged from 0.90 mSv to 0.00072 mSv, and the effective dose to a newborn ranged from 1.6 mSv to 0.0013 mSv depending on delay time. CONCLUSION: Our estimates of radiation exposure to an infant from breastfeeding indicate that in this case, a 1-yr-old would have received less than the NCRP's proposed limit on annual effective dose to members of the general public of 1 mSv with a 48-hr delay and no restrictions on holding the child. A newborn would have received less than the proposed infrequent exposure limit of 5 mSv without any delay or restrictions in breastfeeding.

Adult

Specific absorbed fractions of energy from internal photon sources in brain tumor and cerebrospinal fluid.

Transferrin, when injected intracranially into glioblastoma multiforme lesions, acts as a cytotoxic substance. Transferrin, radiolabeled with In-111, can be coinjected and subsequent scintigraphic imaging can demonstrate the biokinetics of the cytotoxic transferrin. The administration of 111In transferrin into a brain tumor results in distribution of radioactivity in the brain, brain tumor, and the cerebrospinal fluid (CSF). Information about absorbed radiation doses to these regions, as well as other nearby tissues and organs, is important for evaluating radiation-related risks from this procedure. The radiation dose is usually estimated for a mathematical representation of the human body. We have included source/target regions for the eye, lens of the eye, spinal column, spinal CSF, cranial CSF, and a 100-g tumor within the brain of an adult male phantom developed by Cristy and Eckerman. The mathematical models of the spinal column, spinal CSF, and the eyes were developed previously, however, these source/targets have not been routinely included in photon transport simulations. Specific absorbed fractions (SAFs) as a function of photon energy were calculated using the ALGAMP computer code, which utilizes Monte Carlo techniques for simulating photon transport. The ALGAMP code was run three times, with the source activity distributed uniformly within the tumor, cranial CSF, and the spinal CSF volumes. These SAFs, which were generated for 12 discrete photon energies ranging from 0.01 to 4.0 MeV, were used with decay scheme data to calculate S-values needed for estimating absorbed doses. S-values for 111In are given for three source regions (brain tumor, cranial CSF, and spinal CSF) and all standard target regions/organs, the eye and lens, as well as to tissues within these source regions. S-values for the skeletal regions containing active marrow are estimated. These results are useful in evaluating the radiation doses from intracranial administration of 111In transferrin. The SAFs are also generally useful for calculation of absorbed dose from any radionuclide in these source regions.

Adult

Bremsstrahlung radiation dose in yttrium-90 therapy applications.

UNLABELLED: The bremsstrahlung component of the decay scheme of beta emitters has been traditionally ignored in internal dosimetry calculations. METHODS: We have estimated the radiation dose from the bremsstrahlung component of the decay scheme of 90Y as a function of distance from a point source in a liquid medium and to body organs from distributed sources of 90Y in the liver and spleen. RESULTS: These estimates agree with measurements of bremsstrahlung dose measured in a Rando phantom, and give an estimate of the importance of this contribution to the overall dosimetry. CONCLUSIONS: The bremsstrahlung radiation absorbed dose contribution from an organ to itself is very small compared to that from the beta dose, but the contribution to other organs is not always negligible, especially when large amounts of 90Y may be involved, as in therapy applications.

Beta Particles

A model of the prostate gland for use in internal dosimetry.

UNLABELLED: Several radionuclides or radiolabeled pharmaceuticals may be taken up by the prostate gland. METHODS: A model of the prostate gland has been developed and implemented in the adult male mathematical phantom within software which calculates absorbed fractions of energy from activity in source regions within the phantom. RESULTS: Specific absorbed fractions are reported for all target regions within the phantom for 12 discrete source energies from 0.01 to 4.0 MeV. S-values for all target regions for six radionuclides are also reported. CONCLUSIONS: This work provides another organ useful for internal dose calculations within the 70-kg phantom.

Algorithms

Absorbed fractions for electrons and beta particles in spheres of various sizes.

UNLABELLED: The use of electron-emitting radionuclides in tumor imaging and therapy has presented some new challenges to conventional radiation dosimetry. The fraction of electron energy absorbed in most source regions has usually been assumed to be unity. In small structures such as localized tumors or isolated regions containing moderate to high energy electron emitters, however, this may not always be the case. METHODS: Using an extension of Berger's scaled absorbed dose distributions for point sources to represent a spherical geometry, absorbed fractions of electron energy for sources uniformly distributed in spheres of various sizes have been calculated. RESULTS: Beta particle and monoenergetic electron energies studied range from 0.025 to 4.0 MeV and sphere masses range from 0.01 to 1000 g. S values have also been calculated for 90Y, 123I and 131I based on the results of the absorbed fraction calculations. CONCLUSION: These calculated absorbed fractions are valuable in estimating electron energy loss from small spherical structures and may be useful in estimating the radiation dose to these small volumes.

Beta Particles