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1.
BackgroundFor radioimmunotherapy purposes, a chemical complex with high absorption in cancer tumor is required. New chemicals are to be examined for their concentration in tumor and healthy organs. These are labeled with β-emitting radioisotopes to irradiate the tumor while deposited inside it. AimTo study the capability of recently developed chemical complex in targeting cancer tumor and investigate the distribution of 153Sm-TPTTC in rat organs as function of time. Materials and methodsThe chemical complex – [ Tris(1,10-phenanthroline)Samarium(III)] trithiocyanate was prepared and labeled with 153Sm radioisotope. The labeled complex was injected to a population of tumor bearing mice. In 2, 4, 24, 48, 96 h after injection the animals were sacrificed and the concentration of Samarium complex was measured in various organs such as blood, heart, intestine, colon, liver, spleen, kidney, sternum and bone. ResultsThe concentration of the radiopharmaceutical in various organs was measured at different times. The temporal behavior of biodistribution of 153Sm-TPTTC was modeled and drawn as function of time. ConclusionIt is shown that 153Sm-TPTTC is concentrated in tumor tissue and liver much more than in other organs. The variation of pharmaceutical concentration in all organs is described with summation of eight exponential terms and it approximates our experimental data with precision better than 2%. 相似文献
2.
AimThe main purpose of this work was to develop a pharmacokinetic model for the bone pain palliation agent Samarium-153 ethylenediamine tetramethylene phosphonate ([ 153Sm]-EDTMP) in normal rats to analyze the behavior of the complex. BackgroundThe use of compartmental analysis allows a mathematical separation of tissues and organs to determine the concentration of activity in each fraction of interest. Biodistribution studies are expensive and difficult to carry out in humans, but such data can be obtained easily in rodents. Materials and methodsWe have developed a physiologically based pharmacokinetic model for scaling up activity concentration in each organ versus time. The mathematical model uses physiological parameters including organ volumes, blood flow rates, and vascular permabilities; the compartments (organs) are connected anatomically. This allows the use of scale-up techniques to predict new complex distribution in humans in each organ. ResultsThe concentration of the radiopharmaceutical in various organs was measured at different times. The temporal behavior of biodistribution of 153Sm-EDTMP was modeled and drawn as a function of time. ConclusionsThe variation of pharmaceutical concentration in all organs is described with summation of 6–10 exponential terms and it approximates our experimental data with precision better than 2%. 相似文献
3.
PurposeTo evaluate the impact on the radiation protection policies of the radiocontaminants in Samarium-153 ethylenediamine tetramethylene phosphonate ( 153Sm-EDTMP). MethodsThe internal contamination of patients treated with 153Sm-EDMTP for palliation of painful disseminated multiple bone metastases due to long-lived impurities was assessed by direct measurements. These measurements were coupled with dose-rate measurements close to their bodies and spectroscopic analysis of the residual activity in post-treatment radiopharmaceutical vials. ResultsWhole-body counting carried out in six patients showed a 30–81-kBq europium −152 plus europium-154 contamination. The 0.85 mean 152Eu- to - 154Eu activity ratio obtained by direct counting was similar to that assessed by analysis of post-treatment residual activities in twelve radiopharmaceutical vials following radiopharmaceutical injection. ConclusionsThe long-lived radiocontaminants in the patient's bodies and the treatment wastes require modifications of the applicable radiation protection policies. 相似文献
4.
The purpose of this study was to evaluate the degree of cytological radiation damage to peripheral blood lymphocytes induced by 153Sm-EDTMP applied for palliation of metastatic bone pain. Blood samples from 16 patients (46-82 years old), 10 without previous radiotherapy and 6 with previous radiotherapy, were collected before and one hour after the administration of a mean activity of 41.7+/-5.8 MBq/kg of 153Sm-EDTMP. Then the lymphocytes were cultured for cytokinesis block micronucleus (MN) assay. The number of MNper binucleated cells (BC) in patients without previous radiotherapy before the treatment was of 0.030 (+/- 0.016) and after one hour 0.035 (+/- 0.013), although we could find inter individual differences. The basal MN/BC of the patients with no previous radiotherapy was similar to the controls. The increment in the percentage of BC with MN was similar in patients with and without previous radiotherapy. The observed mean of MN/BC is equivalent to a dose range of 0.05 to 0.10 Gy of 153Sm-EDTMP in vitro. The relatively low frequency of lymphocyte with micronuclei after the exposure to 153Sm-EDTMP supported the contention that radiation damage in lymphocytes of patients with painful bone metastases is minimal. 相似文献
5.
153Sm-EDTMP is a radiopharmaceutical used in nuclear medicine for relief of metastatic bone pain with promising results, but there are few studies about the effects of 153Sm-EDTMP in human cells. This study was conducted for the evaluation of the cytogenetic effects of 153Sm-EDTMP in blood lymphocytes from patients with bone metastases (without previous radio or chemotherapy), using the chromosome aberration technique. The degree of cytological damage found in in vivo blood cells of patients was compared with those found in in vitro in an adjusted dose-response curve. Blood samples were collected before and 1 hr after the administration of 153Sm-EDTMP(about 42.31 MBq/kg). The frequency of structural chromosome aberration per cell observed in 1 hr samples (0.054+/-0.035 CA/cell) was higher than basal ones (0.031+/-0.026 CA/cell), although this difference was not statistically significant (p= 0.101). For in vitro assay, blood samples were exposed to different concentrations of 153Sm-EDTMP, during 1 hr (0.37-1.11 MBq/ml). An increase in the frequency of chromosome aberration per cell as a function of the radioactive concentration was found. The data were adjusted by linear regression model (Y= 3.52+/-2.24 x 10(-2) + 11.15+/-3.46 x 10(-2) X). The frequency of aberration/cell found in vivo was 0.054 and for the same activity in vitro was 0.098, this difference being statistically significant (p = 0.02). This result may be related to blood clearance, osteoblastic activity and individual variability. For a more accurate analysis, the study of more donors is necessary. 相似文献
6.
The biodistribution of [ 75Se]BISTAES was studied in guinea pigs. A higher concentration of radioactivity was observed in articular cartilage than in other tissues or organs. A minimal amount of radioactivity was found in the blood, muscle and bone. The compound was excreted rapidly in urine. The target to background ratios were encouraging. [ 75Se]BISTAES has potential as an articular cartilage imaging agent and further studies in osteoarthritic animals are merited. 相似文献
7.
Studies of radiobiological effects in murine rodents exposed to internal radiation in the wild or in laboratory experiments require dosimetric support. The main problem of bone marrow (BM) dosimetry for bone-seeking β-emitters is dosimetric modeling, because the bone is a heterogeneous structure with complex microarchitecture. To date, there are several approaches to calculating the absorbed dose in BM, which mostly use rough geometric approximations. Recently, in the framework of studies of people exposed to 90Sr in the Urals, a new approach (SPSD) has been developed. The aim of the current study was to test for the first time the possibility of extension of the SPSD approach elaborated for humans to mice. For this, computational phantoms of femur bones of laboratory animals (C57BL/6, C57BL/6 J, BALB/c, BALB/cJ) aged 5–8 weeks (growing) and?>?8 weeks (adults) were created. The dose factors DFSr-90(BM?←?TBV?+?CBV) to convert the Sr isotope activity concentration in a bone tissue into units of dose rate absorbed in the bone marrow were 1.75?±?0.42 and 2.57?±?0.93 μGy day?1 per Bq g?1 for growing and adult animals, respectively, while corresponding values for DFSr-89(BM?←?TBV?+?CBV) were 1.08?±?0.27 and 1.66?±?0.67 μGy day?1 per Bq g?1, respectively. These results are about 2.5 times lower than skeleton-average DFs calculated assuming homogenous bone, where source and target coincide. The results of the present study demonstrate the possibility of application of the SPSD approach elaborated for humans to non-human mammals. It is concluded that the study demonstrates the feasibility and appropriateness of application of the SPSD approach elaborated for humans to non-human mammals. This approach opens up new prospects for studying the radiobiological consequences of red bone marrow exposure for both laboratory and wildlife mammals. 相似文献
8.
AimThe aim of this study was to estimate the secondary malignancy risk from the radiation in FFB prostate linac-based radiotherapy for different organs of the patient. BackgroundRadiation therapy is one of the main procedures of cancer treatment. However, the application the radiation may impose dose to organs of the patient which can be the cause of some malignancies. Materials and methodsMonte Carlo (MC) simulation was used to calculate radiation doses to patient organs in 18 MV linear accelerator (linac) based radiotherapy. A humanoid MC phantom was used to calculate the equivalent dose s for different organs and probability of secondary cancer, fatal and nonfatal risk, and other risks and parameters related to megavoltage radiation therapy. In out-of-field radiation calculation, it could be seen that neutrons imparted a higher dose to distant organs, and the dose to surrounding organs was mainly due to absorbed scattered photons and electron contamination. ResultsOur results showed that the bladder and skin with 54.89 × 10 −3 mSv/Gy and 46.09 × 10 −3 mSv/Gy, respectively, absorbed the highest equivalent dose s from photoneutrons, while a lower dose was absorbed by the lung at 3.42 × 10 −3 mSv/Gy. The large intestine and bladder absorbed 55.00 × 10 −3 mSv/Gy and 49.08 × 10 −3, respectively, which were the highest equivalent dose s due to photons. The brain absorbed the lowest out-of-field dose, at 1.87 × 10 −3 mSv/Gy. ConclusionsWe concluded that secondary neutron portion was higher than other radiation. Then, we recommended more attention to neutrons in the radiation protection in linac based high energy radiotherapy. 相似文献
9.
IntroductionOncolytic viruses show promise for treating cancer. However, to assess therapy and potential toxicity, a noninvasive imaging modality is needed. This study aims to determine the in vivo biodistribution, and imaging and timing characteristics of a vaccinia virus, GLV-1h153, encoding the human sodium iodide symporter (hNIS. MethodsGLV-1h153 was modified from GLV-1h68 to encode the hNIS gene. Timing of cellular uptake of radioiodide 131I in human pancreatic carcinoma cells PANC-1 was assessed using radiouptake assays. Viral biodistribution was determined in nude mice bearing PANC-1 xenografts, and infection in tumors confirmed histologically and optically via Green Fluorescent Protein (GFP) and bioluminescence. Timing characteristics of enhanced radiouptake in xenografts were assessed via 124I-positron emission tomography (PET). Detection of systemic administration of virus was investigated with both 124I-PET and 99m-technecium gamma-scintigraphy. ResultsGLV-1h153 successfully facilitated time-dependent intracellular uptake of 131I in PANC-1 cells with a maximum uptake at 24 hours postinfection (P<0.05). In vivo, biodistribution profiles revealed persistence of virus in tumors 5 weeks postinjection at 10 9 plaque-forming unit (PFU)/gm tissue, with the virus mainly cleared from all other major organs. Tumor infection by GLV-1h153 was confirmed via optical imaging and histology. GLV-1h153 facilitated imaging virus replication in tumors via PET even at 8 hours post radiotracer injection, with a mean %ID/gm of 3.82±0.46 (P<0.05) 2 days after intratumoral administration of virus, confirmed via tissue radiouptake assays. One week post systemic administration, GLV-1h153-infected tumors were detected via 124I-PET and 99m-technecium-scintigraphy. ConclusionGLV-1h153 is a promising oncolytic agent against pancreatic cancer with a promising biosafety profile. GLV-1h153 facilitated time-dependent hNIS-specific radiouptake in pancreatic cancer cells, facilitating detection by PET with both intratumoral and systemic administration. Therefore, GLV-1h153 is a promising candidate for the noninvasive imaging of virotherapy and warrants further study into longterm monitoring of virotherapy and potential radiocombination therapies with this treatment and imaging modality. 相似文献
10.
Background aimsTumor antigen-specific cytotoxic T lymphocytes (CTL) have been used in the treatment of human cancer, including leukemia. Several studies have established PR1 peptide, an HLA-A2.1-restricted peptide derived from proteinase 3 (P3), as a human leukemia-associated antigen. PR1-specific CTL elicited in vitro from healthy donors have been shown to lyse P3-expressing AML cells from patients. We investigated whether PR1-CTL can be adoptively transferred into NOD/SCID mice to eliminate human leukemia cells. MethodsPR1-CTL were generated in bulk culture from peripheral blood mononuclear cells (PBMC) stimulated with autologous dendritic cells. Human acute myeloid leukemia (AML) patient samples were injected and engrafted in murine bone marrow at 2 weeks post-transfer. ResultsFollowing adoptive transfer, bone marrow aspirate from mice that received AML alone had 72–88% blasts in a hypercellular marrow, whereas mice that received AML plus PR1-CTL co-infusion had normal hematopoietic elements and only 3–18% blasts in a hypocellular marrow. The PR1-CTL persisted in the bone marrow and liver and maintained a CD45RA ? CD28 + effector phenotype. ConclusionsWe found that adoptive transfer of PR1-CTL generated in vitro is associated with reduced AML cells in NOD/SCID mice. PR1-CTL can migrate to the sites of disease and maintain their capacity to kill the AML cells. The surface phenotype of PR1-CTL was consistent with their trafficking pattern in both vascular and end-organ tissues. 相似文献
11.
The objective of the present work is to apply the plasma clearance parameters to strontium, previously determined in our laboratory,
to improve the biokinetic and dosimetric models of strontium-90 ( 90Sr) used in radiological protection; and also to apply this data for the estimation of the radiation doses from strontium-89
( 89Sr) after administration to patients for the treatment of the painful bone metastases. Plasma clearance and urinary excretion
of stable strontium tracers of strontium-84 ( 84Sr) and strontium-86 ( 86Sr) were measured in GSF-National Research Center for Environment and Health (GSF) in 13 healthy German adult subjects after
intravenous injection and oral administration. The biological half-life of strontium in plasma was evaluated from 49 plasma
concentration data sets following intravenous injections. This value was used to determine the transfer rates from plasma
to other organs and tissues. At the same time, the long-term retention of strontium in soft tissue and whole body was constrained
to be consistent with measured values available. A physiological urinary path was integrated into the biokinetic model of
strontium. Parameters were estimated using our own measured urinary excretion values. Retention and excretion of strontium
were modeled using compartmental transfer rates published by the International Commission on Radiological Protection (ICRP),
the SENES Oak Ridge Inc. (SENES), and the Urals Research Center for Radiation Medicine (TBM). The results were compared with
values calculated by applying our GSF parameters (GSF). For the dose estimation of 89Sr, a bone metastases model (GSF-M) was developed by adding a compartment, representing the metastases, into the strontium
biokinetic model. The related parameters were evaluated based on measured data available in the literature. A set of biokinetic
parameters was optimized to represent not only the early plasma kinetics of strontium but also the long-term retention measured
in soft tissue and whole body. The ingestion dose coefficients of 90Sr were computed and compared with different biokinetic model parameters. The ingestion dose coefficients were calculated
as 2.8 × 10 −8, 2.1 × 10 −8, 2.5 × 10 −8 and 3.8 × 10 −8 Sv Bq −1 for ICRP, SENES, TBM and GSF model parameters, respectively. Moreover, organ absorbed dose for the radiopharmaceutical of
89Sr in bone metastases therapy was estimated based on the GSF and ICRP biokinetic model parameters. The effective doses were
3.3, 1.8 and 1.2 mSv MBq −1 by GSF, GSF-M, and ICRP Publication 67 model parameters, respectively, compared to the value of 3.1 mSv MBq −1 reported by ICRP Publication 80. The absorbed doses of red bone marrow and bone surface, 17 and 21 mGy MBq −1 calculated by GSF parameters, and 7.1 and 8.8 mGy MBq −1 by GSF-M parameters, are comparable to the clinical results of 3–19 mGy MBq −1 for bone marrow and 16 mGy MBq −1 for bone surface. Based on the GSF-M model, the absorbed dose of 89Sr to metastases was estimated to be 434 mGy MBq −1. The strontium clearance half-life of 0.25 h from the plasma obtained in the present study is obviously faster than the value
of 1.1 h recommended by ICRP. There are no significant changes for ingestion dose coefficients of 90Sr using different model parameters. A model including the metastases was particularly developed for dose estimation of 89Sr treatment for the pain of bone metastases. 相似文献
12.
The Mayak Production Association released large amounts of 90Sr into the Techa River (Southern Urals, Russia) with peak amounts in 1950–1951. Techa Riverside residents ingested an average
of about 3,000 kBq of 90Sr. The 90Sr-body burden of approximately 15,000 individuals has been measured in the Urals Research Center for Radiation Medicine in
1974–1997 with use of a special whole-body counter (WBC). Strontium-90 had mainly deposited in the cortical part of the skeleton
by 25 years following intake, and 90Sr elimination occurs as a result of cortical bone resorption. The effect of 90Sr-radiation exposure on the rate of cortical bone resorption was studied. Data on 2,022 WBC measurements were selected for
207 adult persons, who were measured three or more times before they were 50–55 years old. The individual-resorption rates
were calculated with the rate of strontium recirculation evaluated as 0.0018 year −1. Individual absorbed doses in red bone marrow (RBM) and bone surface (BS) were also calculated. Statistically significant
negative relationships of cortical bone resorption rate were discovered related to 90Sr-body burden and dose absorbed in the RBM or the BS. The response appears to have a threshold of about 1.5-Gy RBM dose.
The radiation-induced decrease in bone resorption rate may not be significant in terms of health. However, a decrease in bone
remodeling rate can be among several causes of an increased level of degenerative dystrophic bone pathology in exposed persons. 相似文献
13.
PurposeX-ray dose reduction using additional copper filters (Cu-filters) for abdominal general radiography was indicated in a report using a simulation study. We validated the dose reduction effects using a clinical digital radiography system equipped with an indirect-type CsI detector and an automatic Cu-filter insertion function. MethodsThe image qualities were evaluated using signal difference-to-noise ratio (SDNR) for different radiation qualities with and without Cu-filters for a 20-cm acrylic phantom. Acrylic and bone equivalent material plates were used for contrast measurements. The dose reduction using Cu-filters was estimated from the ratios of the SDNR 2 values. ResultsFor the same entrance surface dose (ESD), Cu-filters with 0.1- and 0.2-mm thicknesses increased the image quality as evaluated by SDNR 2 and the estimated dose reduction without degrading the image quality. For the acrylic contrast, the dose reductions with the 0.1- and 0.2-mm-thick Cu-filters were approximately 30% and 44% at 70 kV and 29% and 35% at 80 kV, respectively. For the bone contrast, the reduction rates were slightly reduced. ConclusionsWe validated the dose reduction capability of additional Cu-filters without degrading the image quality for abdominal radiography. The estimated entrance surface dose reductions of the Cu-filters were approximately 30–40% and 20–30% for the acrylic and bone contrasts, respectively, and effective dose reductions for acrylic were nearly half of those for ESD. At these reduced dose conditions, the current time product values needed to be increased by factors of 1.4 and 1.8 for the 0.1- and 0.2-mm-thick Cu-filters, respectively. 相似文献
14.
Implantable miniature thermoluminescent dosimeters and conventional biodistribution analysis were used to determine the locally absorbed radiation dose delivered to three morphologically distinct human renal cell carcinoma xenografts (TK-39, TK-82 and TK-177C; N = 87) following a 50 μCi infusion of 131iodine-labeled monoclonal antibody A6H. Xenografts were clearly detected by radioimmunoscintigraphy. Pronounced differences were noted among the three xenografts in MAb pharmacokinetics and in the locally absorbed irradiation doses which ranged from 2 to 5cGy per injected μCi of 131iodine-labelled A6H. 相似文献
15.
Samarium-153 is a radionuclide which can be produced in high yield by neutron irradiation and which has nuclear properties that make it attractive for use as a radiotherapeutic agent. Several phosphonate complexes of 153Sm were synthesized and characterized by electrophoresis and HPLC. A procedure based on cation exchange chromatography was developed for measuring complex yields. The complexes could be produced in yields greater than 99%, were anionic, and most exhibited a single HPLC peak. 相似文献
16.
PurposeThe objective of this study was to evaluate the toxicity, the absorbed dose to critical organs and tumour of B-B4 monoclonal antibody labeled with Iodine 131 in patients with multiple myeloma (MM) enrolled in a phase I study. Patients and methodFour patients with MM were enrolled and received for dosimetric study an injection of 20 mg/m 2 of B-B4 coupled with 370 MBq of Iodine 131. During the treatment phase, after viewing the target, three patients received a fixed dose of 20 mg/m 2 of 131I-B-B4 with an initial activity of 555 MBq/m 2, corresponding to level 1. ResultsImmunoscintigraphy showed an early and intensive uptake of the axial skeleton confirming the targeting of the disease by the antibody. Grade 3/4 haematological toxicity was observed in two patients with a trend to tally with the estimated average dose received by the bone marrow, calculated in the dosimetric study (blood method and imaging method). No other toxicity was observed. No complete or partial response was observed. ConclusionThe dose of 555 MBq/m 2 of 131I-B-B4 has shown encouraging results in terms of dosimetry and toxicity of RIT in MM. Other developments are possible with the use of humanized monoclonal antibody and the labeling with an alpha particle emitter. 相似文献
17.
The research objective is assessment of structural genomic damages in plutonium workers. The study group included workers
of the Mayak Production Association subject to chronic occupational internal exposure to incorporated 239Pu and/or external γ-rays. A lymphocyte culture of peripheral blood was chosen as an object of study. The yield of intrachromosomal
exchange aberrations of chromosomal type on stained slides was analyzed using fluorescent in situ hybridization, mBAND. Linear
relationships were revealed between (a) the total yield of chromosome-type aberrations (intra- and inter-chromosomal ones)
and the absorbed dose from external exposure of the red bone marrow (RBM) to γ rays, the absorbed dose from internal exposure
of the RBM to α-radiation from incorporated 239Pu, and 239Pu body burden, and (b) the yield of intrachromosomal aberrations and an absorbed dose from internal exposure of the RBM to
239Pu and 239Pu body burden. 相似文献
18.
It is well known that rare earth elements (REEs) have come into extensive use in a number of fields. As a result, REEs are
becoming closely related to human's daily life. However, until now, the distributions of REEs in the brain are not yet very
clear. In this study, Sprague-Dawley male rats were intraperitoneally injected with 0.25 mL of 153SmCl 3 solution (containing 10 μg Sm). The brain were perfused with saline to minimize the blood influence. The radioactivities
of 153Sm in the five brain regions (hypothalamus, cerebellum, hippocampus, corpus striatum, and cerebral cortex) were counted. The
results suggested that Sm did enter into the brain. Although only about 0.0003% of the given dose was accumulated in the brain,
Sm seemed to be remain in the brain for a long time. The highest amounts and lowest concentrations of 153Sm were found in the cerebral cortex, and the highest concentrations of 153Sm were found in the hypothalamus. 相似文献
19.
BackgroundThe aim of the study was to assess the dosimetric comparison of bone marrow between standard IMRT(SD-IMRT) and bone marrow sparing IMRT (BMS-IMRT) among carcinoma cervix patients who underwent radical or adjuvant chemoradiation in a tertiary cancer center. Materials and methodsForty eligible patients of histo-pathologically proven carcinoma cervix were enrolled in the study that was randomized on a 1:1 basis between SD-IMRT and BMS-IMRT from July 2018 to October 2019. The whole pelvis, bilateral femoral heads, and upper 1/3 rd femur were contoured using the whole bone technique as a surrogate marker for the bone marrow. In both arms, V10, V20, and V40, bone marrow was noted along with mean, maximum, minimum dose, and total volume. DVH for the bone marrow in both arms was compared using the unpaired student t-test. ResultsWe found no significant difference in the mean of various parameters in SD-IMRT arm vs. BMS IMRT arm — for the bone marrow: V10 (89 ± 4.3% vs. 86.7 ± 3.7%), V20 (73.2 ± 5.3% vs. 73.1 ± 4.5%), V40 (23.9 ± 5.4% vs. 26.6 ± 7.4%) and, similarly, for mean dose (28.1 ± 3.5% vs. 28.1 ± 1.8%), maximum dose (53.4 ± 0.58% vs. 53.2 ± 0.58%), minimum dose (0.33 ± 0.18% vs. 0.38 ± 0.38%), total volume (961 ± 110 cc vs. 901 ± 152 cc). ConclusionThis study shows no statistically significant difference in dosimetry between the two groups, which suggests that SD-IMRT spares the bone marrow adequately. Therefore, the need for BMS-IMRT using the present contouring technique does not give any added advantage over SD-IMRT. However, large sample size, other novel contouring technique, and multivariate analysis are needed to reach a definite conclusion. 相似文献
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