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1.
Purpose: Both β and γ sources of fixed length are currently used in the catheter-based intravascular brachytherapy (IVBT). Source stepping is often used to treat a lesion longer than the effective treatment length of the source. A major challenge for the stepping procedure is to attain a perfect dosimetric match (uniform dose) at the source junction. This work presents a quantitative and systematic dosimetric analysis for source stepping during an IVBT procedure. Materials and Methods: The three most commonly used β and γ sources (192Ir by BEST, 90Sr by NOVOSTE and 32P by Guidant) were studied using the EGSnrc Monte Carlo code. Dose distributions were calculated for a perfect end-to-end match and for a range of end-to-end gaps and overlaps between consecutive steps. Results: It is found that a perfect end-to-end match during source stepping yields uniform dose distribution in the region of source junction. The doses in the case of a mismatch (in the presence of an end-to-end gap or overlap) were found to be significantly different from those with the perfect end-to-end match. The dose deviation depends on the size of the gap or overlap, radial distance and type of source. The dose deviation decreases with radial distance for a given gap/overlap. For example, for a gap/overlap of 2 mm, dose decreases/increases of 30%, 55% and 60% were found at the radial distance of 2 mm from source for 192Ir, 90Sr and 32P, respectively. These dose deviations are reduced by approximately 10% when the radial distance increases from 2 to 3 mm. The dose deviations for gaps or overlaps in the range of 0–5 mm are presented. Conclusions: During an IVBT procedure involving source stepping, a perfect end-to-end match is always desired. Significant underdosing or overdosing can occur in the case of a source mismatch. A considerable caution should be exercised to ensure that sources are properly matched.  相似文献   

2.
NAD(P)H: quinone oxidoreductase 1 (NQO1) is an obligate two-electron reductase and is highly expressed in many human solid cancers. Because NQO1 can be induced immediately after exposure to ionizing radiation, we aimed to develop an NQO1-targeted radiolabeled agent to establish a novel internal radiation therapy that amplifies the therapeutic effects when combined with external radiation therapy. We designed three NQO1-targeted radioiodinated compounds including two ether linkage compounds ([125I]1 and [125I]2) and a sulfide linkage compound ([125I]3) based on the selective binding of indolequinone analogs to the active site of NQO1 by the stacking effect. These compounds were successfully prepared using an oxidative iododestannylation reaction with high radiochemical yields and purity. In NQO1-expressing tumor cells, [125I]1 and [125I]2 were readily metabolized to p-[125I]iodophenol or m-[125I]iodophenol and [125I]I, whereas over 85% of the initial radioactivity of [125I]3 was observed as an intact form at 1 h after incubation. The cellular uptake of [125I]3 was significantly higher than those of [125I]1 and [125I]2. The uptake of [125I]3 was specific and was dependent on the expression of NQO1. These data suggest that the novel NQO1-targeted radioiodinated compound [125I]3 could be used as a novel internal radiation agent for the treatment of cancer.  相似文献   

3.

Aim

The aim of this work was to assess the suitability of the use of a Gafchromic EBT2 film for the measurement of anisotropy function for microSelectron HDR 192Ir (classic) source with a comparative dosimetry method using a Gafchromic EBT2 film and thermoluminescence dosimeters (TLDs).

Background

Sealed linear radiation sources are commonly used for high dose rate (HDR) brachytherapy treatments. Due to self-absorption and oblique filtration of radiation in the source capsule material, an inherent anisotropy is present in the dose distribution around the source which can be described by a measurable two-dimensional anisotropy function, F(r, θ).

Materials and methods

Measurements were carried out in a specially designed and locally fabricated PMMA phantom with provisions to accommodate miniature LiF TLD rods and EBT2 film dosimeters at identical radial distances with respect to the 192Ir source.

Results

The data of anisotropy function generated by the use of the Gafchromic EBT2 film method are in agreement with their TLD measured values within 4%. The produced data are also consistent with their experimental and Monte Carlo calculated results for this source available in the literature.

Conclusion

Gafchromic EBT2 film was found to be a feasible dosimeter in determining anisotropy in the dose distribution of 192Ir source. It offers high resolution and is a viable alternative to TLD dosimetry at discrete points. The method described in this paper is useful for comparing the performances of detectors and can be applied for other brachytherapy sources as well.  相似文献   

4.
PurposeTo assess the radiation dose to the fetus of a pregnant patient undergoing high-dose-rate (HDR) 192Ir interstitial breast brachytherapy, and to design a new patient setup and lead shielding technique that minimizes the fetal dose.MethodsRadiochromic films were placed between the slices of an anthropomorphic phantom modeling the patient. The pregnant woman was seated in a chair with the breast over a table and inside a leaded box. Dose variation as a function of distance from the implant volume as well as dose homogeneity within a representative slice of the fetal position was evaluated without and with shielding.ResultsWith shielding, the peripheral dose after a complete treatment ranged from 50 cGy at 5 cm from the caudal edge of the breast to <0.1 cGy at 30 cm. The shielding reduces absorbed dose by a factor of two near the breast and more than an order of magnitude beyond 20 cm. The dose is heterogeneous within a given axial plane, with variations from the central region within 50%. Interstitial HDR 192Ir brachytherapy with breast shielding can be more advantageous than external-beam radiotherapy (EBRT) from a radiation protection point of view, as long as the distance to the uterine fundus is higher than about 10 cm. Furthermore, the weight of the shielding here proposed is notably lower than that needed in EBRT.ConclusionsShielded breast brachytherapy may benefit pregnant patients needing localized radiotherapy, especially during the early gestational ages when the fetus is more sensitive to ionizing radiation.  相似文献   

5.
PurposeTo investigate dose perturbations created by high-atomic number (Z) materials in high dose rate (HDR) Iridium-192 (192Ir) treatment region.Methods and materialsA specially designed parallel plate ion chamber with 5 μm thick window was used to measure the dose rates from 192Ir source downstream of the high-Z materials. A Monte Carlo (MC) code was employed to calculate the dose rates in both upstream and downstream of the high-Z interfaces at distances ranging from 0.01 to 2 mm. The dose perturbation factor (DPF) was defined as the ratio of dose rate with and without high-Z material in a water phantom. For verifying the Z dependence, both 0.1- and 1.0 mm-thick sheets of Pb, Au, Ta, Sn, Cu, Fe, Ti and Al were used.Results/conclusionsThe DPF depends on the Z and thickness of layer. At the downstream of a 0.1 mm layer of Pb, Au, Ta, Sn, Cu, Fe, Ti and Al, the DPF by MC were 3.73, 3.42, 3.04, 1.71, 1.04, 0.98, 0.92, or 0.94 respectively. When Z is greater than or equal to 50, the MC and experimental results disagree significantly (>20%) due to large DPF gradient but are in agreement for Z less than or equal to 29. Thin layers of Z greater than or equal to 50 near a 192Ir source in water produce significant dose perturbations (i.e. increases) in the vicinity of the medium-high-Z interfaces and may thus cause local over-dose in 192Ir brachytherapy. Conversely, this effect may potentially be used to deliver locally higher doses to targeted tissue.  相似文献   

6.
Several malignant tumors and fibrotic diseases are associated with PDGFRβ overexpression and excessive signaling, making this receptor attractive for molecular targeting and imaging approaches. A series of benzo[d]imidazole-quinoline derivatives were designed and synthesized to develop radioiodinated compounds as PDGFRβ-specific imaging probes. The structure activity relationship (SAR) evaluation of the designed compounds was performed. Among them, 2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]-8-(piperazin-1-yl)quinoline (5a) and 4-{2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}morpholine (5d) exhibited a relatively high PDGFRβ-TK inhibitory potency, whereas iodinated 5a derivative 5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]-8-(piperazin-1-yl)quinoline (8) exhibited a superior inhibitory potency as PDGFRβ inhibitor than iodinated 5d derivative 4-{5-iodo-2-[5-(2-methoxyethoxy)-1H-benzo[d]imidazol-1-yl]quinolin-8-yl}morpholine (11). Furthermore, [125I]8 and [125I]11 were synthesized and evaluated for PDGFRβ radioligand ability, both in vitro and in vivo. Cellular uptake experiments showed that [125I]8 had a higher uptake in BxPC3-luc cells as PDGFRβ-positive cells than [125I]11. Incubation of [125I]8 after pretreatment of PDGFRβ ligands significantly reduced the uptake of [125I]8. In biodistribution experiments using tumor-bearing mice, [125I]8 accumulation in the tumor 1?h postinjection was higher than that of the benzo[d]imidazol-quinoline derivative [125I]IIQP, used in our previous research. These results indicate that [125I]8 could be a promising PDGFRβ imaging agent. Although its clinical application requires further structural modifications, the results obtained in this research may be useful for the development of PDGFRβ-specific radioligands.  相似文献   

7.
In this report, we present a rapid and highly efficient method for radioactive iodine labeling of trans-cyclooctene group conjugated biomolecules using inverse-electron-demand Diels–Alder reaction. Radioiodination reaction of the tetrazine structure was carried out using the stannylated precursor 2 to give 125I-labeled product ([125I]1) with high radiochemical yield (65 ± 8%) and radiochemical purity (>99%). For radiolabeling application of [125I]1, trans-cyclooctene derived cRGD peptide and human serum albumin were prepared. These substrates were reacted with [125I]1 under mild condition to provide the radiolabeled products [125I]6 and [125I]8, respectively, with excellent radiochemical yields. The biodistribution study of [125I]8 in normal ICR mice showed significantly lower thyroid uptake values than that of 125I-labeled human serum albumin prepared by a traditional radiolabeling method. Therefore [125I]8 will be a useful radiolabeled tracer in various molecular imaging and biological studies. Those results clearly demonstrate that [125I]1 will be used as a valuable prosthetic group for radiolabeling of biomolecules.  相似文献   

8.
In this study, the benzimidazole derivatives were synthesized and evaluated as imaging agents for the NR2B subtype of NMDA receptor. Among these ligands, 2-{[4-(4-iodobenzyl)piperidin-1-yl]methyl}benzimidazol-5-ol (8) and N-{2-[4-(4-iodobenzyl)-piperidin-1-ylmethyl]benzoimidazol-5-yl}-methanesulfonamide (9) exhibited high affinity for the NR2B subunit (Ki values; 7.28 nM for 8 and 5.75 nM for 9). In vitro autoradiography experiments demonstrated high accumulation in the forebrain regions but low in the cerebellum for both [125I]8 and [125I]9. These regional distributions of the radioligands correlated with the expression of the NR2B subunit. The in vitro binding of these ligands was inhibited by NR2B antagonist but not by other site ligands, which suggested the high selectivity of [125I]8 and [125I]9 for the NR2B subunit. In mice, the regional brain uptakes of [125I]8 and [125I]9 at 5–180 min after administration were 0.42–0.56% and 0.44–0.67% dose/g, respectively. The brain-to-blood ratio of [125I]8 at 180 min was reduced by 34% in the presence of non-radioactive ligands and by 59% in the presence of the NR2B ligand Ro-25,6981. These results indicated that [125I]8 could be partially bound to the NR2B subunit in vivo. Although the brain uptake of these benzimidazole derivatives was too low to allow for in vivo SPECT imaging, these compounds might be useful scaffolds for the development of imaging probes specific for the NMDA receptors.  相似文献   

9.
Radioligand therapy (RLT) using prostate-specific membrane antigen (PSMA) targeting ligands is an attractive option for the treatment of Prostate cancer (PCa) and its metastases. We report herein a series of radioiodinated glutamate-urea-lysine-phenylalanine derivatives as new PSMA ligands in which l-tyrosine and l-glutamic acid moieties were added to increase hydrophilicity concomitant with improvement of in vivo targeting properties. Compounds 8, 15, 19a/19b and 23a/23b were synthesized and radiolabeled with 125I by iododestannylation. All iodinated compounds displayed high binding affinities toward PSMA (IC50 = 1–13 nM). In vitro cell uptake studies demonstrated that compounds containing an l-tyrosine linker moiety (8, 15 and 19a/19b) showed higher internalization than MIP-1095 and 23a/23b, both without the l-tyrosine linker moiety. Biodistribution studies in mice bearing PC3-PIP and PC3 xenografts showed that [125I]8 and [125I]15 with higher lipophilicity exhibited higher nonspecific accumulations in the liver and intestinal tract, whereas [125I]19a/19b and [125I]23a/23b containing additional glutamic acid moieties showed higher accumulations in the kidney and implanted PC3-PIP (PSMA+) tumors. [125I]23b displayed a promising biodistribution profile with favorable tumor retention, fast clearance from the kidney, and 2–3-fold lower uptake in the liver and blood than that observed for [125I]MIP-1095. [125/131I]23b may serve as an optimal PSMA ligand for radiotherapy treatment of prostate cancer over-expressing PSMA.  相似文献   

10.
11.
AimThe purpose of this study is to calculate radiation dose around a brachytherapy source in a water phantom for different seed locations or rotation the sources by the matrix summation method.BackgroundMonte Carlo based codes like MCNP are widely used for performing radiation transport calculations and dose evaluation in brachytherapy. But for complicated situations, like using more than one source, moving or rotating the source, the routine Monte Carlo method for dose calculation needs a long time running.Materials and methodsThe MCNPX code has been used to calculate radiation dose around a 192Ir brachytherapy source and saved in a 3D matrix. Then, we used this matrix to evaluate the absorbed dose in any point due to some sources or a source which shifted or rotated in some places by the matrix summation method.ResultsThree dimensional (3D) dose results and isodose curves were presented for 192Ir source in a water cube phantom shifted for 10 steps and rotated for 45 and 90° based on the matrix summation method. Also, we applied this method for some arrays of sources.ConclusionThe matrix summation method can be used for 3D dose calculations for any brachytherapy source which has moved or rotated. This simple method is very fast compared to routine Monte Carlo based methods. In addition, it can be applied for dose optimization study.  相似文献   

12.

Aim

The aim of this study is to evaluate the dose distribution of the Flexisource 192Ir source.

Background

Dosimetric evaluation of brachytherapy sources is recommended by task group number 43 (TG. 43) of American Association of Physicists in Medicine (AAPM).

Materials and methods

MCNPX code was used to simulate Flexisource 192Ir source. Dose rate constant and radial dose function were obtained for water and soft tissue phantoms and compared with previous data on this source. Furthermore, dose rate along the transverse axis was obtained by simulation of the Flexisource and a point source and the obtained data were compared with those from Flexiplan treatment planning system (TPS).

Results

The values of dose rate constant obtained for water and soft tissue phantoms were equal to 1.108 and 1.106, respectively. The values of the radial dose function are listed in the form of tabulated data. The values of dose rate (cGy/s) obtained are shown in the form of tabulated data and figures. The maximum difference between TPS and Monte Carlo (MC) dose rate values was 11% in a water phantom at 6.0 cm from the source.

Conclusion

Based on dosimetric parameter comparisons with values previously published, the accuracy of our simulation of Flexisource 192Ir was verified. The results of dose rate constant and radial dose function in water and soft tissue phantoms were the same for Flexisource and point sources. For Flexisource 192Ir source, the results of TPS calculations in a water phantom were in agreement with the simulations within the calculation uncertainties. Furthermore, the results from the TPS calculation for Flexisource and MC calculation for a point source were practically equal within the calculation uncertainties.  相似文献   

13.
High dose rate brachytherapy (HDR) using 192Ir sources is well accepted as an important treatment option and thus requires an accurate dosimetry standard. However, a dosimetry standard for the direct measurement of the absolute dose to water for this particular source type is currently not available. An improved standard for the absorbed dose to water based on Fricke dosimetry of HDR 192Ir brachytherapy sources is presented in this study. The main goal of this paper is to demonstrate the potential usefulness of the Fricke dosimetry technique for the standardization of the quantity absorbed dose to water for 192Ir sources. A molded, double-walled, spherical vessel for water containing the Fricke solution was constructed based on the Fricke system. The authors measured the absorbed dose to water and compared it with the doses calculated using the AAPM TG-43 report. The overall combined uncertainty associated with the measurements using Fricke dosimetry was 1.4% for k = 1, which is better than the uncertainties reported in previous studies. These results are promising; hence, the use of Fricke dosimetry to measure the absorbed dose to water as a standard for HDR 192Ir may be possible in the future.  相似文献   

14.
In this study, six novel benzothiazole derivatives based on the bithiophene structure were developed as potential β-amyloid probes. In vitro binding studies using Aβ aggregates showed that all of them demonstrated high binding affinities with Ki values ranged from 0.11 to 4.64 nM. In vitro fluorescent staining results showed that these compounds can intensely stained Aβ plaques within brain sections of APP/PS1 transgenic mice, animal model for AD. Two radioiodinated compounds [125I]-2-(5′-iodo-2,2′-bithiophen-5-yl)-6-methoxybenzo[d]thiazole [125I]10 and [125I]-2-(2,2′-bithiophen-5-yl)-6-iodobenzo[d]thiazole [125I]13 were successfully prepared through an iododestannylation reaction. Furthermore, in vitro autoradiography of the AD model mice brain sections showed that both [125I]10 and [125I]13 labeled the Aβ plaques specifically with low background. In vivo biodistribution studies in normal mice indicated that [125I]13 exhibited high brain uptake (3.42% ID/g at 2 min) and rapid clearance from the brain (0.53% ID/g at 60 min), while [125I]10 showed lower brain uptake (0.87% ID/g at 2 min). In conclusion, these preliminary results of this study suggest that the novel radioiodinated benzothiazole derivative [125I]13 may be a candidate as an in vivo imaging agent for detecting β-amyloid plaques in the brain of AD patients.  相似文献   

15.
We report radioiodinated chalcone derivatives as new SPECT imaging probes for amyloid β (Aβ) plaques. The monoethyleneoxy derivative 2 and allyloxy derivative 8 showed a high affinity for Aβ(1–42) aggregates with Ki values of 24 and 4.5 nM, respectively. Fluorescent imaging demonstrated that 2 and 8 clearly stained thioflavin-S positive Aβ plaques in the brain sections of Tg2576 transgenic mice. In vitro autoradiography revealed that [125I]2 displayed no clear accumulation toward Aβ plaques in the brain sections of Tg2576 mice, whereas the accumulation pattern of [125I]8 matched with the presence of Aβ plaques both in the brain sections of Tg2576 mice and an AD patient. In biodistribution studies using normal mice, [125I]2 showed preferable in vivo pharmacokinetics (4.82%ID/g at 2 min and 0.45%ID/g at 60 min), while [125I]8 showed only a modest brain uptake (1.62%ID/g at 2 min) with slow clearance (0.56%ID/g at 60 min). [125I]8 showed prospective binding properties for Aβ plaques, although further structural modifications are needed to improve the blood brain barrier permeability and washout from brain.  相似文献   

16.
Purpose: There is a widespread belief in the cardiology and radiation oncology community that high dose rate 192Ir intravascular brachytherapy cannot be implemented without massive additional shielding of the conventional catheterization labs. The purpose of this work is to show that this is a myth, which is not based on sound radiation protection principles.Methods: Exposure rates in air were calculated for a variety of point and line sources of 192Ir. Exposures per treatment at different distances from the source were calculated for a typical intravascular brachytherapy treatment of a 15-Gy dose at a radial distance of 2 mm from the source and for source lengths in the range of 0 to 10 cm. Additionally, exposure rates outside the catheterization lab were calculated for various lead shielding thicknesses typical of conventional X-ray facilities. These rates were used along with the NCRP recommendations on radiation facility design to assess shielding requirements.Results: For a treatment dose of 15 Gy at 2 mm, the occupational exposure per treatment at 2 m in air without any tissue attenuation or shielding was 7.8 mR for a lesion length of 3.0 cm. This exposure/treatment is independent of the dose rate or the activity of the source. However, it increases as lesion length is increased, increasing from 5.4 to 24.9 mR as lesion length increased from 2 to 10 cm. Exposures in unrestricted areas outside the catheterization lab using the NCRP shielding rationale can be kept below 2 mR per treatment and using appropriate workload, use, and occupancy factors below 2 mR per week.Conclusions: The feasibility of implementing a high dose rate 192Ir intravascular brachytherapy program in a catheterization laboratory is totally independent of the dose rate or the activity of the source. If it is feasible to implement 192Ir brachytherapy in a conventional catheterization lab using low activity 192Ir seeds, then it is also feasible to do so with a high activity 192Ir afterloader.  相似文献   

17.
18.
There is strong interest to study the involvement of brain cannabinoid subtype-1 (CB1) receptors in neuropsychiatric disorders with single photon emission computed tomography (SPECT) and a suitable radioligand. Here we report the synthesis of a novel high-affinity radioiodinated CB1 receptor ligand ([125I]8, [125I]1-(2-iodophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxylate, [125I]SD7015). By autoradiography in vitro, [125I]8 showed selective binding to CB1 receptors on human brain postmortem cryosections and now merits labeling with iodine-123 for further evaluation as a SPECT radioligand in non-human primate.  相似文献   

19.
[125I]IodoDPA-713 [125I]1, which targets the translocator protein (TSPO, 18 kDa), was synthesized in seven steps from methyl-4-methoxybenzoate as a tool for quantification of inflammation in preclinical models. Preliminary in vitro autoradiography and in vivo small animal imaging were performed using [125I]1 in a neurotoxicant-treated rat and in a murine model of lung inflammation, respectively. The radiochemical yield of [125I]1 was 44 ± 6% with a specific radioactivity of 51.8 GBq/μmol (1400 mCi/μmol) and >99% radiochemical purity. Preliminary studies showed that [125I]1 demonstrated increased specific binding to TSPO in a neurotoxicant-treated rat and increased radiopharmaceutical uptake in the lungs of an experimental inflammation model of lung inflammation. Compound [125I]1 is a new, convenient probe for preclinical studies of TSPO activity.  相似文献   

20.
PurposeThe purpose of the present study was to perform an independent calculation of dosimetric parameters associated with a new 192Ir brachytherapy source model, IRAsource.Materials and methodsThe parameters of air kerma strength (AKS), dose rate constant (DRC), geometry function (GF), radial dose function (RDF), as well as two-dimensional (2D) anisotropy function (AF) of IRAsource 192Ir source model were calculated in this study. The MC n-particle extended (MCNPX) code was also employed for simulating high dose rate (HDR), IRAsource and 192Ir source; and formalism was used for calculating dosimetry parameters based on task group number 43 updated report (TG-43 U1).ResultsThe results of this study were consistent with the ones reported about the IRAsource source by Sarabiasl et al. The AKS per 1 mCi activity and the DRC values were also equal to 3.65 cGycm2 h–1 mCi–1 and 1.094 cGyh–1U–1; respectively. The comparison of the results of the DRC and the RDF reported by Sarabiasl et al. also validated the 192Ir IRAsource simulation in this study. Moreover, the AFs of IRAsource source model were in a good agreement with those of Sarabiasl et al. at different distances, which could be attributed to identical geometries.ConclusionIn line with those reported by Sarabiasl et al., the results of this study confirmed the IRAsource 192Ir source for clinical uses. The calculated dosimetric parameters of the IRAsource source could be utilized in clinical practices as input data sets or for validation of treatment planning system calculations.  相似文献   

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