ABSTRACT
Excitons in Bridgman grown halide perovskite CsPbBr3 single crystals were examined using photoluminescence (PL) spectroscopy to determine the nature of the electronic states. The photoluminescence intensity was strongly temperature-dependent and depended upon the specific exciton band. At low temperatures intrinsic disorder and its related shallow below bandgap tail states determine the emission properties. Photoluminescence at low temperature revealed the presence of several strong bands at the band edge that is attributed to free or trapped/bound excitons. This PL emission results from strong electron-phonon coupling with an average phonon energy Eph of 6.5 and 27.4 meV for the emissions, comparable to that observed in other perovskites. The Huang-Rhys parameter S was calculated to be 3.81 and 1.51, indicating strong electron-phonon coupling. The interactions between electrons and phonons produce small polarons that tend to bind charge carriers and result in trapped/bound excitons. The transient photoluminescence response of each specific band was studied, and the results indicated a multiphonon recombination process. Average PL lifetimes of â¼17 ns for free excitons and â¼38 ns for trapped/bound excitons were determined. The observed edge states could be associated with native defects such as vacancies and interstitials, as well as twinning due to the cubic-to-tetragonal phase transition in CsPbBr3. Elimination of the trapping sites for binding excitons could lead to improved charge transport mobilities, carrier lifetimes, and detector properties in this system.
ABSTRACT
AIM: To determine the effect of pioglitazone treatment on in vivo and ex vivo muscle mitochondrial function in a rat model of diabetes. METHODS: Both the lean, healthy rats and the obese, diabetic rats are Zucker Diabetic Fatty (ZDF) rats. The homozygous fa/fa ZDF rats are obese and diabetic. The heterozygous fa/+ ZDF rats are lean and healthy. Diabetic Zucker Diabetic Fatty rats were treated with either pioglitazone (30 mg/kg/day) or water as a control (n = 6 per group), for 2 weeks. In vivo ¹H and ³¹P magnetic resonance spectroscopy was performed on skeletal muscle to assess intramyocellular lipid (IMCL) content and muscle oxidative capacity, respectively. Ex vivo muscle mitochondrial respiratory capacity was evaluated using high-resolution respirometry. In addition, several markers of mitochondrial content were determined. RESULTS: IMCL content was 14-fold higher and in vivo muscle oxidative capacity was 26% lower in diabetic rats compared with lean rats, which was, however, not caused by impairments of ex vivo mitochondrial respiratory capacity or a lower mitochondrial content. Pioglitazone treatment restored in vivo muscle oxidative capacity in diabetic rats to the level of lean controls. This amelioration was not accompanied by an increase in mitochondrial content or ex vivo mitochondrial respiratory capacity, but rather was paralleled by an improvement in lipid homeostasis, that is lowering of plasma triglycerides and muscle lipid and long-chain acylcarnitine content. CONCLUSION: Diminished in vivo muscle oxidative capacity in diabetic rats results from mitochondrial lipid overload and can be alleviated by redirecting the lipids from the muscle into adipose tissue using pioglitazone treatment.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Lipid Metabolism/drug effects , Mitochondrial Diseases/prevention & control , Muscle, Skeletal/drug effects , Oxidative Stress/drug effects , Thiazolidinediones/therapeutic use , Animals , Biomarkers/metabolism , Carnitine/analogs & derivatives , Carnitine/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Hypertriglyceridemia/complications , Hypertriglyceridemia/prevention & control , Hypoglycemic Agents/adverse effects , Hypolipidemic Agents/therapeutic use , Male , Mitochondria, Muscle/drug effects , Mitochondria, Muscle/metabolism , Mitochondrial Diseases/complications , Mitochondrial Turnover/drug effects , Muscle, Skeletal/metabolism , Obesity/complications , Oxidative Phosphorylation/drug effects , PPAR gamma/antagonists & inhibitors , Pioglitazone , Rats, Zucker , Thiazolidinediones/adverse effectsABSTRACT
The process of "clinical reasoning" is exemplified as supportive to the complaint management of the Statutory Medical Health Advisory Board in Lower Saxony, Germany, within the operational division for long-term care insurance. A model case from real life illustrates in detail the hypothetical-deductive approach by Beusheusen and Klemme/Siegmann. Because of the potential area of conflicts between human concern in the case of a long-term care burden and legal requirements, the process was analysed in terms of a pragmatic reasoning. Human resources of the claimant and persons in charge at customer's service were demonstrated as well as political, statutory and institutional determining factors. Concluding self-perception validates the process in the context of evidence-based practice.
Subject(s)
Dissent and Disputes , Long-Term Care/organization & administration , Models, Organizational , National Health Programs/organization & administration , Negotiating/methods , Patient Satisfaction , Germany , Humans , Organizational Case StudiesABSTRACT
The hypothesis was tested that the variation of in vivo glycolytic flux with contraction frequency in skeletal muscle can be qualitatively and quantitatively explained by calcium-calmodulin activation of phosphofructokinase (PFK-1). Ischemic rat tibialis anterior muscle was electrically stimulated at frequencies between 0 and 80 Hz to covary the ATP turnover rate and calcium concentration in the tissue. Estimates of in vivo glycolytic rates and cellular free energetic states were derived from dynamic changes in intramuscular pH and phosphocreatine content, respectively, determined by phosphorus magnetic resonance spectroscopy ((31)P-MRS). Computational modeling was applied to relate these empirical observations to understanding of the biochemistry of muscle glycolysis. Hereto, the kinetic model of PFK activity in a previously reported mathematical model of the glycolytic pathway (Vinnakota KC, Rusk J, Palmer L, Shankland E, Kushmerick MJ. J Physiol 588: 1961-1983, 2010) was adapted to contain a calcium-calmodulin binding sensitivity. The two main results were introduction of regulation of PFK-1 activity by binding of a calcium-calmodulin complex in combination with activation by increased concentrations of AMP and ADP was essential to qualitatively and quantitatively explain the experimental observations. Secondly, the model predicted that shutdown of glycolytic ATP production flux in muscle postexercise may lag behind deactivation of PFK-1 (timescales: 5-10 s vs. 100-200 ms, respectively) as a result of accumulation of glycolytic intermediates downstream of PFK during contractions.
Subject(s)
Glycolysis/physiology , Muscle, Skeletal/metabolism , Adenosine Triphosphate/metabolism , Animals , Calcium/analysis , Calcium/metabolism , Calmodulin/chemistry , Calmodulin/metabolism , Computer Simulation , Hydrogen-Ion Concentration , Ischemia/metabolism , Magnetic Resonance Spectroscopy/methods , Male , Models, Biological , Muscle Contraction/physiology , Phosphocreatine/analysis , Phosphocreatine/metabolism , Phosphofructokinase-1, Muscle Type/chemistry , Phosphofructokinase-1, Muscle Type/metabolism , Physical Conditioning, Animal/physiology , Rats , Rats, WistarABSTRACT
PURPOSE: To determine if a rotated collimator on an Elekta Synergy-S with Beam Modulator MLC (BMx) allows for dosimetrically acceptable treatment of targets exceeding the length of the maximum field size (21×16cm). The BMx is a high-resolution MLC with 4mm leaves but is of limited clinical use on patient target volumes exceeding 20cm in length. Rotation of the collimator utilizes the Pythagorean geometry to extend treatment length. This potentially increases the length of the PTV that be conformally treated. METHODS: Rods of 21-23cm length were contoured in water with the Pinnacle treatment planning system. The width of the rods varies from 1 -5cm. Four isocentric treatment plans were generated for each target: four-field conformal, 7-field IMRT, single-arc VMAT, and a modified double-arc VMAT (MDAV), with the collimator angled at 55°. The MDAV method consists of two opposing 180° arcs with the collimator turned 55° in opposite directions. A successful plan is defined as 99% of the target volume being covered by a minimum of 95% of the prescribed dose. Conformality is determined as a ratio of the volume exposed to prescribed isodose and target volume. RESULTS: Targets of length 21cm, 22cm, and 23 cm are able to be treated with widths of 4cm, 5 cm, and 4cm respectively. The MDAV method achieves these results on all trials. The VMAT method achieves these results for the 21cm and 23cm long target. The IMRT Method achieves these results for the 21cm long target. With the exception of the 1cm wide targets, the average conformality is approximately 2.5. CONCLUSIONS: Changing the collimator angle of the BMx Elekta-S machine allows for a 3cm length increase of targets up to 5cm. Further work will assess clinical suitability of these findings for treatment of head and neck tumors and spinal masses.
ABSTRACT
PURPOSE: Direct addition of doses between plans with different fractionation fails to provide accurate dose-response information to anticipate clinical outcome. To combine different fractionation patterns, first-order biological model correction for dose-rate must be included. Moreover, 3-D isoeffect patterns of the combined doses must be displayed so that overlap area to elegant volumes can be avoided. The linear quadratic (LQ) model and biologically effective dose (BED) method were used to produce a combined plan in equivalent 2 Gy fractions (EQD2) for radiosurgery and conventional 3D radiotherapy. METHODS: For patients with multiple courses of radiotherapy, dose distributions of the prior and boost treatment plans were converted to BED. The fraction size specified by the prescription was applied globally for each BED calculation, α/ß ratio of 10 and 2.5 was used for early and late effect, respectively. Image registration with CT or MR was performed for initial and boost plans. The registration information was applied to dose distributions to obtain the composite EQD2. RESULTS: As a demonstration of this method, two patients were selected who had combined treatments from substantially different modalities. A patient with liver cancer initially received radiotherapy of 30 Gy/10 Fx and re-irradiation with CyberKnife radiosurgery (15 Gy/1 Fx). The combined plan showed that the PTV received EQD2 of 63.8 Gy. Another patient had brain metastasis treated with GammaKnife of 18 Gy (50% isodose) followed by conventional 3D whole brain radiation of 30 Gy/10 Fx. The minimal combined tumor EQD2 was 74.5 Gy. Early and late calculated responses showed that all critical organ doses were within tolerance. CONCLUSIONS: For patients receiving radiation with different fractionation schemes, combined isoeffective dose distributions were calculated and displayed. In both cases, crucial information regarding 3-D dose distributions assisted the physicians in determining whether tolerance limits of overlap areas of retreated critical structures were preserved.
ABSTRACT
We have demonstrated the first bipolar magnetic junction transistor using a dilute magnetic semiconductor. For an InMnAs p-n-p transistor magnetoamplification is observed at room temperature. The observed magnetoamplification is attributed to the magnetoresistance of the magnetic semiconductor InMnAs heterojunction. The magnetic field dependence of the transistor characteristics confirm that the magnetoamplification results from the junction magnetoresistance. To describe the experimentally observed transistor characteristics, we propose a modified Ebers-Moll model that includes a series magnetoresistance attributed to spin-selective conduction. The capability of magnetic field control of the amplification in an all-semiconductor transistor at room temperature potentially enables the creation of new computer logic architecture where the spin of the carriers is utilized.
ABSTRACT
The Medical Internal Radiation Dose Committee (MIRD) formalism assumes reference mass values for the organs (source and target) and the total body. MIRD publication 11 provides guidance on how patient-specific scaling of reference radionuclide S-values are to be performed for the electron component of the emission spectrum. However, guidance on patient-specific scaling of the photon contributions to the S-value is given only for those cases where the source and target organs are either far apart or are the same. The photon component of the S-value is derived from photon-Specific Absorbed Fractions (SAFs). These are obtained by Monte Carlo calculation of photon transport. The objective of this work is to verify the MIRD 11 guidance and to examine the relationship between photon SAFs and source/target organ mass when the conditions listed above do not apply. Furthermore, the scaling for photon cross-dose to distributed organs is at present not defined due to lack of data for models other than the reference model. The validity of mass scaling for cross irradiation from near and distant photons sources, especially for Red Bone Marrow (RBM) as a target tissue is also investigated. This is achieved by comparing Monte Carlo-derived SAFs for different source organs to RBM across the GSF voxel phantom series. The results show that, for photon energies greater than 100 keV, the SAF of most source organs to RBM need not be corrected for target mass (error < 5%). In contrast to the results obtained for well-defined source organs, the SAF for RBM irradiating RBM gives a deviation of up to 16% across the different GSF voxel phantoms.
Subject(s)
Models, Biological , Radioisotopes/pharmacokinetics , Whole-Body Counting/methods , Whole-Body Counting/standards , Biological Assay/methods , Biological Assay/standards , Computer Simulation , Humans , Internationality , Organ Specificity , Radiation Dosage , Reference Values , Relative Biological Effectiveness , Sensitivity and Specificity , Species Specificity , Tissue DistributionABSTRACT
A BaTiO3 thin-film electro-optic waveguide modulator with a low half-wave voltage-length product has been demonstrated at near-infrared wavelengths of 1-1.6 microm. Half-wave voltage-length products as small as 0.25 and 0.5 V cm were measured for a 5-mm-long device at wavelengths of 973 and 1561 nm, respectively. The effective electro-optic coefficients were calculated as 420 pm/V at 973 nm and 360 pm/V at 1561 nm. Further improvements in device performance by optimizing the ferroelectric domain structure are anticipated.
ABSTRACT
The high frequency operation of a low-voltage electrooptic modulator based on a strip-loaded BaTiO3 thin film waveguide structure has been demonstrated. The epitaxial BaTiO3 thin film on an MgO substrate forms a composite structure with a low effective dielectric constant of 20.8 at 40 GHz. A 3.9 V half-wave voltage with a 3.7 GHz 3-dB bandwidth and a 150 pm/V effective electrooptic coefficient is obtained for the 3.2mm-long modulator at 1.55 ?m. Broadband modulation up to 40 GHz is measured with a calibrated detection system. Numerical simulations indicate that the BaTiO3 thin film modulator has the potential for a 3-dB operational bandwidth in excess of 40 GHz through optimized design.
ABSTRACT
In radiosurgery, conformity indices are often used to compare competing plans, evaluate treatment techniques, and assess clinical complications. Several different indices have been reported to measure the conformity of the prescription isodose to the target volume. The PITV recommended in the Radiation Therapy Oncology Group (RTOG) radiosurgery guidelines, defined as the ratio of the prescription isodose volume (PI) over the target volume (TV), is probably the most frequently quoted. However, these currently used conformity indices depend on target size and shape complexity. The objectives of this study are to systematically investigate the influence of target size and shape complexity on existing conformity indices, and to propose a different conformity index-the conformity distance index (CDI). The CDI is defined as the average distance between the target and the prescription isodose line. This study examines five case groups with volumes of 0.3, 1.0, 3.0, 10.0, and 30.0 cm(3). Each case group includes four simulated shapes: a sphere, a moderate ellipsoid, an extreme ellipsoid, and a concave "C" shape. Prescription dose coverages are generated for three simplified clinical scenarios, i.e., the PI completely covers the TV with 1 and 2 mm margins, and the PI over-covers one half of the TV with a 1 mm margin and under-covers the other half with a 1 mm margin. Existing conformity indices and the CDI are calculated for these five case groups as well as seven clinical cases. When these values are compared, the RTOG PITV conformity index and other similar conformity measures have much higher values than the CDI for smaller and more complex shapes. With the same quality of prescription dose coverage, the CDI yields a consistent conformity measure. For the seven clinical cases, we also find that the same PITV values can be associated with very different conformity qualities while the CDI predicts the conformity quality accurately. In summary, the proposed CDI provides more consistent and accurate conformity measurements for all target sizes and shapes studied, and therefore will be a more useful conformity index for irregularly shaped targets.
Subject(s)
Quality Assurance, Health Care/methods , Radiosurgery/standards , Radiotherapy Planning, Computer-Assisted/standards , Computer Simulation , Databases, Factual , Humans , Mathematical Computing , Radiotherapy Dosage , Radiotherapy, Conformal/standardsABSTRACT
PURPOSE: We have previously presented a technique that fuses ProstaScint and pelvic CT images for the purpose of designing brachytherapy that targets areas at high risk for treatment failure. We now correlate areas of increased intensity seen on ProstaScint-CT fusion images to biopsy results in a series of 7 patients to evaluate the accuracy of this technique in localizing intraprostatic disease. METHODS AND MATERIALS: The 7 patients included in this study were evaluated between June 1998 and March 29, 1999 at Metrohealth Medical Center and University Hospitals of Cleveland in Cleveland, Ohio. ProstaScint and CT scans of each patient were obtained before transperineal biopsy and seed implantation. Each patient's prostate gland was biopsied at 12 separate sites determined independently of Prostascint-CT scan results. RESULTS: When correlated with biopsy results, our method yielded an overall accuracy of 80%: with a sensitivity of 79%, a specificity of 80%, a positive predictive value of 68%, and a negative predictive value of 88%. CONCLUSION: The image fusion of the pelvic CT scan and ProstaScint scan helped identify foci of adenocarcinoma within the prostate that correlated well with biopsy results. These data may be useful to escalate doses in regions containing tumor by either high-dose rate or low-dose rate brachytherapy, as well as by external beam techniques such as intensity modulated radiotherapy (IMRT).
Subject(s)
Adenocarcinoma/diagnostic imaging , Antibodies, Monoclonal , Indium Radioisotopes , Prostatic Neoplasms/diagnostic imaging , Radioimmunodetection/methods , Adenocarcinoma/pathology , Biopsy , Humans , Male , Prospective Studies , Prostate/diagnostic imaging , Prostate/pathology , Prostatic Neoplasms/pathology , Sensitivity and Specificity , Tomography, X-Ray Computed/methodsABSTRACT
Hematologic toxicity limits the radioactivity that may be administered for radiolabeled antibody therapy. This work examines approaches for obtaining biodistribution data and performing dosimetry when the administered antibody is known to bind to a cellular component of blood, bone, or marrow. Marrow dosimetry in this case is more difficult because the kinetics of antibody clearance from the blood cannot be related to the marrow. Several approaches for obtaining antibody kinetics in the marrow are examined and evaluated. The absorbed fractions and S factors that should be used in performing marrow dosimetry are also examined and the effect of including greater anatomical detail is considered. The radiobiology of the red marrow is briefly reviewed. Recommendations for performing marrow dosimetry when the antibody binds to the marrow are provided.
Subject(s)
Blood/radiation effects , Bone Marrow/radiation effects , Bone and Bones/radiation effects , Radioisotopes/pharmacokinetics , Radiometry/methods , Bone Marrow/physiology , Humans , Kinetics , Models, Theoretical , Phantoms, Imaging , Radionuclide Imaging , Reproducibility of ResultsABSTRACT
As more radionuclide therapies move from laboratory feasibility studies into clinical reality, it becomes increasingly important for the labeling chemistry to produce consistently a stable radiopharmaceutical that remains intact under the challenge of human catabolism. Similarly, once proof of principle is established to bring a radionuclide conjugate into clinical therapy trials, dosimetric estimates should be made to select the appropriate radionuclide properties, which are based on animal-specific or patient-specific pharmacokinetics and match a set of specific clinical endpoints. These properties may include the radionuclide physical half-life, radiolabeled conjugate biological uptake and clearance, product-specific activity, range and type of emissions, and resultant effects on tumor and normal tissue cellular survival. The immunologist and labeling chemist have now produced a variety of strategies that have potential to increase the therapeutic ratio (tumor-to-normal tissue dose ratio). The advent of normal tissue clearing agents, fragmented or chimerized carriers to improve targeting, and the method of bispecific or two-step and three-step targeting agents has increased the need for realistic modeling of the carrier in vivo to guide prospectively the competitive development of these radiopharmaceuticals. In this article, examples have been taken from the literature to elucidate the benchmark of success that careful experimental design has fostered to bring these agents into clinical practice by creative and logical methodologies.
Subject(s)
Neoplasms/radiotherapy , Radioisotopes/chemistry , Radioisotopes/pharmacology , Half-Life , Humans , Molecular Structure , Radioisotopes/therapeutic useABSTRACT
UNLABELLED: Preliminary evaluations of 125I-labeled Lym-1, an anti-lymphoma mouse IgG2a monoclonal antibody, demonstrated favorable tumor uptake in mice bearing human Burkitt's lymphoma (Raji) tumors. In this study, the pharmacokinetics of 125I- and 131I-Lym-1, and the dosimetry, efficacy, and toxicity of 131I-Lym-1 in Raji-tumored mice were evaluated. METHODS: Lym-1 was radioiodinated by the chloramine-T method and analyzed for monomeric fraction and immunoreactivity (antigen cell binding, relative to unmodified Lym-1). Nude mice bearing Raji tumors (20-500 mm3) received 1.5 MBq (40 microCi) 125I-Lym-1, or 1.5, 7.4, 14.8, or 18.5 MBq (40, 200, 400, or 500 microCi) 131I-Lym-1. Pharmacokinetic data (total body and blood clearance and biodistribution) were used to estimate radiation dosimetry. Mini-thermoluminescent dosimetry (TLD) was also used to measure radiation dosimetry directly for 7 days after injection of 131I-Lym-1. Tumor size, survival, body weight, and blood counts were monitored for 60 days to evaluate therapeutic efficacy and toxicity of 131I-Lym-1. RESULTS: At the time of injection, the mean quality assurance (QA) values for 125I-Lym-1 were 100% monomer and 100% relative immunoreactivity; the corresponding values for 131I-Lym-1 were 73% and 66%, indicating that radiolysis had occurred during the interval between radiolabeling and injection. 125I-Lym-1 exhibited high and sustained concentration in tumors relative to normal organs, whereas 131I-Lym-1 did not. Assuming identical pharmacokinetic behavior to 125I-Lym-1, 131I-Lym-1 would deliver radiation doses of 3.45, 0.83, 1.03, 0.34, and 0.56 Gy per MBq injected (12.8, 3.1, 3.8, 1.3, and 2.1 rad/microCi), to tumor, liver, lungs, total body, and marrow, respectively. When the actual pharmacokinetic data for 131I-Lym-1 (1.5 MBq) were used to estimate dosimetry, corresponding values of 0.51, 0.72, 0.49, 0.31, and 0.41 Gy/MBq (1.9, 2.7, 1.8, 1.1, and 1.5 rad/microCi) were obtained. Similar values were obtained for mice receiving 7.4 or 14.8 MBq of 131I-Lym-1. Similarly, TLD data indicated little preferential radiation dosimetry to tumor. Response rates (cure + CR + PR) for mice receiving 0, 7.4, 14.8, and 18.5 MBq of 131I-Lym-1 were 8%, 7%, 21%, and 45%, respectively. The LD50/30 dose of 131I-Lym-1 was 12.7 MBq (343 microCi). CONCLUSIONS: 125I-Lym-1 exhibited high and sustained concentration in Raji tumors in mice, indicating excellent therapeutic potential for 131I-Lym-1. However, in vitro QA results for 131I-Lym-1 indicated that radiolysis had occurred, and 131I-Lym-1 demonstrated little accumulation in tumor, or preferential radiation dosimetry to tumor in the same model.
Subject(s)
Antibodies, Monoclonal/pharmacokinetics , Antibody Specificity/radiation effects , Burkitt Lymphoma/metabolism , Iodine Radioisotopes/pharmacokinetics , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal, Murine-Derived , Burkitt Lymphoma/radiotherapy , Child , Female , Humans , Iodine Radioisotopes/immunology , Male , Mice , Mice, Nude , Neoplasm Transplantation , Quality Control , Radiation Dosage , Radioimmunotherapy , Radiotherapy Dosage , Survival Analysis , Tumor Cells, CulturedABSTRACT
The purpose of this study was to validate an analytical expression for the absorbed-dose calculation from the spherical source of beta-emitting radionuclides and to apply it to micrometastases treated with radiolabeled monoclonal antibodies. The self-absorbed fractions from I-131 and P-32 uniform spherical sources were calculated using the analytical expression introduced by P. K. Leichner (J. Nucl. Med., 35: 1721-1729, 1994). The calculated absorbed fractions were compared with previously reported values and were found to be in reasonable agreement, with a maximum difference of 15% for smaller masses and a long-range beta emitter. The expression was subsequently applied to estimate the absorbed dose within spheroid models with nonuniform penetration of radiolabeled antibody. The corresponding absorbed dose for I-131 was compared with reported micro-thermoluminescence dosimeter measurements and found to be in good agreement. This work has independently substantiated the methodology outlined by Leichner and may be reliably incorporated into new software developments for radionuclide dosimetry treatment planning.
Subject(s)
Beta Particles , Neoplasm Metastasis/radiotherapy , Radioimmunotherapy , Radiotherapy Dosage , Humans , Iodine Radioisotopes/therapeutic use , Phosphorus Radioisotopes/therapeutic useABSTRACT
Normal liver complications have not been observed in Y-90 microsphere therapy of hepatic tumors [selective internal radiation (SIR)], despite clinical studies reporting estimated absorbed doses to normal liver between 100 and 150 Gy. The purpose of the study was to see whether predictions of normal tissue complication probability (NTCP) models for liver based on clinical data from external beam therapy are consistent with clinical results of SIR. Liver NTCP was calculated using a parallel architecture model and normal liver dose-volume histograms that have been proposed for SIR. A parallel model including internal functional subunit structure is also proposed. Dose rate effects are incorporated. A criterion for comparing model calculations with clinical data is presented. For the parallel architecture model, the predicted NTCP is sensitive to the dose distribution in normal liver and to the model parameters, particularly the repair time. With reasonable assumptions about the microsphere distribution, the parallel model with parameters deduced from external beam therapy outcome analysis is consistent with the observed lack of liver complications. Inclusion of FSU structure widens the range of assumptions under which consistency is found. The parallel model can be consistent with the clinically observed lack of liver complications in SIR. More information about the activity distribution and the radiobiology of normal liver under conditions typical of microsphere therapy should be sought.
Subject(s)
Liver Neoplasms/radiotherapy , Liver/radiation effects , Yttrium Radioisotopes/therapeutic use , Humans , Microspheres , Radiotherapy DosageABSTRACT
This report describes recommended techniques for radiopharmaceutical biodistribution data acquisition and analysis in human subjects to estimate radiation absorbed dose using the Medical Internal Radiation Dose (MIRD) schema. The document has been prepared in a format to address two audiences: individuals with a primary interest in designing clinical trials who are not experts in dosimetry and individuals with extensive experience with dosimetry-based protocols and calculational methodology. For the first group, the general concepts involved in biodistribution data acquisition are presented, with guidance provided for the number of measurements (data points) required. For those with expertise in dosimetry, highlighted sections, examples and appendices have been included to provide calculational details, as well as references, for the techniques involved. This document is intended also to serve as a guide for the investigator in choosing the appropriate methodologies when acquiring and preparing product data for review by national regulatory agencies. The emphasis is on planar imaging techniques commonly available in most nuclear medicine departments and laboratories. The measurement of the biodistribution of radiopharmaceuticals is an important aspect in calculating absorbed dose from internally deposited radionuclides. Three phases are presented: data collection, data analysis and data processing. In the first phase, data collection, the identification of source regions, the determination of their appropriate temporal sampling and the acquisition of data are discussed. In the second phase, quantitative measurement techniques involving imaging by planar scintillation camera, SPECT and PET for the calculation of activity in source regions as a function of time are discussed. In addition, nonimaging measurement techniques, including external radiation monitoring, tissue-sample counting (blood and biopsy) and excreta counting are also considered. The third phase, data processing, involves curve-fitting techniques to integrate the source time-activity curves (determining the area under these curves). For some applications, compartmental modeling procedures may be used. Last, appendices are included that provide a table of symbols and definitions, a checklist for study protocol design, example formats for quantitative imaging protocols, temporal sampling error analysis techniques and selected calculational examples. The utilization of the presented approach should aid in the standardization of protocol design for collecting kinetic data and in the calculation of absorbed dose estimates.
Subject(s)
Radiometry/methods , Radiopharmaceuticals/pharmacokinetics , Humans , Radiation Dosage , Tomography, Emission-Computed , Tomography, Emission-Computed, Single-PhotonABSTRACT
The MIRD schema is a general approach for medical internal radiation dosimetry. Although the schema has traditionally been used for organ dosimetry, it is also applicable to dosimetry at the suborgan, voxel, multicellular and cellular levels. The MIRD pamphlets that follow in this issue and in coming issues, as well as the recent monograph on cellular dosimetry, demonstrate the flexibility of this approach. Furthermore, these pamphlets provide new tools for radionuclide dosimetry applications, including the dynamic bladder model, S values for small structures within the brain (i.e., suborgan dosimetry), voxel S values for constructing three-dimensional dose distributions and dose-volume histograms and techniques for acquiring quantitative distribution and pharmacokinetic data.
Subject(s)
Nuclear Medicine , Radiotherapy Dosage , Humans , Models, Structural , Models, Theoretical , Radiometry/standardsABSTRACT
The availability of quantitative three-dimensional in vivo data on radionuclide distributions within the body makes it possible to calculate the corresponding nonuniform distribution of radiation absorbed dose in body organs and tissues. This pamphlet emphasizes the utility of the MIRD schema for such calculations through the use of radionuclide S values defined at the voxel level. The use of both dose point-kernels and Monte Carlo simulation methods is also discussed. PET and SPECT imaging can provide quantitative activity data in voxels of several millimeters on edge. For smaller voxel sizes, accurate data cannot be obtained using present imaging technology. For submillimeter dimensions, autoradiographic methods may be used when tissues are obtained through biopsy or autopsy. Sample S value tabulations for five radionuclides within cubical voxels of 3 mm and 6 mm on edge are given in the appendices to this pamphlet. These S values may be used to construct three-dimensional dose profiles for nonuniform distributions of radioactivity encountered in therapeutic and diagnostic nuclear medicine. Data are also tabulated for 131I in 0.1-mm voxels for use in autoradiography. Two examples illustrating the use of voxel S values are given, followed by a discussion of the use of three-dimensional dose distributions in understanding and predicting biologic response.