Original Knee Fixation Device as a Useful Fixation Method during Prostate Intensity-Modulated Radiation Therapy.

Purpose: The purpose of he study was to reduce setup errors during intensity-modulated radiation therapy (IMRT) with an original knee fixation device (KFD) and evaluate the clinical target volume (CTV) coverage. Methods: Participants were classified into two groups: knee flexion (KF) group (n = 16), wherein participants' knees were fixed in a flexed position using the proposed KFD during planning computed tomography, and knee extension group (KE; n = 15), wherein no KFD was used. We investigated the residual rotational errors and inter-fractional setup errors with or without KFD. Furthermore, inter-fractional margins were calculated using logistic regression analysis, and CTV coverage was evaluated. Results: The residual rotational errors in the yaw and roll directions (P < 0.02) and the inter-fractional error in the anterior-posterior (A-P) direction (P < 0.02) improved significantly in the KF group compared with the KE group. Repeatability was improved for the pitch direction. The inter-fractional margins were 6.68 mm and 4.87 mm in the A-P and superior-inferior (S-I) directions, respectively, in the KF group, representing reductions (mm) of 20.8% and 12.6% compared with the KE group, respectively. The odds ratios for CTV coverage in the KF group compared to the KE group were 2.76 (P < 0.001) and 1.74 (P < 0.05) in the A-P and S-I directions, respectively. Conclusions: The IMRT fixation method using an original KFD improved the residual rotational error in the three directions and the inter-fractional error in the A-P direction, reduced the interfractional margins in the A-P, and S-I directions and improved CTV coverage. Our original KFD may be a useful fixation method during prostate IMRT.

Evaluation of Absorbed Dose for CBCT in Image-guided Radiation Therapy: Comparison of Each Devices and Facilities.

Recently, intensity-modulated radiation therapy (IMRT) is used worldwide, highly accurate verification of the location using image-guided radiation therapy (IGRT) has become critical. However, the use of cone-beam computed tomography (CBCT) to ascertain the location each time raises concerns about its influence on radiotherapy dosage and increased radiation exposure. The purpose of this study was to measure the absorbed dose using nine kilovoltage (kV) devices and two megavoltage (MV) devices (total 11 devices) at eight facilities, compare the absorbed dose among the devices, and assess the characteristics of the respective devices to ensure optimal clinical operation. For the measurement of the absorbed dose, a farmer-type ionization chamber dosimeter, calibrated using a 60Co and an IMRT dose verification phantom manufactured from water-equivalent material RW3, was used to measure the absorbed dose at nine points in the phantom for two regions, the pelvic and cephalic region. The average absorbed dose of the pelvic region was 3.09±0.21 cGy in kV-CBCT (OBI), 1.16±0.16 cGy in kV-CBCT (XVI), 5.64±1.48 cGy in MV-CBCT (4 MV), and 6.33±1.54 cGy in MV-CBCT (6 MV). The average absorbed dose of the cephalic region was 0.38±0.03 cGy in kV-CBCT (OBI), 0.23±0.06 cGy in kV-CBCT (XVI), 4.02±0.72 cGy in MV-CBCT (4 MV), and 4.46±0.77 cGy in MV-CBCT (6 MV). There was a difference in the absorbed dose at the measured points as well as in the dose distribution in the phantom cross section. No major difference was observed in the absorbed dose among identical devices, but a difference was identified among the devices installed at multiple facilities. Therefore, the angle of rotation should be paid attention to when CBCT is taken, and the image-taking conditions should be determined. In addition, it is important to handle the devices only after ascertaining the absorbed dose of each device.

[Impact of exposure dose reduction of radiation treatment planning CT using low tube voltage technique].

PURPOSE: The aim of this study was to reduce the exposed dose of radiotherapy treatment planning computed tomography (CT) by using low tube voltage technique. MATERIALS AND METHODS: We used tube voltages of 80 kV, 100 kV, and 120 kV, respectively. First, we evaluated exposure dose with CT dose index (CTDI) for each voltage. Second, we compared image quality indexes such as modulation transfer function (MTF), noise power spectrum (NPS), and contrast to noise ratio (CNR) of phantom images with each voltage. Third, CT to electron density tables were measured in three voltages and monitor unit value was calculated along with clinical cases. Finally, CT surface exposed dose of chest skin was measured by thermoluminescent dosimeter (TLD). RESULTS: In image evaluation MTF and NPS were approximately equal; CNR slightly decreased, 2.0% for 100 kV. We performed check radiation dose accuracy for each tube voltage with each model phantom. As a result, the difference of MU value was not accepted. Finally, compared with 120 kV, CTDIvol and TLD value showed markedly decreased radiation dose, 60% for 80 kV and 30% for 100 kV. CONCLUSION: Using a technique with low tube voltages, especially 100 kV, is useful in radiotherapy treatment planning to obtain 20% dose reduction without compromising 120 kV image quality.

Pharmacokinetic alteration of (99m)Tc-MAG3 using serum protein binding displacement method.

INTRODUCTION: When a radiopharmaceutical is simultaneously administered with a medicine that has high affinity for the same plasma protein, the radiopharmaceutical is released at higher concentrations in blood, leading to enhanced transfer into target tissues. This is known as the serum protein binding displacement method. In this study, we investigated the pharmacokinetic alteration of technetium-99m-labeled mercaptoacetylglycylglycylglycine ((99m)Tc-MAG3) using the serum protein binding displacement method. METHODS: Rat and human serum protein binding rates of (99m)Tc-MAG3 were measured by ultrafiltration with or without displacers of human serum albumin (HSA) binding sites I and II (200µM and 400µM loading). Male Wistar rats were injected with (99m)Tc-MAG3 (740kBq/0.3mL saline) via the tail vein, and biodistribution was assessed at 2, 5, 10 and 15min. Dynamic whole-body images were obtained for (99m)Tc-MAG3 (11.1MBq/0.3mL saline)-injected rats, with or without HSA displacers. RESULTS: (99m)Tc-MAG3 strongly bound to HSA (87.37%±2.13%). Using HSA site I displacers, the free fraction of (99m)Tc-MAG3 increased significantly (1.20 to 1.47 times) when compared with controls. For biodistribution and imaging, rapid blood clearance was observed with bucolome (BCL) loading, which is an HSA site I displacer. With BCL loading, peak times for rat renograms were respectively shifted from 240s to 110s, and from 170s to 120s. CONCLUSIONS: We found that (99m)Tc-MAG3 bound to the HSA binding site I. It was confirmed that pharmacokinetic distribution of (99m)Tc-MAG3 is altered by presence of BCL, which leads to increases in the free fraction of (99m)Tc-MAG3, and BCL produced rapid blood clearance and fast peak times on rat renograms. The serum protein binding displacement method using (99m)Tc-MAG3 and BCL, a safe displacer for humans, may be applicable to clinical study and lead to better diagnostic images with shorter waiting times and lower radiation doses for patients.

The agreement of left ventricular function parameters between (99m)Tc-tetrofosmin gated myocardial SPECT and gated myocardial MRI.

OBJECTIVE: The aim is to compare and evaluate the agreement of quantification of left ventricular functional parameters obtained by two different methods, (99m)Tc-tetrofosmin gated myocardial perfusion SPECT (MPS) and cardiac magnetic resonance imaging (CMR). METHODS: Ten healthy male volunteers participated. Gated MPS data were acquired using 32 frames, which were also combined into 16- and 8-frame data set for the investigation. Gated CMR data were acquired using 8, 16 and 32-frame for the different sets. All examinations were conducted in resting and at exercise conditions. Quantitative measurements of end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular ejection fraction (LVEF), peak ejection rate (PER), peak filling rate (PFR) and time to peak filling (TTPF) were done for each study, respectively. Finally, we evaluated the concordance of parameters between gated MPS and gated CMR by % difference and Bland-Altman plot analysis. RESULTS: LVEF showed favorable concordance in both rest and exercise conditions (% differences were around 10%). PER, PFR and TTPF also showed good concordances in rest conditions, under 32-frame gated collections particularly (% differences were around 10%). In exercise conditions, although the concordances were relatively good, certain variances were noted (% differences were around 20-25%). Regarding left ventricular volumes, the concordance were worse in both conditions (% differences were around 30-40%). CONCLUSIONS: In quantifying of left ventricular function parameter, gated CMR provides similar quantitative values comparing with gated MPS except for ventricular volumes in rest conditions. In contrast, there were certain variations except for LVEF in exercised examinations. When we follow patients by the same cardiac parameters with CMR and MPS, using parameters across the two modalities proved to be possible under rest condition. However, it is limited at exercise condition.

Competitive displacement of serum protein binding of radiopharmaceuticals with amino acid infusion investigated with N-isopropyl-p-123I-iodoamphetamine.

UNLABELLED: When a therapeutic drug is competitively displaced at the binding sites of serum proteins, the free fraction of the drug will be increased, with an increase in the manifestation of pharmacologic properties. In the case of molecular imaging probes, total clearance and tissue distribution are increased in such circumstances. The aim of this study was to observe the increase in cerebral accumulation of N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) using the protein-binding displacement method with amino acid infusion. METHODS: (123)I-IMP binding to human serum was investigated and identified. In addition, protein-binding sites and the specific binding sites of human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP) were examined by ultrafiltration. Then, serum-binding sites and the displacement effects of amino acid infusion, including Proteamin 12X Injection and Kidomin, were confirmed in vitro. Subsequently, displacement of (123)I-IMP serum protein binding with Proteamin amino acid infusion was tested in monkeys. A scintigraphic study of (123)I-IMP in monkeys loaded with or without Proteamin was performed, and time-activity-curves of (123)I-IMP brain accumulation in monkeys were evaluated. RESULTS: (123)I-IMP was bound to HSA site II and AGP to nearly equal extents. Compared with control conditions, loading with Proteamin and Kidomin markedly increased free fractions of binding site markers for HSA site II ((14)C-diazepam: 0.95% +/- 0.04% for control, 1.40% +/- 0.06% for Proteamin, 1.62% +/- 0.05% for Kidomin) and AGP ((3)H-propranolol: 10.60% +/- 0.32% for control, 13.18% +/- 0.14% for Proteamin, 13.82% +/- 0.72% for Kidomin). Amino acid infusions were thus suitable for use as displacers for binding site II and AGP. With use of Proteamin amino acid infusion to displace protein binding, the free fraction of (125)I-IMP (14.95% +/- 0.74%) was significantly increased in serum (19.24% +/- 0.87%). In a (123)I-IMP scintigraphic study of monkeys, average cerebral uptake in 2 monkeys increased by 1.34-fold with Proteamin. Our findings suggested that Proteamin treatment increased the free fraction of (123)I-IMP, yielding rapid and pronounced cerebral accumulation in vivo. CONCLUSION: Amino acid infusion can improve brain accumulation by competitive displacement of serum protein binding in vivo. Further similar studies are needed with other radiopharmaceuticals.

Serum protein binding displacement: theoretical analysis using a hypothetical radiopharmaceutical and experimental analysis with 123I-N-isopropyl-p-iodoamphetamine.

INTRODUCTION: The binding of radiopharmaceutical to serum proteins is thought to be an important factor that restricts its excretion and accumulation in tissue. We calculated the effect of inhibitors of serum protein binding using a hypothetical radiopharmaceutical. In vitro experiments and protein binding inhibitor-loaded monkey scintigraphy were then conducted using (123)I-N-isopropyl-p-iodoamphetamine (IMP) as the radiopharmaceutical. METHODS: Free fraction ratios of radiopharmaceutical were calculated with one radiopharmaceutical, two serum proteins and two specific inhibitors in the steady state at various serum protein concentrations. In vitro protein binding inhibition studies using human, rat and monkey sera were performed with site-selective displacers of specific binding sites: 400 microM 6-methoxy-2-naphthylacetic acid (6MNA; a major nabumeton metabolite) as a serum albumin Site II inhibitor and 400 microM erythromycin (ETC) as an alpha(1)-acid glycoprotein (AGP) site inhibitor. Scintigraphy with or without 6MNA loading of monkeys was performed. RESULTS: The theoretical findings roughly corresponded to the experimental results. Approximately 75% of IMP bound to serum albumin Site II and AGP in the species examined. The free fraction of IMP (25.0+/-0.6% for human, 22.8+/-0.4% for monkey, 23.7+/-0.3% for rat) increased with loading of specific protein binding inhibitors (6MNA: 28.0+/-0.3% for human, 24.5+/-0.7% for monkey, 24.3+/-0.2% for rat; ETC: 26.3+/-0.4% for human, 29.5+/-1.1% for monkey, 26.0+/-0.7% for rat) and was serum protein concentration dependant based on the results of calculations. Simultaneous administration of 6MNA and ETC produced a higher free fraction ratio of IMP (31.9+/-1.0% for human, 34.6+/-0.4% for monkey, 27.0+/-0.3% for rat) than summation of the single administrations of 6MNA and ETC (domino effect) in human, rat and monkey sera. Rapid cerebral accumulation was observed with 6MNA loading in monkey scintigraphy. CONCLUSIONS: 6MNA appears to change the pharmacokinetics and brain accumulation of IMP in monkeys. Further studies in human are required.

Inhibitory effects of amino-acid fluids on drug binding to site II of human serum albumin in vitro.

The effects of amino-acid fluids on ligand binding to human serum albumin (HSA) were investigated by fluorescence and ultrafiltration techniques. Warfarin and dansylsarcosine were used as the site marker fluorescence probes for site I and site II of HSA, respectively. Amino-acid fluids specifically decreased the fluorescence intensity induced by dansylsarcosine-HSA binding without any effects on that induced by warfarin-HSA binding. The ultrafiltration technique clarified that the free fraction of the site II drug, diazepam, in human serum was increased in the presence of amino-acid fluids, while no effect was observed in the free fraction of the site I drug, warfarin. The potencies of the effect on binding to site II, observed by fluorescence and ultrafiltration techniques, correlated well with the L-tryptophan contents in amino-acid fluids or with those in L-tryptophan solutions. Based on the comparison between the effects of amino-acid fluids and L-tryptophan solutions, we confirmed that L-tryptophan in amino-acid fluids specifically inhibits drug binding to site II of HSA.

Effects of irradiation on the components of implantable pacemakers.

The purpose of this study was to examine the effects of irradiation on implantable pacemaker components. The pacemaker was divided into three components: lead wire and electrode, battery, and electrical circuit, and each component was irradiated by X-ray and electron beams, respectively. The pacemaker parameters were measured by both telemetry data of the programmer and directly measured data from the output terminal. The following results were obtained. For the lead wire and electrode, there was no effect on the pacemaker function due to irradiation by X-ray and electron beams. In the case of battery irradiation, there was no change in battery voltage or current up to 236Gy X-ray dose. In the electrical circuit, the pacemaker reverted to the regular beating rate (fixed-rate mode) immediately after the start of X-ray irradiation, and it continued in this mode during irradiation. In patients with their own heartbeat rhythm, changing to the fixed-rate mode may cause dangerous conditions such as ventricular fibrillation. When the accumulated irradiation dose is increased, another failure can be seen in the output voltage of the pacemaker. The pacing output voltage dropped rapidly by about 40 % at 30-88Gy. Decreasing the output voltage results in pacing disorders, and heart failure may occur. In the telemetry data of the programmer, no change in output voltage could be detected, highlighting the difference between telemetry data and actual pacing data.