Ju-Un Lee

Novel E. coli β-ketoacyl-acyl carrier protein synthase III inhibitors as targeted antibiotics

Beta-ketoacyl-acyl carrier protein synthase (KAS) III is a condensing enzyme that initiates fatty acid biosynthesis in most bacteria. We determined three pharmacophore maps from receptor-oriented pharmacophore-based in silico screening of the X-ray structure of Escherichia coli KAS III (ecKAS III) and choose 16 compounds as candidate ecKAS III inhibitors. Binding inhibitors were characterized using saturation-transfer difference NMR spectroscopy (STD-NMR), and binding constants were determined with fluorescence quenching experiments. Based on the results, we propose that the antimicrobial compound, 4-cyclohexyliminomethyl-benzene-1,3-diol (YKAs3003), is a potent inhibitor of pathogenic KAS III, displaying minimal inhibitory concentration (MIC) values in the range 128-256 microg/mL against various bacteria.

SU-F-T-545: Dosimetric and Radiobiological Evaluation of Dose Calculation Algorithms On Prostate Stereotactic Body Radiotherapy Using Conventional Flattened and Flattening-Filter-Free Beam

PURPOSE The purpose of this study is to evaluate the dosimetric and radiobiological impact of Acuros XB (AXB) and Anisotropic Analytic Algorithm (AAA) dose calculation algorithms on prostate stereotactic body radiation therapy plans with both conventional flattened (FF) and flattening-filter free (FFF) modes. METHODS For thirteen patients with prostate cancer, SBRT planning was performed using 10-MV photon beam with FF and FFF modes. The total dose prescribed to the PTV was 42.7 Gy in 7 fractions. All plans were initially calculated using AAA algorithm in Eclipse treatment planning system (11.0.34), and then were re-calculated using AXB with the same MUs and MLC files. The four types of plans for different algorithms and beam energies were compared in terms of homogeneity and conformity. To evaluate the radiobiological impact, the tumor control probability (TCP) and normal tissue complication probability (NTCP) calculations were performed. RESULTS For PTV, both calculation algorithms and beam modes lead to comparable homogeneity and conformity. However, the averaged TCP values in AXB plans were always lower than in AAA plans with an average difference of 5.3% and 6.1% for 10-MV FFF and FF beam, respectively. In addition, the averaged NTCP values for organs at risk (OARs) were comparable. CONCLUSION This study showed that prostate SBRT plan were comparable dosimetric results with different dose calculation algorithms as well as delivery beam modes. For biological results, even though NTCP values for both calculation algorithms and beam modes were similar, AXB plans produced slightly lower TCP compared to the AAA plans.

SU-F-T-625: Optimal Treatment Planning Strategy Among Arc Arrangements for Prostate SBRT with VMAT Technique

PURPOSE The purpose of this study is to determine the optimal treatment planning strategy among the different arc arrangements for prostate stereotactic body radiotherapy (SBRT) plans with volumetric modulated arc therapy (VMAT). METHODS Ten patients with prostate cancer were selected. The SBRT-VMAT plans for each patient were generated with single-full (181° to 179°; 1FA), single-partial (240° to 120°; 1PA), double-full (181° to 179° and 179° to 181°; 2FA), and double-partial (240° to 120° and 120° to 240°; 2PA) arc arrangements. The prescription dose was 42.7 Gy in 7 fractions. Dose distribution was calculated using a 10-MV flattening-filter-free beam and the Acuros XB algorithm. Dosimetric parameters of target volume and organs at risk (OARs) were evaluated from cumulative dose-volume histograms on prostate SBRT-VMAT plans between single-arc (1FA and 1PA) and double-arc (2FA and 2PA) arrangements. RESULTS All plans using four arc arrangements were highly conformal with conformity index (CI)<1.05 and conformation number (CN)=0.91, and the doses to target volume were homogeneous (homogeneity index (HI)= 0.09 0.12). Pertaining to the dose to the OARs, there were significant differences in the rectum, left and right femoral head doses while having no difference in the bladder dose. The partial-arc (1PA and 2PA) had relatively high reductions for the mean rectum dose compared to full-arc (1FA and 2FA). The near-to-maximum dose (D2%) and mean dose of the left and right femoral head were always lower on prostate SBRT-VMAT plan using the full-arc, when compared to the partial-arc arrangement. CONCLUSION This study confirmed that prostate SBRT-VMAT using 1PA was feasible fast delivery time and produced equivalent target coverage and better rectum sparing, although the D2% and mean dose of the left and right femoral head increased slightly. Therefore, the results of this study suggest that the use of 1PA is an attractive choice for delivering prostate SBRT-VMAT.

SU-E-T-802: Verification of Implanted Cardiac Pacemaker Doses in Intensity-Modulated Radiation Therapy: Dose Prediction Accuracy and Reduction Effect of a Lead Sheet

Purpose: To verify delivered doses on the implanted cardiac pacemaker, predicted doses with and without dose reduction method were verified using the MOSFET detectors in terms of beam delivery and dose calculation techniques in intensity-modulated radiation therapy (IMRT). Methods: The pacemaker doses for a patient with a tongue cancer were predicted according to the beam delivery methods [step-and-shoot (SS) and sliding window (SW)], intensity levels for dose optimization, and dose calculation algorithms. Dosimetric effects on the pacemaker were calculated three dose engines: pencil-beam convolution (PBC), analytical anisotropic algorithm (AAA), and Acuros-XB. A lead shield of 2 mm thickness was designed for minimizing irradiated doses to the pacemaker. Dose variations affected by the heterogeneous material properties of the pacemaker and effectiveness of the lead shield were predicted by the Acuros-XB. Dose prediction accuracy and the feasibility of the dose reduction strategy were verified based on the measured skin doses right above the pacemaker using mosfet detectors during the radiation treatment. Results: The Acuros-XB showed underestimated skin doses and overestimated doses by the lead-shield effect, even though the lower dose disagreement was observed. It led to improved dose prediction with higher intensity level of dose optimization in IMRT. The dedicated tertiary lead sheet effectively achieved reduction of pacemaker dose up to 60%. Conclusion: The current SS technique could deliver lower scattered doses than recommendation criteria, however, use of the lead sheet contributed to reduce scattered doses.Thin lead plate can be a useful tertiary shielder and it could not acuse malfunction or electrical damage of the implanted pacemaker in IMRT. It is required to estimate more accurate scattered doses of the patient with medical device to design proper dose reduction strategy.

SU‐E‐T‐131: Dosimetric Impact and Evaluation of Different Heterogenity Algorithm in Volumetric Modulated Arc Therapy Plan for Stereotactic Ablative Radiotherapy Lung Treatment with the Flattening Filter Free Beam

PURPOSE The present study aimed to investigate the dosimetric impacts of the anisotropic analytic algorithm (AAA) and the Acuros XB (AXB) plan for lung stereotactic ablative radiation therapy using flattening filter-free (FFF) beam. We retrospectively analyzed 10 patients. METHODS We retrospectively analyzed 10 patients. The dosimetric parameters for the target and organs at risk (OARs) from the treatment plans calculated with these dose calculation algorithms were compared. The technical parameters, such as the computation times and the total monitor units (MUs), were also evaluated. RESULTS A comparison of DVHs from AXB and AAA showed that the AXB plan produced a high maximum PTV dose by average 4.40% with a statistical significance but slightly lower mean PTV dose by average 5.20% compared to the AAA plans. The maximum dose to the lung was slightly higher in the AXB compared to the AAA. For both algorithms, the values of V5, V10 and V20 for ipsilateral lung were higher in the AXB plan more than those of AAA. However, these parameters for contralateral lung were comparable. The differences of maximum dose for the spinal cord and heart were also small. The computation time of AXB was found fast with the relative difference of 13.7% than those of AAA. The average of monitor units (MUs) for all patients was higher in AXB plans than in the AAA plans. These results indicated that the difference between AXB and AAA are large in heterogeneous region with low density. CONCLUSION The AXB provided the advantages such as the accuracy of calculations and the reduction of the computation time in lung stereotactic ablative radiotherapy (SABR) with using FFF beam, especially for VMAT planning. In dose calculation with the media of different density, therefore, the careful attention should be taken regarding the impacts of different heterogeneity correction algorithms. The authors report no conflicts of interest.

Effects of Substitutions of Gln16 and Asp18 with Phe or Tyr in HP(2-20) on its Structure and Antimicrobial Activity

HP (2-20), a 19-residue peptide derived from the N-terminus of Helicobacter pylori Ribosomal Protein L1, has antimicrobial activity but is not cytotoxic to human erythrocytes. Previously, we have synthesized several analogue peptides to investigate the effects of substitutions on the structure and antimicrobial activity. Substitution of and with Trp (Anal 3) caused a dramatic increase in bacterial and fungal lytic activities. In this study, analogue peptides were synthesized to investigate the effects of substitution of Gin and Asp with Phe (Anal 6) or Tyr (Anal 7) in HP (2-20) on its structure and antimicrobial activity. Substitution of Gin and Asp with hydrophobic aromatic residues at position 16 and 18 of HP (2-20) caused increase in antibiotic activity without hemolytic effect. Substitution of Gin and Asp with Trp and Try increased antibiotic activity of HP (220) twice more compared to substitution with Phe. The tertiary structures of Anal 6 and Anal 7 in SDS micelles has been investigated using NMR spectroscopy. The structures revealed that substitutions of the aromatic residues at C-terminus resulted in longer and well defined alpha-helix and improved their antibacterial activities