Corrigendum: Developments in 177Lu-based radiopharmaceutical therapy and dosimetry.

[This corrects the article DOI: 10.3389/fchem.2023.1218670.].

Corrigendum: A single-institution experience with 177Lu RPT workflow improvements and qualifying the SPECT/CT imaging for dosimetry.

[This corrects the article DOI: 10.3389/fonc.2024.1331266.].

A single-institution experience with 177Lu RPT workflow improvements and qualifying the SPECT/CT imaging for dosimetry.

Background and purpose: Implementing any radiopharmaceutical therapy (RPT) program requires a comprehensive review of system readiness, appropriate workflows, and training to ensure safe and efficient treatment delivery. A quantitative assessment of the dose delivered to targets and organs at risk (OAR) using RPT is possible by correlating the absorbed doses with the delivered radioactivity. Integrating dosimetry into an established RPT program demands a thorough analysis of the necessary components and system fine-tuning. This study aims to report an optimized workflow for molecular radiation therapy using 177Lu with a primary focus on integrating patient-specific dosimetry into an established radiopharmaceutical program in a radiation oncology setting. Materials and methods: We comprehensively reviewed using the Plan-Do-Check-Act (PDCA) cycle, including efficacy and accuracy of delivery and all aspects of radiation safety of the RPT program. The GE Discovery SPECT/CT 670DR™ system was calibrated per MIM protocol for dose calculation on MIM SurePlan™ MRT software. Jaszcak Phantom with 15-20 mCi of 177Lu DOTATATE with 2.5 µM EDTA solution was used, with the main energy window defined as 208 keV ±10% (187.6 to 229.2 keV); the upper scatter energy window was set to 240 keV ±5% (228 to 252 keV), while the lower scatter energy window was 177.8 keV ±5% (168.9 to 186.7 keV). Volumetric quality control tests and adjustments were performed to ensure the correct alignment of the table, NM, and CT gantry on SPECT/CT. A comprehensive end-to-end (E2E) test was performed to ensure workflow, functionality, and quantitative dose accuracy. Results: Workflow improvements and checklists are presented after systematically analyzing over 400 administrations of 177Lu-based RPT. Injected activity to each sphere in the NEMA Phantom scan was quantified, and the MIM Sureplan MRT reconstruction images calculated activities within ±12% of the injected activity. Image alignment tests on the SPECT/CT showed a discrepancy of more than the maximum tolerance of 2.2 mm on any individual axis. As a result of servicing the machine and updating the VQC and COR corrections, the hybrid imaging system was adjusted to achieve an accuracy of <1 mm in all directions. Conclusion: Workflows and checklists, after analysis of system readiness and adequate training for staff and patients, are presented. Hardware and software components for patient-specific dosimetry are presented with a focus on hybrid image registration and correcting any errors that affect dosimetric quantification calculation. Moreover, this manuscript briefly overviews the necessary quality assurance requirements for converting diagnostic images into dosimetry measurement tools and integrating dosimetry for RPT based on 177Lu.

Developments in 177Lu-based radiopharmaceutical therapy and dosimetry.

177Lu is a radioisotope that has become increasingly popular as a therapeutic agent for treating various conditions, including neuroendocrine tumors and metastatic prostate cancer. 177Lu-tagged radioligands are molecules precisely designed to target and bind to specific receptors or proteins characteristic of targeted cancer. This review paper will present an overview of the available 177Lu-labelled radioligands currently used to treat patients. Based on recurring, active, and completed clinical trials and other available literature, we evaluate current status, interests, and developments in assessing patient-specific dosimetry, which will define the future of this particular treatment modality. In addition, we will discuss the challenges and opportunities of the existing dosimetry standards to measure and calculate the radiation dose delivered to patients, which is essential for ensuring treatments' safety and efficacy. Finally, this article intends to provide an overview of the current state of 177Lu- tagged radioligand therapy and highlight the areas where further research can improve patient treatment outcomes.

Quantum chemical, spectroscopic and molecular docking investigations of potential pulmonary fibrosis drug methyl 2-chloro 4-iodonicotinate.

In this work, the methyl 2-chloro 4-iodonicotinate (MCIN) was investigated to study the structural, spectroscopic and electronic properties using density functional theory (DFT) quantum chemical calculations. The most stable structure of MCIN was optimized by DFT/B3LYP method with a LanLD2Z basis set. The optimized parameters and vibrational wavenumbers were determined. The vibrational task of the molecule was done by potential energy distribution calculations. The 13 C NMR spectrum of the MCIN molecule was simulated by the Gauge-Invariant-Atomic Orbital method using a dimethyl sulfoxide solution and the isotropic chemical shift values of the molecule were calculated and observed. Ultraviolet-visible spectra were simulated and observed. The pharmaceutical activity was predicted using frontier molecular orbital and natural bond orbital analysis. The reactive sites of the MCIN molecule were determined using Mulliken atomic charge distribution, molecular electrostatic potential surface and the local reactivity analysis. The molecular docking analysis confirms that the title molecule can be used in drug design for the treatment of pulmonary fibrosis.

Feasibility study of utilizing XRV-124 scintillation detector for quality assurance of spot profile in pencil beam scanning proton therapy.

PURPOSE: The purpose of the current study is to (i) investigate the feasibility of utilizing the XRV-124 - a cone-shaped scintillation detector - to measure the spot size and spot position in pencil beam scanning proton therapy, and (ii) compare the spot sizes acquired by the XRV-124 with that of the widely used Lynx detector. METHODS: Spot position was tested by delivering a map of 30 spots at different locations to the XRV-124. Spot position test included energies 70-210 MeV. Spot size measurements were performed at the isocenter using the XRV-124 and Lynx detectors for a total of 32 energies (70-225 MeV at an increment of 5 MeV) at four cardinal gantry angles. RESULTS: The position (X, Y, and Z) of the radiation isocenter was within ±0.3 mm. For spots placed on the horizontal (X) and longitudinal (Y) axes of the spot map, both the X and Y locations of the spots were within ±0.5 mm. The spots placed diagonally in the map showed a higher deviation (±0.9 mm). In evaluating spot sizes acquired using the XRV-124 vs. Lynx, the results from the XRV were found to be slightly higher but within 0.2 mm for energies ≥130 MeV and within 0.4 mm for energies <130 MeV. CONCLUSIONS: It is feasible to utilize the XRV-124 to perform the quality assurance of position and size of a pencil proton beam around the radiation isocenter but within the usable XRV-124 cone area.

Radiobiological and dosimetric impact of RayStation pencil beam and Monte Carlo algorithms on intensity-modulated proton therapy breast cancer plans.

PURPOSE: RayStation treatment planning system employs pencil beam (PB) and Monte Carlo (MC) algorithms for proton dose calculations. The purpose of this study is to evaluate the radiobiological and dosimetric impact of RayStation PB and MC algorithms on the intensity-modulated proton therapy (IMPT) breast plans. METHODS: The current study included ten breast cancer patients, and each patient was treated with 1-2 proton beams to the whole breast/chestwall (CW) and regional lymph nodes in 28 fractions for a total dose of 50.4 Gy relative biological effectiveness (RBE). A total clinical target volume (CTV_Total) was generated by combining individual CTVs: AxI, AxII, AxIII, CW, IMN, and SCVN. All beams in the study were treated with a range shifter (7.5 cm water equivalent thickness). For each patient, three sets of plans were generated: (a) PB optimization followed by PB dose calculation (PB-PB), (b) PB optimization followed by MC dose calculation (PB-MC), and (c) MC optimization followed by MC dose calculation (MC-MC). For a given patient, each plan was robustly optimized on the CTVs with same parameters and objectives. Treatment plans were evaluated using dosimetric and radiobiological indices (equivalent uniform dose (EUD), tumor control probability (TCP), and normal tissue complication probability (NTCP)). RESULTS: The results are averaged over ten breast cancer patients. In comparison to PB-PB plans, PB-MC plans showed a reduction in CTV target dose by 5.3% for D99% and 4.1% for D95% , as well as a reduction in TCP by 1.5-2.1%. Similarly, PB overestimated the EUD of target volumes by 1.8─3.2 Gy(RBE). In contrast, MC-MC plans achieved similar dosimetric and radiobiological (EUD and TCP) results as the ones in PB-PB plans. A selection of one dose calculation algorithm over another did not produce any noticeable differences in the NTCP of the heart, lung, and skin. CONCLUSION: If MC is more accurate than PB as reported in the literature, dosimetric and radiobiological results from the current study suggest that PB overestimates the target dose, EUD, and TCP for IMPT breast cancer treatment. The overestimation of dosimetric and radiobiological results of the target volume by PB needs to be further interpreted in terms of clinical outcome.

Measurements of in-air spot size of pencil proton beam for various air gaps in conjunction with a range shifter on a ProteusPLUS PBS dedicated machine and comparison to the proton dose calculation algorithms.

The purpose of this study is to (i) investigate the impact of various air gaps in conjunction with a range shifter of 7.5 cm water-equivalent-thickness (WET) on in-air spot size of a pencil proton beam at the isocenter and off-axis points, and (ii) compare the treatment planning system (TPS) calculated spot sizes against the measured spot sizes. A scintillation detector has been utilized to measure the in-air spot sizes at the isocenter. The air gap was varied from 0 to 35 cm at an increment of 5 cm. For each air gap, a single spot pencil proton beam of various energies (110-225 MeV) was delivered to the scintillation detector. By mimicking the experimental setup in RayStation TPS, proton dose calculations were performed using pencil beam (RS-PB) and Monte Carlo (RS-MC) dose calculation algorithms. The calculated spot sizes (RS-PB and RS-MC) were then compared against the measured spot sizes. For a comparative purpose, the spot sizes of each measured energy for different air gaps of (5-35 cm) were compared against that of 0 cm air gap. The results of the 5 cm air gap showed an increase in spot size by ≤ 0.6 mm for all energies. For the largest air gap (35 cm) in the current study, the spot size increased by 3.0 mm for the highest energy (225 MeV) and by 9.2 mm for the lowest energy (110 MeV). For the 0 cm air gap, the agreement between the TPS-calculated (RS-PB and RS-MC) and measured spot sizes were within ± 0.1 mm. For the 35 cm air gap, the RS-PB overpredicted spot sizes by 0.3-0.8 mm, whereas the RS-MC computed spot sizes were within ± 0.3 mm of measured spot sizes. In conclusion, spot size increment is dependent on the energy and air gap. The increase in spot size was more pronounced at lower energies ( < 150 MeV) for all air gaps. The comparison between the TPS calculated and measured spot sizes showed that the RS-MC is more accurate (within ± 0.3 mm), whereas the RS-PB overpredicted (up to 0.8 mm) the spot sizes when a range shifter (7.5 cm WET) and large air gaps are encountered in the proton beam path.

Development and long-term stability of a comprehensive daily QA program for a modern pencil beam scanning (PBS) proton therapy delivery system.

PURPOSE: The main purpose of this study is to demonstrate the clinical implementation of a comprehensive pencil beam scanning (PBS) daily quality assurance (QA) program involving a number of novel QA devices including the Sphinx/Lynx/parallel-plate (PPC05) ion chamber and HexaCheck/multiple imaging modality isocentricity (MIMI) imaging phantoms. Additionally, the study highlights the importance of testing the connectivity among oncology information system (OIS), beam delivery/imaging systems, and patient position system at a proton center with multi-vendor equipment and software. METHODS: For dosimetry, a daily QA plan with spot map of four different energies (106, 145, 172, and 221 MeV) is delivered on the delivery system through the OIS. The delivery assesses the dose output, field homogeneity, beam coincidence, beam energy, width, distal-fall-off (DFO), and spot characteristics - for example, position, size, and skewness. As a part of mechanical and imaging QA, a treatment plan with the MIMI phantom serving as the patient is transferred from OIS to imaging system. The HexaCheck/MIMI phantoms are used to assess daily laser accuracy, imaging isocenter accuracy, image registration accuracy, and six-dimensional (6D) positional correction accuracy for the kV imaging system and robotic couch. RESULTS: The daily QA results presented herein are based on 202 daily sets of measurements over a period of 10 months. Total time to perform daily QA tasks at our center is under 30 min. The relative difference (Δrel ) of daily measurements with respect to baseline was within ± 1% for field homogeneity, ±0.5 mm for range, width and DFO, ±1 mm for spots positions, ±10% for in-air spot sigma, ±0.5 spot skewness, and ±1 mm for beam coincidence (except 1 case: Δrel  = 1.3 mm). The average Δrel in dose output was -0.2% (range: -1.1% to 1.5%). For 6D IGRT QA, the average absolute difference (Δabs ) was ≤0.6 ± 0.4 mm for translational and ≤0.5° for rotational shifts. CONCLUSION: The use of novel QA devices such as the Sphinx in conjunction with the Lynx, PPC05 ion chamber, HexaCheck/MIMI phantoms, and myQA software was shown to provide a comprehensive and efficient method for performing daily QA of a number of system parameters for a modern proton PBS-dedicated treatment delivery unit.

Accuracy in automatic image registration between MV cone beam computed tomography and planning kV computed tomography in image guided radiotherapy.

AIM: To verify the accuracy of automatic image registration (IR) between the planning kilo voltage computed tomography (kV CT) and megavoltage cone beam computed tomography (MV CBCT) datasets using phantom and patient images. BACKGROUND: The automatic IR between MV CBCT and planning kV CT is a fast solution for performing online image guided radiotherapy (IGRT). The IR accuracy has to be verified periodically as it directly affects patient setup accuracy. MATERIALS AND METHODS: The automatic IR accuracy was evaluated using image quality phantom acquired with different kV CT slice thickness, different MV CBCT acquisition MUs and reconstruction slice size and thickness. The IR accuracy was also evaluated on patient images on different anatomical sites such as brain, head & neck, thorax and pelvis. The uncertainty in the automatic registration was assessed by introducing known offset to kV CT dataset and compared with the registration results. RESULTS: The result with the phantom images was within 2 mm in all three translational directions. The accuracy in automatic IR using patient images was within 2 mm in most of the cases. 3 mm planning kV CT slice thickness was sufficient to perform automatic IR successfully within 2 mm accuracy. The MV CBCT reconstruction parameters such as slice thickness and slice size had no effect on the registration accuracy. CONCLUSION: This study shows that the automatic IR is accurate within 2 mm and provides confidence in performing them between planning kV CT and MV CBCT image datasets for online image guided radiotherapy.

Current scenario of biomedical aspect of metal-based nanoparticles on gel dosimetry.

In past decades, the possibility of using high atomic number nanoparticle has gained interest in gel dosimetry to enhance the dose deposited in the tumor while using low radiation as well as for better imaging purposes. Sparing of healthy tissues and targeting the tumor part have become much more captivating with the help of these systems. The gel dosimetry is a the three-dimensional dosimeter for extracting the dose, which can be used along with the nanoparticles like gold, platinum, and silver, for better therapeutic efficiency for modern radiotherapy techniques. These nanoparticles of different size prepared either by chemical route or green synthesis and incorporated into the gel system respond in a different manner. Having wide applications in therapeutic field, this study reviews the use of gel dosimeters in the therapeutic procedures and also with the aid of nanoparticles so as to achieve dose enhancement. The biological activity of the various nanoparticles has been discussed.

Assessment and evaluation of MV image guidance system performance in radiotherapy.

BACKGROUND AND AIM: The clinical use of imaging system in image guided radiotherapy (IGRT) necessitates performing periodic quality assurance of the system to be confident in applying corrections for patient set-up errors. We aim to develop and implement a quality assurance (QA) programme for megavoltage (MV) based image guidance system and assess its long term performance for a period of 3 years. MATERIALS AND METHODS: Periodic QA tests were performed for the MV planar and cone beam computed tomography (CBCT) imaging system to assess the system safety, mechanical and geometrical accuracy, image quality and dose. The tests were performed using the equipment supplied by the manufacturer along with the image guidance system and using simple methods developed in-house. The test results were compared with expected or baseline values established during commissioning. RESULTS: The safety system was found to be functional. The results of mechanical and geometrical tests were in good agreement with the expected results. The system mechanical positioning was stable and reproducible within ±2 mm accuracy. The image quality and the imaging dose of the planar and CBCT imaging were found to agree with the baseline values and the manufacturer specifications. DISCUSSION: Throughout the three-year period, all the QA tests were within the specification. The mechanical and geometrical tests are most crucial as they directly affect the patient positioning accuracy. CONCLUSION: We conclude that the MV image guidance system is efficient to perform IGRT and insist to perform periodic QA tests and calibration for the system.

Quantum mechanical and spectroscopic (FT-IR, FT-Raman, 13C, 1H and UV) investigations of antiepileptic drug Ethosuximide.

The Fourier Transform Infrared (FT-IR) and Fourier Transform Raman (FT-Raman) spectra of antiepileptic drug Ethosuximide (ETX) have been recorded and analyzed. In addition, the IR spectra in CCl(4) at various concentrations of ETX are also recorded. The equilibrium geometry, bonding features and harmonic vibrational frequencies have been investigated with the help of Density Functional Theory (DFT) method. The (1)H and (13)C nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by the Gauge Including Atomic Orbital (GIAO) method. Stability of the molecule arising from hyperconjugative interactions and charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The results show that charge in electron density (ED) in the σ* and π* antibonding orbitals and second order delocalization energies E(2) confirms the occurrence of intramolecular charge transfer (ICT) within the molecule. UV-vis spectrum of the compound was recorded and the electronic properties, such as HOMO and LUMO energies, were performed by Time-Dependent Density Functional Theory (TD-DFT) approach. Finally the calculation results were applied to simulate infrared and Raman spectra of the title compound which showed good agreement with observed spectra.