Probing disorder in 2CzPN using core and valence states.

Molecules which exhibit thermally activated delayed fluorescence (TADF) show great promise for use in efficient, environmentally-friendly OLEDs, and thus the design of new TADF emitters is an active area of research. However, when used in devices, they are typically in the form of disordered thin films, where both the external molecular environment and thermally-induced internal variations in parameters such as the torsion angle can strongly influence their electronic structure. In this work, we use density functional theory and X-ray photoelectron spectroscopy to investigate the impact of disorder on both core and valence states in the TADF emitter 2CzPN (1,2-bis(carbazol-9-yl)-4,5-dicyanobenzene). By simulating gas phase molecules displaying varying levels of disorder, we assess the relative sensitivity of the different states to factors such as varying torsion angle. The theoretical results for both core and valence states show good agreement with experiment, thereby also highlighting the advantages of our approach for interpreting experimental spectra of large aromatic molecules, which are too complex to interpret based solely on experimental data.

Fast Molecular Compression by a Hyperthermal Collision Gives Bond-Selective Mechanochemistry.

Using electrospray ion beam deposition, we collide the complex molecule Reichardt's dye (C_{41}H_{30}NO^{+}) at low, hyperthermal translational energy (2-50 eV) with a Cu(100) surface and image the outcome at single-molecule level by scanning tunneling microscopy. We observe bond-selective reaction induced by the translational kinetic energy. The collision impulse compresses the molecule and bends specific bonds, prompting them to react selectively. This dynamics drives the system to seek thermally inaccessible reactive pathways, since the compression timescale (subpicosecond) is much shorter than the thermalization timescale (nanosecond), thereby yielding reaction products that are unobtainable thermally.

Detecting Proteomic Indicators to Distinguish Diabetic Nephropathy from Hypertensive Nephrosclerosis by Integrating Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging with High-Mass Accuracy Mass Spectrometry.

INTRODUCTION: Diabetic nephropathy (DN) and hypertensive nephrosclerosis (HN) represent the most common causes of chronic kidney disease (CKD) and many patients progress to -end-stage renal disease. Patients are treated primarily through the management of cardiovas-cular risk factors and hypertension; however patients with HN have a more favorable outcome. A noninvasive clinical approach to separate these two entities, especially in hypertensive patients who also have diabetes, would allow for targeted treatment and more appropriate resource allocation to those patients at the highest risk of CKD progression. Meth-ods: In this preliminary study, high-spatial-resolution matrix-assisted laser desorption/ion-ization (MALDI) mass spectrometry imaging (MSI) was integrated with high-mass accuracy MALDI-FTICR-MS and nLC-ESI-MS/MS analysis in order to detect tissue proteins within kidney biopsies to discriminate cases of DN (n = 9) from cases of HN (n = 9). RESULTS: Differences in the tryptic peptide profiles of the 2 groups could clearly be detected, with these becoming even more evident in the more severe histological classes, even if this was not evident with routine histology. In particular, 4 putative proteins were detected and had a higher signal intensity within regions of DN tissue with extensive sclerosis or fibrosis. Among these, 2 proteins (PGRMC1 and CO3) had a signal intensity that increased at the latter stages of the disease and may be associated with progression. DISCUSSION/CONCLUSION: This preliminary study represents a valuable starting point for a future study employing a larger cohort of patients to develop sensitive and specific protein biomarkers that could reliably differentiate between diabetic and hypertensive causes of CKD to allow for improved diagnosis, fewer biopsy procedures, and refined treatment approaches for clinicians.

Flexibilities of wavelets as a computational basis set for large-scale electronic structure calculations.

The BigDFT project was started in 2005 with the aim of testing the advantages of using a Daubechies wavelet basis set for Kohn-Sham (KS) density functional theory (DFT) with pseudopotentials. This project led to the creation of the BigDFT code, which employs a computational approach with optimal features of flexibility, performance, and precision of the results. In particular, the employed formalism has enabled the implementation of an algorithm able to tackle DFT calculations of large systems, up to many thousands of atoms, with a computational effort that scales linearly with the number of atoms. In this work, we recall some of the features that have been made possible by the peculiar properties of Daubechies wavelets. In particular, we focus our attention on the usage of DFT for large-scale systems. We show how the localized description of the KS problem, emerging from the features of the basis set, is helpful in providing a simplified description of large-scale electronic structure calculations. We provide some examples on how such a simplified description can be employed, and we consider, among the case-studies, the SARS-CoV-2 main protease.

The management of haemoglobin interference for the MALDI-MSI proteomics analysis of thyroid fine needle aspiration biopsies.

MALDI-MSI represents an ideal tool to explore the spatial distribution of proteins directly in situ, integrating molecular and cytomorphological information, enabling the discovery of potential diagnostic markers in thyroid cytopathology. However, red cells present in the fine needle aspiration biopsy (FNAB) specimens caused ion suppression of other proteins during the MALDI-MSI analysis due to large amount of haemoglobin. Aim of this study was to set up a sample preparation workflow able to manage this haemoglobin interference. Three protocols were compared using ex vivo cytological samples collected from fresh thyroid nodules of 9 patients who underwent thyroidectomy: (A) conventional air-dried smears, (B) cytological smears immediately fixed in ethanol, and (C) ThinPrep liquid-based preparation. Protocols C and A were also evaluated using real FNABs. Results show that protocol C markedly decreased the amount of haemoglobin, with respect to protocols A and B. Protein profiles obtained with protocols A and B were characterised by high inter-patient variability, probably related to the abundance of the haemoglobin, whereas similar spectra were observed for protocol C, where haemoglobin contents were lower. Our findings suggest protocol C as the sample preparation method for MALDI-MSI analysis. Graphical abstract.

Effects of Hematuria on the Proteomic Profile of Urinary Extracellular Vesicles: Technical Challenges.

Hematuria is a common sign of many renal and urologic pathologic conditions and it may affect the proteomic analysis of urinary extracellular vesicles (UEv), nanovesicles released from all cells in contact with the urinary space. This condition hinders UEv based proteomic studies aiming to discover biomarkers. Therefore, we studied the effects of hematuria on the proteome of UEv and introduced a possible solution to reduce its misleading impact. We mimicked hematuria by adding increasing amount of blood to nonaffected urine and investigated its effects on UEv isolation, purity, and proteomic composition. We proposed a trypsin treatment able to reduce the impact of hematuria on UEv. The effects of the treatment were investigated by evaluating the UEv proteomic profile, the enrichment of known UEv markers, and by assessing differential protein content by MS-based label-free quantification. Results showed that as the blood contamination increased, it affected both the proteome profile and the yield of UEv isolated from urine. Our treatment with trypsin was able to counteract completely these effects for low/medium levels of hematuria, which are most commonly encountered. This promising finding could lead to the reliable use of hematuria samples for UEv proteomic investigation.

The putative role of MALDI-MSI in the study of Membranous Nephropathy.

Membranous Nephropathy (MN) is an immunocomplex mediated renal disease that represents one of the most frequent glomerulopathies worldwide. This glomerular disease can manifest as primary (idiopathic) or secondary and this distinction is crucial when choosing the most appropriate course of treatment. In secondary cases, the best strategy involves treating the underlying disease, whereas in primary forms, the identification of confirmatory markers of the idiopathic etiology underlining the process is requested by clinicians. Among those currently reported, the positivity to circulating antigens (PLA2R, IgG4 and THSD7A) was demonstrated in approximately 75% of iMN patients, while approximately 1 in 4 patients with iMN still lack a putative diagnostic marker. Ultimately, the discovery of biomarkers to help further stratify these two different forms of glomerulopathy seems mandatory. Here, MALDI-MSI was applied to FFPE renal biopsies from histologically diagnosed primary and secondary MN patients (n=20) in order to detect alterations in their tissue proteome. MALDI-MSI was able to generate molecular signatures of primary and secondary MN, with one particular signal (m/z 1459), identified as Serine/threonine-protein kinase MRCK gamma, being over-expressed in the glomeruli of primary MN patients with respect to secondary MN. Furthermore, a number of signals that could differentiate the different forms of iMN that were positive to PLA2R or IgG4 were detected, as well as a further set of signals (m/z 1094, 1116, 1381 and 1459) that could distinguish these patients from those who were negative to both. These signals could potentially represent future targets for the further stratification of iMN patients. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.

Proteomic profiles of thyroid tumors by mass spectrometry-imaging on tissue microarrays.

The current study proposes the successful use of a mass spectrometry-imaging technology that explores the composition of biomolecules and their spatial distribution directly on-tissue to differentially classify benign and malignant cases, as well as different histotypes. To identify new specific markers, we investigated with this technology a wide histological Tissue Microarray (TMA)-based thyroid lesion series. Results showed specific protein signatures for malignant and benign specimens and allowed to build clusters comprising several proteins with discriminant capabilities. Among them, FINC, ACTB1, LMNA, HSP7C and KAD1 were identified by LC-ESI-MS/MS and found up-expressed in malignant lesions. These findings represent the opening of further investigations for their translation into clinical practice, e.g. for setting up new immunohistochemical stainings, and for a better understanding of thyroid lesions. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.

Matrix-Assisted Laser Desorption/Ionisation Mass Spectrometry Imaging in the Study of Gastric Cancer: A Mini Review.

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide and the disease outcome commonly depends upon the tumour stage at the time of diagnosis. However, this cancer can often be asymptomatic during the early stages and remain undetected until the later stages of tumour development, having a significant impact on patient prognosis. However, our comprehension of the mechanisms underlying the development of gastric malignancies is still lacking. For these reasons, the search for new diagnostic and prognostic markers for gastric cancer is an ongoing pursuit. Modern mass spectrometry imaging (MSI) techniques, in particular matrix-assisted laser desorption/ionisation (MALDI), have emerged as a plausible tool in clinical pathology as a whole. More specifically, MALDI-MSI is being increasingly employed in the study of gastric cancer and has already elucidated some important disease checkpoints that may help us to better understand the molecular mechanisms underpinning this aggressive cancer. Here we report the state of the art of MALDI-MSI approaches, ranging from sample preparation to statistical analysis, and provide a complete review of the key findings that have been reported in the literature thus far.

Extracting histones for the specific purpose of label-free MS.

Extracting histones from cells is the first step in studies that aim to characterize histones and their post-translational modifications (hPTMs) with MS. In the last decade, label-free quantification is more frequently being used for MS-based histone characterization. However, many histone extraction protocols were not specifically designed for label-free MS. While label-free quantification has its advantages, it is also very susceptible to technical variation. Here, we adjust an established histone extraction protocol according to general label-free MS guidelines with a specific focus on minimizing sample handling. These protocols are first evaluated using SDS-PAGE. Hereafter, a selection of extraction protocols was used in a complete histone workflow for label-free MS. All protocols display nearly identical relative quantification of hPTMs. We thus show that, depending on the cell type under investigation and at the cost of some additional contaminating proteins, minimizing sample handling can be done during histone isolation. This allows analyzing bigger sample batches, leads to reduced technical variation and minimizes the chance of in vitro alterations to the hPTM snapshot. Overall, these results allow researchers to determine the best protocol depending on the resources and goal of their specific study. Data are available via ProteomeXchange with identifier PXD002885.

The proteomic landscape of renal tumors.

INTRODUCTION: Renal cell carcinoma (RCC) is the most fatal of the common urologic cancers, with approximately 35% of patients dying within 5 years following diagnosis. Therefore, there is a need for non-invasive markers that are capable of detecting and determining the severity of small renal masses at an early stage in order to tailor treatment and follow-up. Proteomic studies have proved to be very useful in the study of tumors. Areas covered: In this review, we will detail the current knowledge obtained by the different proteomic approaches, focusing on MS-based strategies, used to investigate RCC biology in order to identify diagnostic, prognostic and predictive biomarkers on tissue, cultured cells and biological fluids. Expert commentary: Currently, no reliable biomarkers or targets for RCC have been translated into the clinical setting. Moreover, despite the efforts of proteomics and other -omics disciplines, only a small number of them have been observed as shared targets between the different analytical platforms and biological specimens. The difficulty to define a specific molecular pattern for RCC and its subtypes highlights a peculiar profile and a heterogeneity that must be taken into account in future studies.

Accelerating wavefunction in density-functional-theory embedding by truncating the active basis set.

Methods where an accurate wavefunction is embedded in a density-functional description of the surrounding environment have recently been simplified through the use of a projection operator to ensure orthogonality of orbital subspaces. Projector embedding already offers significant performance gains over conventional post-Hartree-Fock methods by reducing the number of correlated occupied orbitals. However, in our first applications of the method, we used the atomic-orbital basis for the full system, even for the correlated wavefunction calculation in a small, active subsystem. Here, we further develop our method for truncating the atomic-orbital basis to include only functions within or close to the active subsystem. The number of atomic orbitals in a calculation on a fixed active subsystem becomes asymptotically independent of the size of the environment, producing the required O(N(0)) scaling of cost of the calculation in the active subsystem, and accuracy is controlled by a single parameter. The applicability of this approach is demonstrated for the embedded many-body expansion of binding energies of water hexamers and calculation of reaction barriers of SN2 substitution of fluorine by chlorine in α-fluoroalkanes.

Comparison of 3 Different Therapeutic Particles in Radioembolization of Locally Advanced Intrahepatic Cholangiocarcinoma.

Our objective was to compare 3 different therapeutic particles used for radioembolization in locally advanced intrahepatic cholangiocarcinoma. Methods: 90Y-glass, 90Y-resin, and 166Ho-labeled poly(l-lactic acid) microsphere prescribed activity was calculated as per manufacturer recommendations. Posttreatment quantitative 90Y PET/CT and quantitative 166Ho SPECT/CT were used to determine tumor-absorbed dose, whole-normal-liver-absorbed dose, treated-normal-liver-absorbed dose, tumor-to-nontumor ratio, lung-absorbed dose, and lung shunt fraction. Response was assessed using RECIST 1.1 and the [18F]FDG PET-based change in total lesion glycolysis. Hepatotoxicity was assessed using the radioembolization-induced liver disease classification. Results: Six 90Y-glass, 8 90Y-resin, and 7 166Ho microsphere patients were included for analysis. The mean administered activity was 2.6 GBq for 90Y-glass, 1.5 GBq for 90Y-resin, and 7.0 GBq for 166Ho microspheres. Tumor-absorbed dose and treated-normal-liver-absorbed dose were significantly higher for 90Y-glass than for 90Y-resin and 166Ho microspheres (mean tumor-absorbed dose, 197 Gy for 90Y-glass vs. 73 Gy for 90Y-resin and 50 Gy for 166Ho; mean treated-normal-liver-absorbed dose, 79 Gy for 90Y-glass vs. 37 Gy for 90Y-resin and 31 Gy for 166Ho). The whole-normal-liver-absorbed dose and tumor-to-nontumor ratio did not significantly differ between the particles. All patients had a lung-absorbed dose under 30 Gy and a lung shunt fraction under 20%. The 3 groups showed similar toxicity and response according to RECIST 1.1 and [18F]FDG PET-based total lesion glycolysis changes. Conclusion: The therapeutic particles used for radioembolization differed from each other and showed significant differences in absorbed dose, whereas toxicity and response were similar for all groups. This finding emphasizes the need for separate dose constraints and dose targets for each particle.

Infectious Bovine Rhinotracheitis Post-Eradication Program in the Autonomous Province of Bolzano, Italy: A Retrospective Study on Potential Bovine Herpesvirus Type 2 Cross-Reactivity.

Bovine alphaherpesviruses, BoAHV, can cause respiratory, genital and neurological disorders. In particular, bovine alphaherpesvirus type 1 (BoAHV1) is one of the most significant ruminant pathogens worldwide and it can heavily damage the livestock industry. BoAHV1 can cause infectious bovine rhinotracheitis (IBR) along with fertility disorders. Bovine alphaherpesvirus type 2 (BoAHV2) can cause two different conditions as well: pseudo-lumpy skin disease (PSLD) and bovine herpetic mammillitis (BHM). The autonomous province of Bolzano (Italy) has adopted several strategies to control and eradicate IBR, and it was declared in 2000 to be IBR-free by the European Commission. Since 2001, a post-eradication monitoring program has overseen the serological analysis of bulk milk and, in the presence of a positive result, a follow-up examination is performed on the individual blood serum of all bovines older than 24 months that belong to bulk milk-positive herds. Despite the detection of positives in both bulk milk and serum samples, South Tyrol has been declared IBR-free, as these positives have never been confirmed through seroneutralization. Between 2014 and 2022, approximately 41,000 bulk milk (averaging 4300 samples/year) and 3229 serum samples were tested for BoAHV1. The aim of this study was to evaluate the post-eradication program for IBR with a particular focus on the potential cross-reactivity with BoAHV2; for this reason, serum samples were also tested for BoAHV2 antibodies. This study could be of great importance for those countries that submit herds to an IBR monitoring and eradication program; performing further analyses to confirm and explain false positive outcomes would increase the reliability of the obtained results.

Quantitative 177Lu SPECT/CT imaging for personalized dosimetry using a ring-shaped CZT-based camera.

BACKGROUND: Dosimetry after radiopharmaceutical therapy with 177Lu (177Lu-RPT) relies on quantitative SPECT/CT imaging, for which suitable reconstruction protocols are required. In this study, we characterized for the first time the quantitative performance of a ring-shaped CZT-based camera using two different reconstruction algorithms: an ordered subset expectation maximization (OSEM) and a block sequential regularized expectation maximization (BSREM) combined with noise reduction regularization. This study lays the foundations for the definition of a reconstruction protocol enabling accurate dosimetry for patients treated with 177Lu-RPT. METHODS: A series of 177Lu-filled phantoms were acquired on a StarGuide™ (GE HealthCare), with energy and scatter windows centred at 208 (± 6%) keV and 185 (± 5%) keV, respectively. Images were reconstructed with the manufacturer implementations of OSEM (GE-OSEM) and BSREM (Q.Clear) algorithms, and various combinations of iterations and subsets. Additionally, the manufacturer-recommended Q.Clear-based reconstruction protocol was evaluated. Quantification accuracy, measured as the difference between the SPECT-based and the radionuclide calibrator-based activity, and noise were evaluated in a large cylinder. Recovery coefficients (RCs) and spatial resolution were assessed in a NEMA IEC phantom with sphere inserts. The reconstruction protocols considered suitable for clinical applications were tested on a cohort of patients treated with [177Lu]Lu-PSMA-I&T. RESULTS: The accuracy of the activity from the cylinder, although affected by septal penetration, was < 10% for all reconstructions. Both algorithms featured improved spatial resolution and higher RCs with increasing updates at the cost of noise build-up, but Q.Clear outperformed GE-OSEM in reducing noise accumulation. When the reconstruction parameters were carefully selected, similar values for noise (~0.15), spatial resolution (~1 cm) and RCs were found, irrespective of the reconstruction algorithm. Analogue results were found in patients. CONCLUSIONS: Accurate activity quantification is possible when imaging 177Lu with StarGuide™. However, the impact of septal penetration requires further investigations. GE-OSEM is a valid alternative to the recommended Q.Clear reconstruction algorithm, featuring comparable performances assessed on phantoms and patients.

Automatic healthy liver segmentation for holmium-166 radioembolization dosimetry.

BACKGROUND: For safe and effective holmium-166 (166Ho) liver radioembolization, dosimetry is crucial and requires accurate healthy liver definition. The current clinical standard relies on manual segmentation and registration of a separately acquired contrast enhanced CT (CECT), a prone-to-error and time-consuming task. An alternative is offered by simultaneous imaging of 166Ho and technetium-99m stannous-phytate accumulating in healthy liver cells (166Ho-99mTc dual-isotope protocol). This study compares healthy liver segmentation performed with an automatic method using 99mTc images derived from a 166Ho-99mTc dual-isotope acquisition to the manual segmentation, focusing on healthy liver dosimetry and corresponding hepatotoxicity. Data from the prospective HEPAR PLuS study were used. Automatic healthy liver segmentation was obtained by thresholding the 99mTc image (no registration step required). Manual segmentation was performed on CECT and then manually registered to the SPECT/CT and subsequently to the corresponding 166Ho SPECT to compute absorbed dose in healthy liver. RESULTS: Thirty-one patients (66 procedures) were assessed. Manual segmentation and registration took a median of 30 min per patient, while automatic segmentation was instantaneous. Mean ± standard deviation of healthy liver absorbed dose was 18 ± 7 Gy and 20 ± 8 Gy for manual and automatic segmentations, respectively. Mean difference ± coefficient of reproducibility between healthy liver absorbed doses using the automatic versus manual segmentation was 2 ± 6 Gy. No correlation was found between mean absorbed dose in the healthy liver and hepatotoxicity. CONCLUSIONS: 166Ho-99mTc dual-isotope protocol can automatically segment the healthy liver without hampering the 166Ho dosimetry assessment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02067988. Registered 20 February 2014. https://clinicaltrials.gov/ct2/show/NCT02067988.

The carbonyl-lock mechanism underlying non-aromatic fluorescence in biological matter.

Challenging the basis of our chemical intuition, recent experimental evidence reveals the presence of a new type of intrinsic fluorescence in biomolecules that exists even in the absence of aromatic or electronically conjugated chemical compounds. The origin of this phenomenon has remained elusive so far. In the present study, we identify a mechanism underlying this new type of fluorescence in different biological aggregates. By employing non-adiabatic ab initio molecular dynamics simulations combined with a data-driven approach, we characterize the typical ultrafast non-radiative relaxation pathways active in non-fluorescent peptides. We show that the key vibrational mode for the non-radiative decay towards the ground state is the carbonyl elongation. Non-aromatic fluorescence appears to emerge from blocking this mode with strong local interactions such as hydrogen bonds. While we cannot rule out the existence of alternative non-aromatic fluorescence mechanisms in other systems, we demonstrate that this carbonyl-lock mechanism for trapping the excited state leads to the fluorescence yield increase observed experimentally, and set the stage for design principles to realize novel non-invasive biocompatible probes with applications in bioimaging, sensing, and biophotonics.

Transition-Based Constrained DFT for the Robust and Reliable Treatment of Excitations in Supramolecular Systems.

Despite the variety of available computational approaches, state-of-the-art methods for calculating excitation energies, such as time-dependent density functional theory (TDDFT), are computationally demanding and thus limited to moderate system sizes. Here, we introduce a new variation of constrained DFT (CDFT), wherein the constraint corresponds to a particular transition (T), or a combination of transitions, between occupied and virtual orbitals, rather than a region of the simulation space as in traditional CDFT. We compare T-CDFT with TDDFT and ΔSCF results for the low-lying excited states (S1 and T1) of a set of gas-phase acene molecules and OLED emitters and with reference results from the literature. At the PBE level of theory, T-CDFT outperforms ΔSCF for both classes of molecules, while also proving to be more robust. For the local excitations seen in the acenes, T-CDFT and TDDFT perform equally well. For the charge transfer (CT)-like excitations seen in the OLED molecules, T-CDFT also performs well, in contrast to the severe energy underestimation seen with TDDFT. In other words, T-CDFT is equally applicable to both local excitations and CT states, providing more reliable excitation energies at a much lower computational cost than TDDFT cost. T-CDFT is designed for large systems and has been implemented in the linear-scaling BigDFT code. It is therefore ideally suited for exploring the effects of explicit environments on excitation energies, paving the way for future simulations of excited states in complex realistic morphologies, such as those which occur in OLED materials.

Lung Dose Measured on Postradioembolization 90Y PET/CT and Incidence of Radiation Pneumonitis.

Radiation pneumonitis is a rare but possibly fatal side effect of 90Y radioembolization. It may occur 1-6 mo after therapy, if a significant part of the 90Y microspheres shunts to the lungs. In current clinical practice, a predicted lung dose greater than 30 Gy is considered a criterion to exclude patients from treatment. However, contrasting findings regarding the occurrence of radiation pneumonitis and lung dose were previously reported in the literature. In this study, the relationship between the lung dose and the eventual occurrence of radiation pneumonitis after 90Y radioembolization was investigated. Methods: We retrospectively analyzed 317 90Y liver radioembolization procedures performed during an 8-y period (February 2012 to September 2020). We calculated the predicted lung mean dose (LMD) using 99mTc-MAA planar scintigraphy (LMDMAA) acquired during the planning phase and left LMD (LMDY-90) using the 90Y PET/CT acquired after the treatment. For the lung dose computation, we used the left lung as the representative lung volume, to compensate for scatter from the liver moving in the craniocaudal direction because of breathing and mainly affecting the right lung. Results: In total, 272 patients underwent 90Y procedures, of which 63% were performed with glass microspheres and 37% with resin microspheres. The median injected activity was 1,974 MBq (range, 242-9,538 MBq). The median LMDMAA was 3.5 Gy (range, 0.2-89.0 Gy). For 14 procedures, LMDMAA was more than 30 Gy. Median LMDY-90 was 1 Gy (range, 0.0-22.1 Gy). No patients had an LMDY-90 of more than 30 Gy. Of the 3 patients with an LMDY-90 of more than 12 Gy, 2 patients (one with an LMDY-90 of 22.1 Gy and an LMDMAA of 89 Gy; the other with an LMDY-90 of 17.7 Gy and an LMDMAA of 34.1 Gy) developed radiation pneumonitis and consequently died. The third patient, with an LMDY-90 of 18.4 Gy (LMDMAA, 29.1 Gy), died 2 mo after treatment, before the imaging evaluation, because of progressive disease. Conclusion: The occurrence of radiation pneumonitis as a consequence of a lung shunt after 90Y radioembolization is rare (<1%). No radiation pneumonitis developed in patients with a measured LMDY-90 lower than 12 Gy.