Dosimetry of a Novel Indium-Labeled Anti-P-Cadherin Monoclonal Antibody (FF-21101) in Non-Human Primates.

P-cadherin is associated with a wide range of tumor types, making it an attractive therapeutic target. FF-21101 is a human-mouse chimeric monoclonal antibody (mAb) directed against human P-cadherin, which has been radioconjugated with indium-111 (In) utilizing a DOTA chelator. We investigated the biodistribution of FF-21101(In) in cynomolgus macaques and extrapolated the results to estimate internal radiation doses of In- and yttrium-90 (Y)-FF-21101 for targeted radioimmunotherapy in humans.

Understanding entrance-air-kerma as a quality-control metric for dual-energy x-ray absorptiometry.

Purpose: The low exposures, unique x-ray beam geometry, and scanning design in dual-energy x-ray absorptiometry (DXA) make measurement and quality-control strategies different from traditional x-ray equipment. This study examines the dependence of measured entrance-air-kerma (EAK) on both dose sensor type and scan length. The feasibility of using EAK to compare scanner output between different scan modes, individual scanners, and scanner platforms was also established.

A novel dosing strategy of del Nido cardioplegia in aortic surgery.

Objective: While del Nido (DN) cardioplegia is increasingly used in cardiac surgery, knowledge is limited in its safety profile for operations with prolonged crossclamp time (CCT). We have introduced a unique redosing strategy for aortic surgery: all operations use DN with a 1000-mL initiation dose (750 mL antegrade, 250 mL retrograde) composed of 1:4 blood:DN crystalloid. At 90 minutes CCT and every 30 minutes thereafter, a 250-mL dose was introduced retrograde in a 4:1 ("reverse") ratio.

A Single Injection of NTG-101 Reduces the Expression of Pain-Related Neurotrophins in a Canine Model of Degenerative Disc Disease.

Tissue sources of pain emanating from degenerative discs remains incompletely understood. Canine intervertebral discs (IVDs) were needle puncture injured, 4-weeks later injected with either phosphate-buffered saline (PBS) or NTG-101, harvested after an additional fourteen weeks and then histologically evaluated for the expression of NGFr, BDNF, TrkB and CALCRL proteins. Quantification was performed using the HALO automated cell-counting scoring platform.

Current Status of the Instructional Cues Provided by Notochordal Cells in Novel Disc Repair Strategies.

Numerous publications over the past 22 years, beginning with a seminal paper by Aguiar et al., have demonstrated the ability of notochordal cell-secreted factors to confer anabolic effects upon intervertebral disc (IVD) cells. Since this seminal paper, other scientific publications have demonstrated that notochordal cells secrete soluble factors that can induce anti-inflammatory, pro-anabolic and anti-cell death effects upon IVD nucleus pulposus (NP) cells in vitro and in vivo, direct human bone marrow-derived mesenchymal stem cells toward an IVD NP-like phenotype and repel neurite ingrowth.

Cancer Incidence and Mortality Among Fighter Aviators in the United States Air Force.

Objective: This study sought to clarify cancer risk in fighter aviators.

Methods: US Air Force officers who served between 1970 and 2004 were followed through 2018 for incidence and mortality of 10 cancers: colon and rectum; pancreas; melanoma skin; prostate; testis; urinary bladder; kidney and renal pelvis; brain and other nervous system; thyroid; and non-Hodgkin lymphoma. Fighter aviators were compared with other officers and the general US population.

Automated Contouring of Contrast and Noncontrast Computed Tomography Liver Images With Fully Convolutional Networks.

Purpose: The deformable nature of the liver can make focal treatment challenging and is not adequately addressed with simple rigid registration techniques. More advanced registration techniques can take deformations into account (eg, biomechanical modeling) but require segmentations of the whole liver for each scan, which is a time-intensive process. We hypothesize that fully convolutional networks can be used to rapidly and accurately autosegment the liver, removing the temporal bottleneck for biomechanical modeling.

Phase I Study of P-cadherin-targeted Radioimmunotherapy with Y-FF-21101 Monoclonal Antibody in Solid Tumors.

Purpose: Y-FF-21101 is an Yttrium-90-conjugated, chimeric mAb that is highly specific for binding to human placental (P)-cadherin, a cell-to-cell adhesion molecule overexpressed and associated with cancer invasion and metastatic dissemination in many cancer types. We report the clinical activity of Y-FF-21101 in a first-in-human phase I study in patients with advanced solid tumors.

Patients And Methods: The safety and efficacy of Y-FF-21101 were evaluated in a phase I 3+3 dose-escalation study in patients with advanced solid tumors ( = 15) over a dose range of 5-25 mCi/m.

An open-label, single-arm pilot study of EUS-guided brachytherapy with phosphorus-32 microparticles in combination with gemcitabine +/- nab-paclitaxel in unresectable locally advanced pancreatic cancer (OncoPaC-1): Technical details and study protocol.

Current treatment options for patients with unresectable locally advanced pancreatic cancer (LAPC) include chemotherapy alone or followed by chemoradiation or stereotactic body radiotherapy. However, the prognosis for these patients remains poor, with a median overall survival <12 months. Therefore, novel treatment options are needed.

Targeted Radionuclide Therapy for Patients with Metastatic Pheochromocytoma and Paraganglioma: From Low-Specific-Activity to High-Specific-Activity Iodine-131 Metaiodobenzylguanidine.

Low-specific-activity iodine-131-radiolabeled metaiodobenzylguanidine (I-131-MIBG) was introduced last century as a potential systemic therapy for patients with malignant pheochromocytomas and paragangliomas. Collective information derived from mainly retrospective studies has suggested that 30-40% of patients with these tumors benefit from this treatment. A low index of radioactivity, lack of therapeutic standardization, and toxicity associated with intermediate to high activities (absorbed radiation doses) has prevented the implementation of I-131-MIBG's in clinical practice.

Preoperative PET/CT does not accurately detect extrauterine disease in patients with newly diagnosed high-risk endometrial cancer: A prospective study.

Background: The identification of extrauterine disease is critical to the management of patients with high-risk endometrial cancer. The purpose of the current study was to determine the accuracy of preoperative positron emission tomography (PET)/computed tomography (CT) in the detection of extrauterine disease.

Methods: Women with high-risk endometrial cancer were enrolled prospectively and underwent preoperative PET/CT followed by surgery, including sentinel lymph node biopsy and lymphadenectomy.

Effectiveness of a direct-to-consumer written health education program in the reduction of benzodiazepine and sedative-hypnotic use in an elderly population at a single Veterans Affairs medical center.

Introduction: The use of benzodiazepines and sedative-hypnotics in the elderly is associated with a significant risk of delirium, falls, fractures, cognitive impairment, and motor vehicle accidents. This quality improvement project applies a direct-to-consumer intervention to an elderly veteran population to reduce the use of these medications.

Methods: Patients aged 75 and older currently taking a benzodiazepine and/or a sedative-hypnotic were included in the project.

A personalized, Monte Carlo-based method for internal dosimetric evaluation of radiopharmaceuticals in children.

Purpose: Herein, we introduce a methodology for estimating the absorbed dose in organs at risk that is based on specified clinically derived radiopharmaceutical biodistributions and personalized anatomical characteristics.

Methods: To evaluate the proposed methodology, we used realistic Monte Carlo (MC) simulations and computational pediatric models to calculate a parameter called in this work the "specific absorbed dose rate" (SADR). The SADR is a unique quantitative metric in that it is specific to a particular organ.

Updated Results of Rituximab Pre- and Post-BEAM with or without Yttrium Ibritumomab Tiuxetan during Autologous Transplant for Diffuse Large B-cell Lymphoma.

We evaluated the effect on long-term survival of adding rituximab (R) to BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning with or without yttrium-90 ibritumomab tiuxetan (YIT) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem cell transplant (ASCT). Patients were enrolled on three consecutive phase II clinical trials. Patients received two doses of rituximab (375 and 1,000 mg/m) during mobilization of stem cells, followed by 1,000 mg/m on days +1 and +8 after ASCT with R-BEAM or YIT-R-BEAM (YIT dose of 0.

AAPM medical physics practice guideline 6.a.: Performance characteristics of radiation dose index monitoring systems.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States.

Enhancement in Organic Photovoltaics Controlled by the Interplay between Charge-Transfer Excitons and Surface Plasmons.

In this work, we investigate plasmonic enhancement in poly(3-hexylthiophene):phenyl-C61-butyric acid methyl ester organic photovoltaics (OPVs) by integrating shape- and size-controlled bimetallic gold core-silver shell nanocrystals (Au-Ag NCs) into the poly(3,4-ethylenedioxythiophene):polystyrene sulfonate hole-transport layer. We observed that the best-performing Au-Ag NC-incorporated OPVs improved the power conversion efficiency by 9% via a broadband increase in photocurrent throughout the visible spectrum. Our experimental and computational results suggest that the observed photocurrent enhancement in plasmonic OPVs originates from both enhanced absorption and improved exciton dissociation and charge collection.

Qualitative and quantitative comparison of gated blood pool single photon emission computed tomography using low-energy high-resolution and SMARTZOOM collimation.

Objective: The aim of this study was to assess the feasibility of IQ-SPECT gated blood pool (MUGA) under conditions of decreased scan time (ST).

Patients And Methods: Ten patients underwent routine 26-min, two-view planar, followed by LEHR and IQ-SPECT MUGA, on a Siemens dual-head Symbia scanner. Six 'back and forth' 4-min SPECT scans were summed into 4-, 8-, 12-, 16-, 20-, and 24-min equivalent scans, and reconstructed iteratively (IQ-SPECT and LEHR) and with FBP (LEHR).

Evaluation of a deterministic grid-based Boltzmann solver (GBBS) for voxel-level absorbed dose calculations in nuclear medicine.

To evaluate the 3D Grid-based Boltzmann Solver (GBBS) code ATTILA (®) for coupled electron and photon transport in the nuclear medicine energy regime for electron (beta, Auger and internal conversion electrons) and photon (gamma, x-ray) sources. Codes rewritten based on ATTILA are used clinically for both high-energy photon teletherapy and (192)Ir sealed source brachytherapy; little information exists for using the GBBS to calculate voxel-level absorbed doses in nuclear medicine. We compared DOSXYZnrc Monte Carlo (MC) with published voxel-S-values to establish MC as truth.

Verification of I-125 brachytherapy source strength for use in radioactive seed localization procedures.

A general-purpose nuclear medicine dose calibrator was assessed as a potential replacement for a dedicated air-communicating well-type ionization chamber (brachytherapy source strength verification instrument) for (125)I seed source strength verification for radioactive seed localization, where less stringent accuracy tolerances may be acceptable. The accuracy, precision and reproducibility of the dose calibrator were measured and compared to regulatory requirements. The results of this work indicate that a dose calibrator can be used for (125)I seed source strength verification for radioactive seed localization.

Skeletal Tumor Burden on Baseline 18F-Fluoride PET/CT Predicts Bone Marrow Failure After 223Ra Therapy.

Purpose: Determine if skeletal tumor burden on 18F-fluoride PET/CT (fluoride PET/CT) predicts the risk of bone marrow failure (BMF) after 223Ra dichloride therapy (223Ra).

Methods: Forty-one metastatic prostate cancer patients (43-89 years old; mean, 71 ± 9 years.) underwent fluoride PET/CT prior to 223Ra.

Corrosion resistant three-dimensional nanotextured silicon for water photo-oxidation.

We demonstrate the ability to chemically transform bulk silicon into a nanotextured surface that exhibits excellent electrochemical stability in aqueous conditions for water photo-oxidation. Conformal defective graphene coatings on nanotextured silicon formed by thermal treatment enable over 50× corrosion resistance in aqueous electrolytes based upon Tafel analysis and impedance spectroscopy. This enables nanotextured silicon as an effective oxygen-evolution photoanode for water splitting with saturation current density measured near 35 mA cm(-2) under 100 mW cm(-2) (1 sun) illumination.

The biological basis of degenerative disc disease: proteomic and biomechanical analysis of the canine intervertebral disc.

Introduction: In the present study, we sought to quantify and contrast the secretome and biomechanical properties of the non-chondrodystrophic (NCD) and chondrodystrophic (CD) canine intervertebral disc (IVD) nucleus pulposus (NP).

Methods: We used iTRAQ proteomic methods to quantify the secretome of both CD and NCD NP. Differential levels of proteins detected were further verified using immunohistochemistry, Western blotting, and proteoglycan extraction in order to evaluate the integrity of the small leucine-rich proteoglycans (SLRPs) decorin and biglycan.