At-Labeled Anti-CD45 Antibody as a Nonmyeloablative Conditioning for Canine DLA-Haploidentical Stem Cell Transplantation.

The α-emitter At deposits a high amount of energy within a few cell diameters, resulting in irreparable DNA double-strand breaks while minimizing off-target toxicity. We investigated the use of the At-labeled anti-CD45 monoclonal antibody (mAb) At-CD45-B10 as a nonmyeloablative conditioning regimen for dog-leukocyte-antigen-haploidentical hematopoietic cell transplantation. Seventeen healthy dogs were injected with either a 0.

Pilot study of humanized glypican-3-targeted zirconium-89 immuno-positron emission tomography for hepatocellular carcinoma.

Purpose: Glypican-3 (GPC3)-targeted radioisotope immuno-positron emission tomography (immunoPET) may lead to earlier and more accurate diagnosis of hepatocellular carcinoma (HCC), thus facilitating curative treatment, decreasing early recurrence, and enhancing patient survival. We previously demonstrated reliable HCC detection using a zirconium-89-labeled murine anti-GPC3 antibody (89Zr-αGPC3M) for immunoPET. This study evaluated the efficacy of the humanized antibody successor (αGPC3H) to further clinical translation of a GPC3-based theranostic for HCC.

Predicting Acute Median Neuropathy in Perilunate Injuries.

Purpose: Perilunate fracture dislocation (PLFD) injuries are associated with the development of acute carpal tunnel syndrome (CTS). The purpose of our study was to identify the factors that increase the likelihood of developing CTS in patients with PLFD. Additionally, we attempted to classify patients who did not initially undergo carpal tunnel release (CTR) at the time of injury but eventually underwent CTR within the follow-up period.

Trends in orthopaedic surgery resident case volume and the impact of COVID-19 on resident education.

Introduction: COVID-19 had numerous objective and subjective effects on resident physician education. We intended to examine objective changes in orthopedic education that occurred during the COVID pandemic and other trends from 2018 to 2022 by analyzing surgical case logs from Accreditation Counsel for Graduate Medical Education (ACGME) approved American orthopedics programs. We hypothesized that surgical case load during the COVID pandemic would remain similar to pre-pandemic levels and case logs would show a general upward trend.

Targeted Radiation Delivery before Haploidentical HCT for High-risk Leukemia or MDS Patients Yields Long-term Survivors.

Purpose: Hematopoietic cell transplantation (HCT) has curative potential for myeloid malignancies, though many patients cannot tolerate myeloablative conditioning with high-dose chemotherapy alone or with total-body irradiation (TBI). Here we report long-term outcomes from a phase I/II study using iodine-131 (131I)-anti-CD45 antibody BC8 combined with nonmyeloablative conditioning prior to HLA-haploidentical HCT in adults with high-risk relapsed/ refractory acute myeloid or lymphoid leukemia (AML or ALL), or myelodysplastic syndrome (MDS; ClinicalTrials.gov, NCT00589316).

Eponyms Describing Soft Tissue Pathologies in Orthopedic Hand Surgery.

Orthopedic surgery literature utilizes numerous eponyms, and they have become commonplace among orthopedic surgeons and the general public alike. These eponyms can have important historical implications and their history is often overlooked by the physicians using such terms. This paper seeks to specifically explore the origins of eponyms in orthopedic soft tissue diseases involving the upper extremity.

External Fixation Prior to Fasciectomy Leads to Substantial Improvement of Advanced Dupuytren's PIP Contractures at Mean Follow-up 15 Months.

Background: The Digit Widget is an external fixation device that can be used to reverse proximal interphalangeal joint (PIPJ) contractures in the hand. Our hypothesis is that usage of the Digit Widget prior to fasciectomy in patients with severe Dupuytren's proximal interphalangeal (PIP) contractures will result in short-term improvement and maintenance of the PIPJ contracture after fasciectomy.

Methods: Patients who underwent placement of the Digit Widget soft tissue distractor prior to fasciectomy for Dupuytren's disease were identified between January 2015 and December 2018.

Development of de Quervain Tenosynovitis After Distal Radius Fracture.

Background: We sought to determine the risk factors for the development of de Quervain tenosynovitis after distal radius fractures. Our hypothesis is that longer periods of immobilization and higher-energy fracture patterns will correlate with the development of de Quervain tenosynovitis.

Methods: This is a 10-year retrospective study of 1451 consecutive patients with distal radius fractures presenting to a large academic institution.

Design and synthesis of astatinated benzothiazole compounds for their potential use in Targeted Alpha Therapy (TAT) strategies to treat Alzheimer's disease-associated amyloid plaques.

Alzheimer's disease (AD) is a terminal neurodegenerative disease characterized by the buildup of amyloid fibrils, amorphous aggregates and tauopathies. Several treatment modalities, which rely on various biological processes to reduce disease burden, have been largely ineffective at treating Alzheimer's disease. Targeted alpha therapy (TAT) has demonstrated positive results in the treatment of cancer.

Small-scale (sub-organ and cellular level) alpha-particle dosimetry methods using an iQID digital autoradiography imaging system.

Targeted radiopharmaceutical therapy with alpha-particle emitters (αRPT) is advantageous in cancer treatment because the short range and high local energy deposition of alpha particles enable precise radiation delivery and efficient tumor cell killing. However, these properties create sub-organ dose deposition effects that are not easily characterized by direct gamma-ray imaging (PET or SPECT). We present a computational procedure to determine the spatial distribution of absorbed dose from alpha-emitting radionuclides in tissues using digital autoradiography activity images from an ionizing-radiation quantum imaging detector (iQID).

Oxidation of -[I]Iodobenzoic Acid and -[At]Astatobenzoic Acid Derivatives and Evaluation In Vivo.

The alpha particle-emitting radionuclide astatine-211 (At) is of interest for targeted radiotherapy; however, low in vivo stability of many At-labeled cancer-targeting molecules has limited its potential. As an alternative labeling method, we evaluated whether a specific type of astatinated aryl compound that has the At atom in a higher oxidation state might be stable to in vivo deastatination. In the research effort, para-iodobenzoic acid methyl ester and dPEG-amino acid methyl ester derivatives were prepared as HPLC standards.

Development and biodistribution studies of As-labeled trithiol RM2 bioconjugates for prostate cancer: Comparison of [As]As-trithiol-Ser-Ser-RM2 vs. [As]As-trithiol-Glu-Ser-RM2.

Introduction: Recent progress with the production of As (2.49 Mev β (64%), 3.33 Mev β (16%), 834 keV γ (81%), t: 26 h) and As (0.

Harnessing -Emitting Radionuclides for Therapy: Radiolabeling Method Review.

Targeted α-therapy (TAT) is an emerging powerful tool treating late-stage cancers for which therapeutic options are limited. At the core of TAT are targeted radiopharmaceuticals, where isotopes are paired with targeting vectors to enable tissue- or cell-specific delivery of α-emitters. DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and DTPA (diethylenetriamine pentaacetic acid) are commonly used to chelate metallic radionuclides but have limitations.

Production and Supply of α-Particle-Emitting Radionuclides for Targeted α-Therapy.

Encouraging results from targeted α-therapy have received significant attention from academia and industry. However, the limited availability of suitable radionuclides has hampered widespread translation and application. In the present review, we discuss the most promising candidates for clinical application and the state of the art of their production and supply.

Automated identification of glomeruli and synchronised review of special stains in renal biopsies by machine learning and slide registration: a cross-institutional study.

Aims: Machine learning in digital pathology can improve efficiency and accuracy via prescreening with automated feature identification. Studies using uniform histological material have shown promise. Generalised application requires validation on slides from multiple institutions.

Addition of Astatine-211-Labeled Anti-CD45 Antibody to TBI as Conditioning for DLA-Identical Marrow Transplantation: A Novel Strategy to Overcome Graft Rejection in a Canine Presensitization Model: "Radioimmunotherapy to Overcome Transfusion-Induced Sensitization".

In a canine model of presensitization using donor blood transfusions, 100% of historical control dogs receiving 9.2 Gy total body irradiation (TBI) conditioning before dog leukocyte antigen (DLA)-identical marrow grafts had graft rejection. In this presensitization model, we investigated whether the addition of monoclonal antibody (mAb)-based targeted radioimmunotherapy (RIT) with astatine-211 (At) to TBI could overcome graft rejection.

Glypican-3 targeted delivery of Zr and Y as a theranostic radionuclide platform for hepatocellular carcinoma.

Glypican-3 (GPC3) is a tumor associated antigen expressed by hepatocellular carcinoma (HCC) cells. This preclinical study evaluated the efficacy of a theranostic platform using a GPC3-targeting antibody αGPC3 conjugated to zirconium-89 (Zr) and yttrium-90 (Y) to identify, treat, and assess treatment response in a murine model of HCC. A murine orthotopic xenograft model of HCC was generated.