Surgery and postoperative definitive radiotherapy for management of canine soft tissue sarcoma: a multi-institutional retrospective study of 272 dogs (2010-2020).

Objective: To report local progression and survival in dogs following surgery and postoperative definitive radiotherapy (dRT) for management of soft tissue sarcoma (STS) and to evaluate risk factors for local progression and survival.

Methods: Records were retrospectively reviewed at 9 referral hospitals for dogs managed with postoperative dRT between January 1, 2010, and January 1, 2020, following surgery for STS. Data related to presentation, surgery, dRT, systemic therapy, and outcome were abstracted.

Single Chelator-Minibody Theranostic Agents for Zr PET Imaging and Lu Radiopharmaceutical Therapy of PSMA-Expressing Prostate Cancer.

Here we describe an anti-prostate-specific membrane antigen (PSMA) minibody (IAB2MA) conjugated to an octadentate, macrocyclic chelator based on four 1-hydroxypyridin-2-one coordinating units (Lumi804 [L804]) labeled with Zr (PET imaging) and Lu (radiopharmaceutical therapy), with the goal of developing safer and more efficacious treatment options for prostate cancer. L804 was compared with the current gold standard chelators, DOTA and deferoxamine (DFO), conjugated to IAB2MA for radiolabeling with Lu and Zr in cell binding, preclinical biodistribution, imaging, dosimetry, and efficacy studies in the PSMA-positive PC3-PIP tumor-bearing mouse model of prostate cancer. Quantitative radiolabeling (>99% radiochemical yield) of L804-IAB2MA with Lu or Zr was achieved at ambient temperature in under 30 min, comparable to Zr labeling of DFO-IAB2MA.

Monte Carlo dosimetric analyses on the use ofY-IsoPet intratumoral therapy in canine subjects.

To investigate different dosimetric aspects ofY-IsoPet™ intratumoral therapy in canine soft tissue sarcomas, model the spatial spread of the gel post-injection, evaluate absorbed dose to clinical target volumes, and assess dose distributions and treatment efficacy.Six canine cases treated withY-IsoPet™ for soft tissue sarcoma at the Veterinary Health Center, University of Missouri are analyzed in this retrospective study. The dogs received intratumoral IsoPet™ injections, following a grid pattern to achieve a near-uniform dose distribution in the clinical target volume.

Translational History and Hope of Immunotherapy of Canine Tumors.

Companion dogs have served an important role in cancer immunotherapy research. Sharing similar environments and diets with humans, dogs naturally develop many of the same cancers. These shared exposures, coupled with dogs' diverse genetic makeup, make them ideal subjects for studying cancer therapies.

Sodium iodide symporter immunolabelling as a predictor of clinical iodide uptake in canine thyroid carcinoma: A preliminary study.

Thyroid follicular tumours may take up iodide via the sodium-iodide symporter. Knowledge of iodide uptake could then allow treatment with I-131 in dogs with high-risk tumours. The objective of this study was to determine the relationship between clinically detectable iodide uptake (as determined by scintigraphy and/or thyroxine concentrations) and sodium iodide symporter immunohistochemical labelling on histologically fixed thyroid tumours.

The role of companion animal models in radiopharmaceutical development and translation.

Advancements in molecular imaging and drug targeting have created a renaissance in the development of radiopharmaceuticals for therapy and theranostics. While some radiopharmaceuticals, such as Na[I]I, have been used clinically for decades, new agents are being approved using small-molecules, peptides, and antibodies for targeting. As these agents are being developed, the need to understand dosimetry and biologic effects of the systemically delivered radiotherapy becomes more important, particularly as highly potent radiopharmaceuticals using targeted alpha therapy become clinically utilized.

Effects of neoadjuvant zoledronate and radiation therapy on cell survival, cell cycle distribution, and clinical status in canine osteosarcoma.

Introduction: Zoledronic acid (ZOL) is a third-generation bisphosphonate with a higher affinity for bone resorption areas than earlier bisphosphonates (i.e., pamidronate, PAM).

Pretargeted PET of Osteodestructive Lesions in Dogs.

The last decade has witnessed the creation of a highly effective approach to pretargeting based on the inverse electron demand Diels-Alder (IEDDA) click ligation between tetrazine (Tz) and -cyclooctene (TCO). Despite the steady progression of this technology toward the clinic, concerns have persisted regarding whether this chemistry will work in humans given their larger size and blood volume. In this work, we describe the use of a Cu-labeled Tz radioligand ([Cu]Cu-SarAr-Tz) and a TCO-bearing bisphosphonate (TCO-BP) for the pretargeted positron emission tomography (PET) imaging of osteodestructive lesions in a large animal model: companion dogs.

Fracture rate and time to fracture in dogs with appendicular osteosarcoma receiving finely fractionated compared to coarsely fractionated radiation therapy: A single institution study.

Background: Radiation therapy (RT) is used for local pain alleviation in dogs with appendicular osteosarcoma (OS), especially among dogs that are poor surgical candidates for amputation. However, many historical reports of fractionated protocols lack time to fracture and fracture rates.

Objectives: The primary objectives of this retrospective study were to determine fracture rate and time to fracture of dogs receiving RT (coarse or fine fractionated) for appendicular OS.

A Pilot Study of Cancer-Induced Bone Pain Using Validated Owner Questionnaires, Serum N-Telopeptide Concentration, Kinetic Analysis, and PET/CT.

Cancer-induced bone pain, despite its frequency and severity, is a poorly understood phenomenon in people and animals. Despite excitement regarding translational osteosarcoma studies, there is a lack of attention toward examining cancer pain in dogs. In this pilot study, we used a multimodal pain assessment methodology to evaluate pain relief after therapeutic intervention in dogs with primary bone cancer.

Biodistribution and image characteristics of I-positron emission tomography in dogs with neuroendocrine neoplasia.

Radioactive iodine is frequently used for staging of human thyroid carcinomas. Iodine-124 scans performed using position emission tomography (PET) allow for more precise dosimetry of therapeutic radioiodine. The distribution of I-124 has not previously been described in veterinary medicine.

Paired 18F-Fluorodeoxyglucose (18F-FDG), and 64Cu-Copper(II)-diacetyl-bis(N(4)-methylthiosemicarbazone) (64Cu-ATSM) PET Scans in Dogs with Spontaneous Tumors and Evaluation for Hypoxia-Directed Therapy.

Hypoxia is associated with neoplastic tissue, protecting cancer cells from death by irradiation and chemotherapy. Identification of hypoxic volume of tumors could optimize patient selection for hypoxia-directed medical, immunological, and radiation therapies. Clostridium novyi-NT (CNV-NT) is an oncolytic bacterium derived from attenuated wild-type Clostridium novyi spores, which germinates exclusively in the anaerobic core of tumors with low-oxygen content.

Immune cell β-adrenergic receptors contribute to the development of heart failure.

β-Adrenergic receptors (βARs) regulate normal and pathophysiological heart function through their impact on contractility. βARs are also regulators of immune function where they play a unique role depending on the disease condition and immune cell type. Emerging evidence suggests an important role for the βAR subtype in regulating remodeling in the pathological heart; however, the importance of these responses has never been examined.

A 3D-printed Apparatus for Imaging Multiple Rats Simultaneously.

CT (computerized tomography) is a necessary imaging modality for cancer staging and disease monitoring. Rodent models of cancer are commonly studied prior to human clinical trials, but CT in rodents can be difficult due to their small size and constant movement, which necessitates general anesthesia. Because microCT equipment is not always available, clinical CT may be a viable alternative.

Nasal angiofibroma treatment outcome using intensity-modulated radiation therapy in a dog.

A 6-year-old dog presented with a modified Adams stage 3 angiofibroma of the right nasal cavity, causing fluid accumulation along the right frontal sinus. Treatment consisted of step-and-shoot intensity-modulated radiation therapy in 12 daily treatments of 3.5 Gy, for a total dose of 42 Gy to 95% of the planning target volume.

β2-Adrenergic Receptors Increase Cardiac Fibroblast Proliferation Through the Gαs/ERK1/2-Dependent Secretion of Interleukin-6.

Fibroblasts are an important resident cell population in the heart involved in maintaining homeostasis and structure during normal conditions. They are also crucial in disease states for sensing signals and initiating the appropriate repair responses to maintain the structural integrity of the heart. This sentinel role of cardiac fibroblasts occurs, in part, through their ability to secrete cytokines.

Detection of silent reflux events by nuclear scintigraphy in healthy dogs.

Background: Reflux and aspiration in people are associated with respiratory disease, whereas approximately 50% of healthy adults microaspirate without apparent consequence. In dogs, analogous information is lacking.

Hypothesis: Healthy dogs commonly have gastroesophageal reflux and a proportion of these dogs will have laryngopharyngeal reflux with silent aspiration.

Direct Interstitial Treatment of Solid Tumors Using an Injectable Yttrium-90-Polymer Composite.

Yttrium-90 (Y)-polymer composite (radiogel) may be administered directly into cancerous tissues to deliver highly localized beta radiation for therapy. In a dose-escalation study, the authors investigated the feasibility of treating feline and canine soft-tissue sarcomas as a model for nonresectable solid tumors in humans to gain clinical experience and to identify optimal methods for placing the composite uniformly within target tumor tissue. Five cats (Washington State University) and three dogs (University of Missouri) were selected for treatment from among veterinary clinic patients presenting with subcutaneous soft-tissue sarcomas.

Use of computed tomography and radiation therapy planning software to develop a novel formula for body surface area calculation in dogs.

Background: Body surface area (BSA) can reflect metabolic rate that might normalize dosing of chemotherapeutics across widely variable weights within a species. The current BSA formula for dogs lacks height, length, and body condition.

Hypothesis: Computed tomography (CT) imaging will allow inclusion of morphometric variables in allometric modeling of BSA in dogs resulting in an improved formula for BSA estimation.

Demonstration of the bactericidal effects of the boron neutron capture reaction.

This pilot study represents a paradigm shift, using BNCT for the treatment of bacterial overgrowth on surgically implanted medical devices. In this study, titanium diboride disks were inoculated with S. aureus and irradiated in a thermal neutron beam.

Validation and Comparison of the Therapeutic Efficacy of Boron Neutron Capture Therapy Mediated By Boron-Rich Liposomes in Multiple Murine Tumor Models.

Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. Mice were implanted with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH(CH)-7,8-CBH] in the lipid bilayer and encapsulated Na[1-(2`-BH)-2-NHBH] within the liposomal core. Mice were irradiated 30 hours after the second injection in a thermal neutron beam for various lengths of time.

Use of an electronic brachytherapy surface applicator to treat an epiglottal fibrosarcoma in a dog.

Presented is the case of an epiglottal fibrosarcoma in a dog. The location of the mass resulted in challenges in the delivery of adequate dose to the tumor, and herein we describe the treatment using an electronic brachytherapy source. The treatment consisted of four Gy fractions, twice daily for a total of 10 fractions (40 Gy total).

Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model.

The application of boron neutron capture therapy (BNCT) mediated by liposomes containing (10)B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na3[ae-B20H17NH3] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.

Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes.

The application of boron neutron capture therapy (BNCT) following liposomal delivery of a (10)B-enriched polyhedral borane and a carborane against mouse mammary adenocarcinoma solid tumors was investigated. Unilamellar liposomes with a mean diameter of 134 nm or less, composed of an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine and incorporating Na3[1-(2'-B10H9)-2-NH3B10H8] in the aqueous interior and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer, were injected into the tail veins of female BALB/c mice bearing right flank EMT6 tumors. Biodistribution studies indicated that two identical injections given 24 h apart resulted in tumor boron levels exceeding 67 µg/g tumor at 54 h--with tumor/blood boron ratios being greatest at 96 h (5.