Background: Osteosarcoma (OS) has an overall patient survival rate of ~70% with no significant improvements in the last two decades, and novel effective treatments are needed. OS in companion dogs is phenotypically close to human OS, which makes a comparative oncology approach to developing new treatments for OS very attractive. We have recently created a novel human antibody, IF3 to IGF2R, which binds to this receptor on both human and canine OS tumors. Here, we evaluated the efficacy and safety of radioimmunotherapy with ¹⁷⁷Lu-labeled IF3 of mice bearing canine-patient-derived tumors and performed canine and human dosimetry calculations. Methods: Biodistribution and microSPECT/CT imaging with ¹¹¹In-IF3 was performed in mice bearing canine OS Gracie tumors, and canine and human dosimetry calculations were performed based on these results. RIT of Gracie-tumor-bearing mice was completed with ¹⁷⁷Lu-IF3. Results: Biodistribution and imaging showed a high uptake of ¹¹¹In-IF3 in the tumor and spleen. Dosimetry identified the tumor, spleen and pancreas as the organs with the highest uptake. RIT was very effective in abrogating tumor growth in mice with some spleen-associated toxicity. Conclusions: These results demonstrate that RIT with ¹⁷⁷Lu-IF3 targeting IGF2R on experimental canine OS tumors effectively decreases tumor growth. However, because of the limitations of murine models, careful evaluation of the possible toxicity of this treatment should be performed via nuclear imaging and image-based dosimetry in healthy dogs before clinical trials in companion dogs with OS can be attempted.

Etiological and genetic drivers of osteosarcoma (OS) are not well studied and vary from one tumor to another; making it challenging to pursue conventional targeted therapy. Recent studies have shown that cation independent mannose-6-phosphate/insulin-like growth factor-2 receptor (IGF2R) is consistently overexpressed in almost all of standard and patient-derived OS cell lines, making it an ideal therapeutic target for development of antibody-based drugs. Monoclonal antibodies, targeting IGF2R, can be conjugated with alpha- or beta-emitter radionuclides to deliver cytocidal doses of radiation to target IGF2R expression in OS. This approach known as radioimmunotherapy (RIT) can therefore be developed as a novel treatment for OS. In addition, OS is one of the common cancers in companion dogs and very closely resembles human OS in clinical presentation and molecular aberrations. In this study, we have developed human antibodies that cross-react with similar affinities to IGF2R proteins of human, canine and murine origin. We used naïve and synthetic antibody Fab-format phage display libraries to develop antibodies to a conserved region on IGF2R. The generated antibodies were radiolabeled and characterized in vitro and in vivo using human and canine OS patient-derived tumors in SCID mouse models. We demonstrate specific binding to IGF2R and tumor uptake in these models, as well as binding to tumor tissue of canine OS patients, making these antibodies suitable for further development of RIT for OS

Keen observational skills are essential for veterinarians; however, the development of these skills is not usually an explicit part of the veterinary curriculum. Fine arts–based (FAB) observation training has been shown to improve medical students’ observational skills and might also improve veterinary students’ observational skills. We compared FAB and pathology-based (PB) observation training in a veterinary cytology course. Students initially wrote a pre-test in which they described two cytology images and one art image, followed by participation in either FAB or PB observation training. Both groups completed a similar post-test immediately after training and a delayed post-test 4 weeks later following instruction in cytology. Differences between groups were noted only in the immediate post-test cytology descriptions. The PB group used significantly more specific vocabulary terms and significantly more accurate observations than the FAB group, suggesting an immediate benefit to the discipline-specific information gained in the PB observation training. In the delayed post-test, results for both groups were similar. The FAB group significantly increased their use of specific vocabulary terms and maintained but did not increase accurate observations following cytology instruction, while accurate observations decreased significantly for the PB group. The FAB group might have been able to generalize their observation skills to the discipline of cytology and to better retain these skills. Neither type of training resulted in both achievement and maintenance of the highest recorded scores for accurate observations. Both FAB and PB training led to improved observational skills, and explicit observation training may be useful for veterinary students.

One of the primary objectives of the Oncology Pathology Working Group (OPWG) is for oncologists and pathologists to collaboratively generate consensus documents to standardise aspects of and provide guidelines for oncologic pathology in veterinary species. Consensus is established through critical review of the peer‐reviewed literature relevant to a subgroup's particular focus. In this article, the authors provide a critical review of the current literature regarding methods for the diagnosis and classification of primary nodal lymphomas of dogs, including histopathology, cytopathology, immunophenotyping and assessment of molecular clonality. Knowledge gaps in the current literature and recommendations for future study are also reported. Major conclusions of this consensus include: (1) Histopathology with immunohistochemistry is required for complete diagnosis and classification of nodal lymphomas; (2) Immunohistochemistry and flow cytometry are the most reliable methods of immunophenotyping lymphomas, though neither is clearly superior to the other; (3) Molecular clonality testing should not be used in favour of immunophenotyping assays for classifying lymphomas; and (4) The use of emerging molecular tests for diagnosing lymphomas in the absence of histopathologic, cytopathologic, or immunophenotypic disease characterisation should be restricted to investigational settings until their diagnostic validity and the clinical benefit they confer to patients are more thoroughly characterised. This document represents the opinions of the OPWG and the authors; it does not constitute a formal endorsement by the American College of Veterinary Pathologists or the Veterinary Cancer Society.

Progress in prognostic factors, treatments, and outcome for both canine and human osteosarcoma (OS) has been minimal over the last three decades. Surface overexpression of the cation independent mannose-6-phosphate/insulin-like growth factor receptor type 2 (IGF2R) has been proven to occur in human OS cells. Subsequently, radioimmunotherapy (RIT) targeting IGF2R has demonstrated promising preliminary results. The main aims of this study were to investigate the expression of IGF2R in spontaneously occurring canine OS cells using immunohistochemistry (IHC) on archived biopsy samples and to assess its prognostic significance. Thirty-four dogs were included in the study. All cases showed that 80–100% of OS cells stained positive for IGF2R. IGF2R overexpression alone was not shown to have prognostic significance using both visual and quantitative methods of IHC staining intensity. This study has established for the first time the consistent expression of IGF2R in spontaneously occurring canine OS. This comparative oncology approach will allow further investigation into RIT as a novel treatment modality; first in canines and then in humans with OS. In addition, further studies should be performed to assess the true prognostic significance of IGF2R overexpression.