RESUMEN

Magnetic resonance imaging is the gold standard for diagnosing intervertebral disc (IVD) degeneration in dogs. However, published methods for quantifying severity or progression of IVD degeneration are currently limited. Mapping MRI sequences are used in humans for quantifying IVD degeneration but have rarely been applied in dogs. The objective of this prospective, method comparison study was to evaluate variable flip angle T1 mapping and multiecho T2 and T2* mapping as methods for quantifying canine lumbar IVD degeneration in twenty canine patients without clinical signs of spinal disease. Ventral and dorsal lumbar IVD widths were measured on radiographs, and lumbar IVDs were assigned a qualitative Pfirrmann grade based on standard T2-weighted sequences. T1, T2, and T2* relaxation times of the nucleus pulposus (NP) were measured on corresponding maps using manual-drawn ROIs. Strong intra- and interrater agreements were found (P < 0.01) for NP relaxation times. Radiographic IVD widths and T1, T2, and T2* mapping NP relaxation times were negatively correlated with Pfirrmann grading (P < 0.01). Significant differences in T1 NP relaxation times were found between Pfirrmann grade I and the other grades (P < 0.01). Significant differences in T2 and T2* NP relaxation times were found between grade I and the other grades and between grades II and III (P < 0.01). Findings indicated that T1, T2, and T2* MRI mapping sequences are feasible in dogs. Measured NP relaxation times were repeatable and decreased when Pfirrmann grades increased. These methods may be useful for quantifying the effects of regenerative treatment interventions in future longitudinal studies.

Asunto(s)

Enfermedades de los Perros , Degeneración del Disco Intervertebral , Disco Intervertebral , Humanos , Perros , Animales , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/veterinaria , Estudios Prospectivos , Imagen por Resonancia Magnética/veterinaria , Imagen por Resonancia Magnética/métodos , Región Lumbosacra , Interpretación de Imagen Asistida por Computador , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/patología , Disco Intervertebral/diagnóstico por imagen , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/patología

RESUMEN

Antibodies directed against CD22 have been used in radioimmunotherapy (RIT) clinical trials to treat patients with diffuse large B-cell lymphoma (DLBCL) with promising results. However, relevant preclinical models are needed to facilitate the evaluation and optimization of new protocols. Spontaneous DLBCL in dogs is a tumor model that may help accelerate the development of new methodologies and therapeutic strategies for RIT targeting CD22. Seven murine monoclonal antibodies specific for canine CD22 were produced by the hybridoma method and characterized. The antibodies' affinity and epitopic maps, their internalization capability and usefulness for diagnosis in immunohistochemistry were determined. Biodistribution and PET imaging on a mouse xenogeneic model of dog DLBCL was used to choose the most promising antibody for our purposes. PET-CT results confirmed biodistribution study observations and allowed tumor localization. The selected antibody, 10C6, was successfully used on a dog with spontaneous DLBCL for SPECT-CT imaging in the context of disease staging, validating its efficacy for diagnosis and the feasibility of future RIT assays. This first attempt at phenotypic imaging on dogs paves the way to implementing quantitative imaging methodologies that would be transposable to humans in a theranostic approach. Taking into account the feedback of existing human radioimmunotherapy clinical trials targeting CD22, animal trials are planned to investigate protocol improvements that are difficult to consider in humans due to ethical concerns.