Abstract
791
Objectives: The most common amyloid disease that is not associated with the brain is light chain amyloidosis (AL). In the US there is estimated to be more than 4,000 new cases a year. Currently new immunotherapies are being developed and evaluated in clinical trials; however the lack of a good animal model has hampered development and made clinical translation more difficult. Our goal is to develop and validate new models of AL that can be used to study the targeting of amyloid-binding biological agents by using preclinical imaging. Here we report imaging studies of a new model of highly vascularized human AL amyloidoma model in mice. SPECT/CT imaging was used to evaluate localization of surgically-implanted human amyloid deposits.
Methods: To create the model, human amyloid extracts were purified from autopsy-derived, amyloid-laden tissues by using the standard water floatation method. Under protocol, the immunocompetent wild type mouse was surgically implanted with the extract either in the liver or in the spleen. After 5 days, the distribution of amyloid was assessed using an 125I-labeled amyloidophilic peptide tracer, p5+, by SPECT/CT imaging and microautoradiography.
Results: Amyloid injections in the liver were more successful than in the spleen and the deposits became highly vascularized focal lesions. Some of the amyloid material extruded from the site of injection and formed adhesions on other surrounding organ surfaces. The focal amyloid deposits in the liver were detected with 125I-p5+14 peptide.
Conclusion: Both SPECT/CT imaging and microautoradiography show that the surgical procedure can successfully be used to generate vascularized orthotopic human amyloid lesions within the mouse liver. This new model provides an example of a mouse with vascularized AL amyloid in an abdominal organ that can be used for validating the efficacy of novel imaging agents in vivo by the use of Preclinical SPECT/CT imaging.