Chao Wang1, Benjamin I Leach1, Deanne Lister1, Stephen R Adams2, Hongyan Xu1, Carl Hoh1, Patrick McConville1,3, Jing Zhang4, Karen Messer4, Eric T Ahrens5. 1. Department of Radiology, University of California San Diego, La Jolla, California. 2. Department of Pharmacology, University of California San Diego, La Jolla, California. 3. Invicro, Inc., Boston, Massachusetts; and. 4. Moores Cancer Center, University of California San Diego, La Jolla, California. 5. Department of Radiology, University of California San Diego, La Jolla, California; eta@ucsd.edu.
Abstract
Inflammation is associated with a range of serious human conditions, including autoimmune and cardiovascular diseases and cancer. The ability to image active inflammatory processes greatly enhances our ability to diagnose and treat these diseases at an early stage. We describe molecular compositions enabling sensitive and precise imaging of inflammatory hotspots in vivo. Methods: A functionalized nanoemulsion with a fluorocarbon-encapsulated radiometal chelate (FERM) was developed to serve as a platform for multimodal imaging probe development. The 19F-containing FERM nanoemulsion encapsulates 89Zr in the fluorous oil via a fluorinated hydroxamic acid chelate. Simple mixing of the radiometal with the preformed aqueous nanoemulsion before use yields FERM, a stable in vivo cell tracer, enabling whole-body 89Zr PET and 19F MRI after a single intravenous injection. Results: The FERM nanoemulsion was intrinsically taken up by phagocytic immune cells, particularly macrophages, with high specificity. FERM stability was demonstrated by a high correlation between the 19F and 89Zr content in the blood (correlation coefficient > 0.99). Image sensitivity at a low dose (37 kBq) was observed in a rodent model of acute infection. The versatility of FERM was further demonstrated in models of inflammatory bowel disease and 4T1 tumor. Conclusion: Multimodal detection using FERM yields robust whole-body lesion detection and leverages the strengths of combined PET and 19F MRI. The FERM nanoemulsion has scalable production and is potentially useful for precise diagnosis, stratification, and treatment monitoring of inflammatory diseases.
Inflammation is associated with a range of serious human conditions, including autoimmune and cardiovascular diseases and cancer. The ability to image active inflammatory processes greatly enhances our ability to diagnose and treat these diseases at an early stage. We describe molecular compositions enabling sensitive and precise imaging of inflammatory hotspots in vivo. Methods: A functionalized nanoemulsion with a fluorocarbon-encapsulated radiometal chelate (FERM) was developed to serve as a platform for multimodal imaging probe development. The 19F-containing FERM nanoemulsion encapsulates 89Zr in the fluorous oil via a fluorinated hydroxamic acid chelate. Simple mixing of the radiometal with the preformed aqueous nanoemulsion before use yields FERM, a stable in vivo cell tracer, enabling whole-body 89Zr PET and 19F MRI after a single intravenous injection. Results: The FERM nanoemulsion was intrinsically taken up by phagocytic immune cells, particularly macrophages, with high specificity. FERM stability was demonstrated by a high correlation between the 19F and 89Zr content in the blood (correlation coefficient > 0.99). Image sensitivity at a low dose (37 kBq) was observed in a rodent model of acute infection. The versatility of FERM was further demonstrated in models of inflammatory bowel disease and 4T1 tumor. Conclusion: Multimodal detection using FERM yields robust whole-body lesion detection and leverages the strengths of combined PET and 19F MRI. The FERM nanoemulsion has scalable production and is potentially useful for precise diagnosis, stratification, and treatment monitoring of inflammatory diseases.
Authors: Aman Khurana; Fanny Chapelin; Hongyan Xu; Joseph R Acevedo; Alfred Molinolo; Quyen Nguyen; Eric T Ahrens Journal: Magn Reson Med Date: 2017-07-26 Impact factor: 4.668
Authors: Anthony Balducci; Yi Wen; Yang Zhang; Brooke M Helfer; T Kevin Hitchens; Wilson S Meng; Amy K Wesa; Jelena M Janjic Journal: Oncoimmunology Date: 2013-02-01 Impact factor: 8.110
Authors: Yvonne W S Jauw; C Willemien Menke-van der Houven van Oordt; Otto S Hoekstra; N Harry Hendrikse; Danielle J Vugts; Josée M Zijlstra; Marc C Huisman; Guus A M S van Dongen Journal: Front Pharmacol Date: 2016-05-24 Impact factor: 5.810
Authors: Sandra Díez-Villares; Juan Pellico; Noemí Gómez-Lado; Santiago Grijalvo; Sandra Alijas; Ramon Eritja; Fernando Herranz; Pablo Aguiar; María de la Fuente Journal: Int J Nanomedicine Date: 2021-08-26