title: Radioiodinated Capsids Facilitate In Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors.
abstract: Viral vector mediated gene therapy has become commonplace in clinical trials for a wide range of inherited disorders. Successful gene transfer depends on a number of factors, of which tissue tropism is among the most important. To date, definitive mapping of the spatial and temporal distribution of viral vectors in vivo has generally required postmortem examination of tissue. Here we present two methods for radiolabeling adeno-associated virus (AAV), one of the most commonly used viral vectors for gene therapy trials, and demonstrate their potential usefulness in the development of surrogate markers for vector delivery during the first week after administration. Specifically, we labeled adeno-associated virus serotype 10 expressing the coding sequences for the CLN2 gene implicated in late infantile neuronal ceroid lipofuscinosis with iodine-124. Using direct (Iodogen) and indirect (modified Bolton-Hunter) methods, we observed the vector in the murine brain for up to one week using positron emission tomography. Capsid radioiodination of viral vectors enables non-invasive, whole body, in vivo evaluation of spatial and temporal vector distribution that should inform methods for efficacious gene therapy over a broad range of applications.
authors.affiliation: Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kothari
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
authors.forename: B P
authors.initials: BP
authors.lastname: De
authors.affiliation: Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: B
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Chiuchiolo
authors.affiliation: Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: D
authors.initials: D
authors.lastname: Kim
authors.affiliation: Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: A
authors.initials: A
authors.lastname: Nikolopoulou
authors.affiliation: Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: A
authors.initials: A
authors.lastname: Amor-Coarasa
authors.affiliation: Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Dyke
authors.affiliation: Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: H U
authors.initials: HU
authors.lastname: Voss
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Kaminsky
authors.affiliation: Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: C P
authors.initials: CP
authors.lastname: Foley
authors.affiliation: Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Vallabhajosula
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: B
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: DiMagno
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sondhi
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Crystal
authors.affiliation: Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Babich
authors.affiliation: Citigroup Biomedical Imaging Center, Department of Radiology, Weill Cornell Medical College, New York, New York, USA.|Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
authors.forename: D
authors.initials: D
authors.lastname: Ballon
mesh_terms: D000626:Aminopeptidases / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging*; D036022:Capsid Proteins / Q000032:analysis* / Q000528:radiation effects; D000229:Dependovirus / Q000235:genetics*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000032:analysis*; D006801:Humans; D007457:Iodine Radioisotopes / Q000008:administration & dosage*; D008297:Male; D049268:Positron-Emission Tomography; D011877:Radionuclide Imaging / Q000379:methods*; D057057:Serine Proteases / Q000378:metabolism; D000091346:Tripeptidyl-Peptidase 1; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D036022:Capsid Proteins; D007457:Iodine Radioisotopes; D000091346:Tripeptidyl-Peptidase 1; C012385:1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycoluril; D014508:Urea; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C000717267:TPP1 protein, human