Quantitative Whole-Body Imaging of I-124-labeled Adeno-Associated Viral Vector Biodistribution in Nonhuman Primates. Academic Article uri icon

Overview

abstract

  • A method is presented for quantitative analysis of the biodistribution of adeno-associated virus (AAV) gene transfer vectors following in vivo administration. We used I-124 radiolabeling of the AAV capsid and positron emission tomography combined with compartmental modeling to quantify whole-body and organ-specific biodistribution of AAV capsids from 1 to 72 hr following administration. Using intravenous and intracisternal routes of administration of AAVrh.10 and AAV9 vectors to nonhuman primates in the absence or presence of anti-capsid immunity we have identified novel insights into initial capsid biodistribution and organ-specific capsid half-life. Neither I-124 labeled AAVrh.10 or AAV9 administered intravenously was detected at significant levels in the brain relative to the administered vector dose. Approximately 50% of the intravenously administered labeled capsids were dispersed throughout the body, independent of the liver, heart, and spleen. When administered by the intracisternal route, the labeled capsid had a half-life of approximately 10 hours in the cerebral spinal fluid (CSF), suggesting that by this route, the CSF serves as a source with slow diffusion into the brain. For both intravenous and intracisternal administration, there was significant influence of preexisting anti-capsid immunity on I-124-capsid biodistribution. The methodology facilitates quantitative in vivo viral vector dosimetry, which can serve as a technique for evaluation of both on and off-target organ biodistribution, and potentially accelerate gene therapy development through rapid prototyping of novel vector designs.

publication date

  • November 24, 2020

Identity

Digital Object Identifier (DOI)

  • 10.1089/hum.2020.116

PubMed ID

  • 33233962