Imaging and tissue biodistribution of 99mTc-labeled adenovirus knob (serotype 5)

K. R. Zinn, J. T. Douglas, C. A. Smyth, H. G. Liu, Q. Wu, V. N. Krasnykh, J. D. Mountz, D. T. Curiel, J. M. Mountz

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Hepatic sequestration of systemically administered adenoviral vectors reduces the number of viral particles available for delivery to other tissues. The biological basis of this phenomenon was investigated using a new in vivo technique which permitted imaging in real time. Recombinant adenovirus serotype 5 knob (Ad5K) was radiolabeled with the gamma-emitter 99mTc (half-life = 6 h). Scatchard analysis of the 99mTc-Ad5K showed specific, high-affinity binding to U293 cells (K(d)= 1.4 ± 0.5 nM), demonstrating that the radiolabeling process had no effect on receptor. In vivo dynamic imaging with an Anger gamma camera revealed that the liver binding followed an exponential rise to maximum, with a measured 100% extraction efficiency. Initially, the liver binding capacity was 3.1 ± 0.4 μg Ad5K, equivalent to approximately 17,000 Ad5K molecules per liver cell. Liver binding was blocked by preincubation of Ad5K with neutralizing anti-Ad5K antibody; a 50% reduction in liver uptake was demonstrated by imaging. Unlabeled Ad5K was more effective in blocking liver uptake of 99mTc-Ad5K, whereas irrelevant unlabeled Ad3K had no effect. Imaging data for the liver uptake studies were in agreement with biodistribution determined by removing and measuring tissues. These data demonstrated that in vivo imaging is a sensitive tool for measuring changes to liver tropism. Similar imaging techniques can be applied to adenovirus vectors to measure specific targeting for gene therapy.

Original languageEnglish
Pages (from-to)798-808
Number of pages11
JournalGene therapy
Volume5
Issue number6
DOIs
StatePublished - 1998

Keywords

  • Adenovirus knob
  • Imaging
  • Tc

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