In Vivo SPECT and Real-Time Gamma Camera Imaging of Biodistribution and Pharmacokinetics of siRNA Delivery Using an Optimized Radiolabeling and Purification Procedure

Single photon emission computed tomography (SPECT) imaging provides a three-dimensional method for exactly locating gamma emitters in a noninvasive procedure under in vivo conditions. For characterization of siRNA delivery systems, molecular imaging techniques are extremely helpful to follow biodist...

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Bibliographic Details
Published in:Bioconjugate chemistry 2009-01, Vol.20 (1), p.174-182
Main Authors: Merkel, Olivia M, Librizzi, Damiano, Pfestroff, Andreas, Schurrat, Tino, Béhé, Martin, Kissel, Thomas
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Gamma Cameras
Gamma rays
Isotope Labeling - methods
Mice
Mice, Inbred BALB C
Optimization
Pharmacokinetics
Pharmacology
Ribonucleic acid
RNA
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - pharmacokinetics
Scintillation Counting
Three dimensional imaging
Tissue Distribution
Tomography
Tomography, Emission-Computed, Single-Photon - methods
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Summary:Single photon emission computed tomography (SPECT) imaging provides a three-dimensional method for exactly locating gamma emitters in a noninvasive procedure under in vivo conditions. For characterization of siRNA delivery systems, molecular imaging techniques are extremely helpful to follow biodistribution under in experimental animal studies. Quantification of biodistribution of siRNA and nonviral delivery systems using this technique requires efficient methods to stably label siRNA with a gamma emitter (e.g., 111In or 99mTc) and to purify labeled material from excesses of radiolabel or linkers. In the following study, we have optimized labeling and purification of siRNA, which was then applied as free siRNA or after complexation with polyethylenimine (PEI) 25 kDa for in vivo real-time gamma camera and SPECT imaging. Quantification of scintillation counts in regions of interest (ROIs) was compared to conventional scintillation counting of dissected organs, and the data acquired by imaging was shown to corroborate that of scintillation counting. This optimization and proof of principle study demonstrates that biodistribution and pharmacokinetics of siRNA and the corresponding polyplexes can be determined using SPECT, leading to comparable results as conventional methodology.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc800408g