Luciferin Derivatives for Enhanced in Vitro and in Vivo Bioluminescence Assays.
From: Department of Pediatrics, Radiology, and Microbiology and Immunology, Stanford University, Clark Center, 318 Campus Drive, Stanford, California 94305, USA.
Biochemistry
- Publish Date: Sep 2006
- ISSN: 0006-2960
- Volume: 45
- Issue: 37
- Pages: 11103-12
- Medium: Print
- Language: English
- Citation (JAMA): Shinde Rajesh, Perkins Julie, Contag Christopher H, et al. Luciferin Derivatives for Enhanced in Vitro and in Vivo Bioluminescence Assays.. Biochemistry Sep 2006;45:11103-12
Abstract
In vivo bioluminescence imaging has become a cornerstone technology for preclinical molecular imaging. This imaging method is based on light-emitting enzymes, luciferases, which require specific substrates for light production. When linked to a specific biological process in an animal model of human biology or disease, the enzyme-substrate interactions become biological indicators that can be studied noninvasively in living animals. Signal intensity in these animal models depends on the availability of the substrate for the reaction within living cells in intact organs. The biodistribution and clearance rates of the substrates are therefore directly related to optimal imaging times and signal intensities and ultimately determine the sensitivity of detection and predictability of the model. Modifications of d-luciferin, the substrate for the luciferases obtained from beetle, including fireflies, result in novel properties and offer opportunities for improved bioassays. For this purpose, we have synthesized a conjugate, glycine-d-aminoluciferin, and investigated its properties relative to those of d-aminoluciferin and d-luciferin. The three substrates exhibited different kinetic properties and different intracellular accumulation profiles due to differences in their molecular structure, which in turn influenced their biodistribution in animals. Glycine-d-aminoluciferin had a longer in vivo circulation time than the other two substrates. The ability to assay luciferase in vitro and in vivo using these substrates, which exhibit different pharmacokinetic and pharmacodynamic properties, will provide flexibility and improve current imaging capabilities.
Mesh Headings (Keywords): Animals, Firefly Luciferin, Luminescent Agents, Luminescent Measurements, Mice, Mice, Transgenic, Molecular Structure
Check for Full Text / PubMed Unique Identifier (PMID): 16964971
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