Bioluminescence Applications in Preclinical Oncology Research

Kalra, Jessica; Bally, Marcel B.

doi:10.5772/36736

Cited by 2 publications

(2 citation statements)

References 106 publications

(69 reference statements)

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“…The phenomenon of bioluminescence stays in the spotlight of researchers in a wide range of fields of science, including fundamental and applied biology, chemistry, and medicine. Due to the recent advances in light detection technologies, high quantum yields of bioluminescence and relative nontoxicity of luciferin reactions, a tremendous range of analytical techniques based on this phenomenon have been developed, most of which are now actively used in cancer studies, investigations of infectious diseases, − and environmental monitoring. , Luciferases are extensively used as convenient instruments in ATP tests, reporter gene analysis, biosensors, ,, in BRET pairs (bioluminescent resonance energy transfer) − and luciferase complementation assay − for protein–protein and cell–cell interaction studies and for bioimaging in vivo of tumors, , bacterial and other infections (malaria, fungi), and so forth. , …”

Section: Modern Applications Of Bioluminescencementioning

confidence: 99%

A Tale Of Two Luciferins: Fungal and Earthworm New Bioluminescent Systems

2016

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Bioluminescence, the ability of a living organism to produce light through a chemical reaction, is one of Nature's most amazing phenomena widely spread among marine and terrestrial species. There are various different mechanisms underlying the emission of "cold light", but all involve a small molecule, luciferin, that provides energy for light-generation upon oxidation, and a protein, luciferase, that catalyzes the reaction. Different species often use different proteins and substrates in the process, which suggests that the ability to produce light evolved independently several times throughout evolution. Currently, it is estimated that there are more than 30 different mechanisms of bioluminescence. Even though the chemical foundation underlying the bioluminescence phenomenon is by now generally understood, only a handful of luciferins have been isolated and characterized. Today, the known bioluminescence reactions are used as indispensable analytical tools in various fields of science and technology. A pressing need for new bioluminescent analytical techniques with a wider range of practical applications stimulates the search and chemical studies of new bioluminescent systems. In the past few years two such systems were unraveled: those of the earthworms Fridericia heliota and the higher fungi. The luciferins of these two systems do not share structural similarity with the previously known ones. This Account will survey structure elucidation of the novel luciferins and identification of their mechanisms of action. Fridericia luciferin is a key component of a novel ATP-dependent bioluminescence system. Structural studies were performed on 0.005 mg of natural substance and revealed its unusual extensively modified peptidic nature. Elucidation of Fridericia oxyluciferin revealed that oxidative decarboxylation of a lysine fragment of luciferin supplies energy for light generation, while a fluorescent CompX moiety remains intact and serves as a light emitter. Along with luciferin, a number of its natural analogs were found in the extracts of worm biomass. They occurred to be highly unusual modified peptides comprising a set of amino acids, including threonine, aminobutyric acid, homoarginine, unsymmetrical N,N-dimethylarginine and extensively modified tyrosine. These natural compounds represent a unique peptide chemistry found in terrestrial animals and raise novel questions concerning their biosynthetic origin. Also in this Account we discuss identification of the luciferin of higher fungi 3-hydroxyhispidin which is biosynthesized by oxidation of the precursor hispidin, a known fungal and plant secondary metabolite. Furthermore, it was shown that 3-hydroxyhispidin leads to bioluminescence in extracts from four diverse genera of luminous fungi, thus suggesting a common biochemical mechanism for fungal bioluminescence.

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Section: Modern Applications Of Bioluminescencementioning

confidence: 99%

A Tale Of Two Luciferins: Fungal and Earthworm New Bioluminescent Systems

2016

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“…Thus, the development of accurate 3D bioluminescence tomography (BLT) reconstruction algorithms can open new doors for pre-clinical image-guided radiotherapy. In addition, BLT allows targeting selective regions inside tumors with ionizing radiation, investigating the tumor response to treatment, and many other research opportunities (O'Neill et al 2010, Kalra and Bally 2012). However, due to the limitations of the BLIbased targeting, a sub-millimeter targeting accuracy is considered satisfactory but there are no available guidelines or consensus about it.…”

Section: Introductionmentioning

confidence: 99%

A deep learning and Monte Carlo based framework for bioluminescence imaging center of mass-guided glioblastoma targeting

et al. 2022

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Objective: Bioluminescence imaging (BLI) is a valuable tool for non-invasive monitoring of glioblastoma multiforme (GBM) tumor-bearing small animals without incurring x-ray radiation burden. However, the use of this imaging modality is limited due to photon scattering and lack of spatial information. Attempts at reconstructing bioluminescence tomography (BLT) using mathematical models of light propagation show limited progress. Approach: This paper employed a different approach by using a deep convolutional neural network (CNN) to predict the tumor's center of mass (CoM). Transfer-learning with a sizeable artificial database is employed to facilitate the training process for, the much smaller, target database including Monte Carlo (MC) simulations of real orthotopic glioblastoma models. Predicted CoM was then used to estimate a BLI-based planning target volume (bPTV), by using the CoM as the center of a sphere, encompassing the tumor. The volume of the encompassing target sphere was estimated based on the total number of photons reaching the skin surface. Main Results: Results show sub-millimeter accuracy for CoM prediction with a median error of 0.59 mm. The proposed method also provides promising performance for BLI-based tumor targeting with on average 94% of the tumor inside the bPTV while keeping the average healthy tissue coverage below 10%. Significance: This work introduced a framework for developing and using a CNN for targeted radiation studies for GBM based on BLI. The framework will enable biologists to use BLI as their main image-guidance tool to target GBM tumors in rat models, avoiding delivery of high x-ray imaging dose to the animals.

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Bioluminescence Applications in Preclinical Oncology Research

Cited by 2 publications

References 106 publications

A Tale Of Two Luciferins: Fungal and Earthworm New Bioluminescent Systems

A Tale Of Two Luciferins: Fungal and Earthworm New Bioluminescent Systems

A deep learning and Monte Carlo based framework for bioluminescence imaging center of mass-guided glioblastoma targeting

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