Evidence map›Paper›PMID 34887255›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2022

Factors Influencing Luciferase-Based Bioluminescent Imaging in Preclinical Models of Brain Tumor.

Minjee Kim, Shiv K Gupta, Wenjuan Zhang, Surabhi Talele, Afroz S Mohammad, Janice Laramy, Ann C Mladek, Shuangling Zhang, Jann N Sarkaria, William F Elmquist

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 10 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Minjee KimBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., W.Z., S.T., A.S.M., J.L., S.Z., W.F.E.) and Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (S.K.G., A.C.M., J.N.S.).
Shiv K GuptaBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., W.Z., S.T., A.S.M., J.L., S.Z., W.F.E.) and Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (S.K.G., A.C.M., J.N.S.).
Wenjuan ZhangBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., W.Z., S.T., A.S.M., J.L., S.Z., W.F.E.) and Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (S.K.G., A.C.M., J.N.S.).
Surabhi TaleleBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., W.Z., S.T., A.S.M., J.L., S.Z., W.F.E.) and Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (S.K.G., A.C.M., J.N.S.).
Afroz S MohammadBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., W.Z., S.T., A.S.M., J.L., S.Z., W.F.E.) and Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (S.K.G., A.C.M., J.N.S.).
Janice LaramyBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., W.Z., S.T., A.S.M., J.L., S.Z., W.F.E.) and Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (S.K.G., A.C.M., J.N.S.).
Ann C MladekBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., W.Z., S.T., A.S.M., J.L., S.Z., W.F.E.) and Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (S.K.G., A.C.M., J.N.S.).
Shuangling ZhangBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., W.Z., S.T., A.S.M., J.L., S.Z., W.F.E.) and Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (S.K.G., A.C.M., J.N.S.).
Jann N SarkariaBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., W.Z., S.T., A.S.M., J.L., S.Z., W.F.E.) and Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (S.K.G., A.C.M., J.N.S.).
William F ElmquistBrain Barriers Research Center, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (M.K., W.Z., S.T., A.S.M., J.L., S.Z., W.F.E.) and Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (S.K.G., A.C.M., J.N.S.) elmqu011@umn.edu.
University of Minnesota · USMayo Clinic · US

Funding

Transport Oncophysics CoreU54CA210181 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI SHEN, HAIFA · 2016 to 2020
$9.3M
Pre-Clinical Novel Radiosensitizer Evaluation Program for Brain TumorsU01CA227954 · NCI · MAYO CLINIC ROCHESTER · PI SARKARIA, JANN N. · 2018 to 2022
$3.0M
Influence of Anti-Angiogenic Therapy on Drug Delivery to Brain TumorsR01NS077921 · NINDS · UNIVERSITY OF MINNESOTA · PI ELMQUIST, WILLIAM, SARKARIA, JANN N. · 2012 to 2016
$2.5M
Improving Delivery of Molecularly-Targeted Therapy to Invasive Glioma CellsR01CA138437 · NCI · UNIVERSITY OF MINNESOTA · PI ELMQUIST, WILLIAM, OHLFEST, JOHN R · 2010 to 2014
$1.5M
NCI NIH HHS R01 CA138437NCI NIH HHS U01 CA227954NCI NIH HHS U54 CA210181NINDS NIH HHS R01 NS077921
6 · The paper itself

Abstract

Bioluminescent imaging (BLI) is a powerful tool in biomedical research to measure gene expression and tumor growth. The current study examined factors that influence the BLI signal, specifically focusing on the tissue distribution of two luciferase substrates, D-luciferin and CycLuc1. D-luciferin, a natural substrate of firefly luciferase, has been reported to have limited brain distribution, possibly due to the efflux transporter, breast cancer resistance protein (Bcrp), at the blood-brain barrier. CycLuc1, a synthetic analog of D-luciferin, has a greater BLI signal at lower doses than D-luciferin, especially in the brain. Our results indicate that limited brain distribution of D-luciferin and CycLuc1 is predominantly dictated by their low intrinsic permeability across the cell membrane, where the efflux transporter, Bcrp, plays a relatively minor role. Both genetic ablation and pharmacological inhibition of Bcrp decreased the systemic clearance of both luciferase substrates, significantly increasing exposure in the blood and, hence, in organs and tissues. These data also indicate that the biodistribution of luciferase substrates can be differentially influenced in luciferase-bearing tissues, leading to a "tissue-dependent" BLI signal. The results of this study point to the need to consider multiple mechanisms that influence the distribution of luciferase substrates. SIGNIFICANCE STATEMENT: Bioluminescence is used to monitor many biological processes, including tumor growth. This study examined the pharmacokinetics, brain distribution, and the role of active efflux transporters on the luciferase substrates D-luciferin and CycLuc1. CycLuc1 has a more sustained systemic circulation time (longer half-life) that can provide an advantage for the superior imaging outcome of CycLuc1 over D-luciferin. The disparity in imaging intensities between brain and peripheral sites is due to low intrinsic permeability of these luciferase substrates across the blood-brain barrier.

Indexed as

Brain NeoplasmsLuminescent MeasurementsATP Binding Cassette Transporter, Subfamily G, Member 2HumansLuciferasesLuciferases, FireflyNeoplasm ProteinsTissue DistributionATP Binding Cassette Transporter, Subfamily G, Member 2LuciferasesLuciferases, FireflyNeoplasm Proteins

Identifiers

PMID34887255
PMCPMC8969130
OpenAlexW4200342761

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.