Evidence map›Paper›PMID 25655631›Full record

ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2015

Cerenkov-specific contrast agents for detection of pH in vivo.

Julie Czupryna, Alexander V Kachur, Eric Blankemeyer, Anatoliy V Popov, Alejandro D Arroyo, Joel S Karp, Edward J Delikatny

Open access · bronzeAbstract read
In one paragraph

Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

12 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Observational
  3. Review
  4. Article
  5. Article
  6. Article
  7. Cerenkov-Activated Sticky Tag for In Vivo Fluorescence Imaging.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2018
    Article
  8. Review
  9. Article
  10. Molecular Imaging in Nanotechnology and Theranostics.Molecular imaging and biology · 2017
    Review
  11. Article
  12. Article
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

7 authors at 1 institution in 1 country.

Julie CzuprynaSmall Animal Imaging Facility, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Alexander V KachurSmall Animal Imaging Facility, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Eric BlankemeyerSmall Animal Imaging Facility, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Anatoliy V PopovSmall Animal Imaging Facility, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Alejandro D ArroyoSmall Animal Imaging Facility, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Joel S KarpSmall Animal Imaging Facility, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Edward J DelikatnySmall Animal Imaging Facility, Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania delikatn@mail.med.upenn.edu.
University of Pennsylvania · US

Funding

INSTITUTIONAL CLINICAL AND TRANSLATIONAL SCIENCE AWARDUL1RR024134 · NCRR · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2006 to 2011
$70.4M
Institutional Clinical and Translational Science AwardUL1TR000003 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2012 to 2015
$38.9M
PREDOCTORAL TRAINING PROGRAM IN PHARMACOLOGYT32GM008076 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BLENDY, JULIE A · 1985 to 2023
$10.8M
Cerenkov Specific Contrast AgentsR01EB018645 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI DELIKATNY, EDWARD J · 2014 to 2017
$1.4M
NCATS NIH HHS UL1 TR000003NCRR NIH HHS UL1 RR024134NCRR NIH HHS UL 1RR024134NIBIB NIH HHS R01 EB018645NIBIB NIH HHS R01 EB018645-01NIGMS NIH HHS T32 GM008076
6 · The paper itself

Abstract

unlabelledWe report the design, testing, and in vivo application of pH-sensitive contrast agents designed specifically for Cerenkov imaging. Radioisotopes used for PET emit photons via Cerenkov radiation. The multispectral emission of Cerenkov radiation allows for selective bandwidth quenching, in which a band of photons is quenched by absorption by a functional dye. Under acidic conditions, (18)F-labeled derivatives emit the full spectrum of Cerenkov light. Under basic conditions, the dyes change color and a wavelength-dependent quenching of Cerenkov emission is observed.

methodsMono- and di-(18)F-labeled derivatives of phenolsulfonphthalein (phenol red) and meta-cresolsulfonphthalein (cresol purple) were synthesized by electrophilic fluorination. Cerenkov emission was measured at different wavelengths as a function of pH in vitro. Intramolecular response was measured in fluorinated probes and intermolecular quenching by mixing phenolphthalein with (18)F-FDG. Monofluorocresol purple (MFCP) was tested in mice treated with acetazolamide to cause urinary alkalinization, and Cerenkov images were compared with PET images.

resultsFluorinated pH indicators were produced with radiochemical yields of 4%-11% at greater than 90% purity. Selective Cerenkov quenching was observed intramolecularly with difluorophenol red or monofluorocresol purple and intermolecularly in phenolphthalein (18)F-FDG mixtures. The probes were selectively quenched in the bandwidth closest to the indicator's absorption maximum (λmax) at pHs above the indicator pKa (the negative logarithm of the acid dissociation constant). Addition of acid or base to the probes resulted in reversible switching from unquenched to quenched emission. In vivo, the bladders of acetazolamide-treated mice exhibited a wavelength-dependent quenching in Cerenkov emission, with the greatest reduction occurring near the λmax. Ratiometric imaging at 2 wavelengths showed significant decreases in Cerenkov emission at basic pH and allowed the estimation of absolute pH in vivo.

conclusionWe have created contrast agents that selectively quench photons emitted during Cerenkov radiation within a given bandwidth. In the presence of a functional dye, such as a pH indicator, this selective quenching allows for a functional determination of pH in vitro and in vivo. This method can be used to obtain functional information from radiolabeled probes using multimodal imaging. This approach allows for the imaging of nonfluorescent chromophores and is generalizable to any functional dye that absorbs at suitable wavelengths.

Indexed as

AcetazolamideAnimalsContrast MediaDisease Models, AnimalFluorine RadioisotopesFluorodeoxyglucose F18Hydrogen-Ion ConcentrationMiceModels, ChemicalMultimodal ImagingOptics and PhotonicsPhenolphthaleinPhenolsulfonphthaleinPhotonsPositron-Emission TomographyRadioisotopesAcetazolamideContrast MediaFluorine RadioisotopesFluorodeoxyglucose F18monofluorocresol purplePhenolphthaleinPhenolsulfonphthaleinRadioisotopesRadiopharmaceuticalsCerenkov imagingelectrophilic fluorinationmetacresol purplephenolphthaleinpH measurementratiometric imaging

Identifiers

PMID25655631
PMCPMC4543314
OpenAlexW2165993894

What OpenQuestion holds

Textmetadata
LicenceTDM
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.