Application of stimulated Raman scattering for measurement of intracellular drug distribution

 (Conference Presentation)

Valerie Brunton; William Tipping; Kristel Sepp; Martin Lee; Alison Hulme

doi:10.1117/12.2511244

4 March 2019 Application of stimulated Raman scattering for measurement of intracellular drug distribution (Conference Presentation)

Valerie Brunton, William Tipping, Kristel Sepp, Martin Lee, Alison Hulme

Author Affiliations +

Proceedings Volume 10859, Visualizing and Quantifying Drug Distribution in Tissue III; 108590E (2019) https://doi.org/10.1117/12.2511244
Event: SPIE BiOS, 2019, San Francisco, California, United States

Abstract

Oncology drug development is costly and ineffective with a 5% success rate from first-in-man studies to new drug registration. A task force set up to address issues in anticancer therapy development highlighted the necessity to demonstrate proof of mechanism and obtain information on key pharmacokinetic aspects of drug behaviour in both preclinical and early clinical trials. Spectroscopically bioorthogonal Raman detection in the “cellular-silent’ region presents an optimal region for drug imaging, as there is minimal contribution from endogenous cellular biomolecules thus improving detection sensitivity. This offer the potential to transform our understanding of intracellular drug distribution and mechanism of action. We demonstrate the utility of stimulated Raman scattering (SRS) in mapping intracellular concentrations of the tyrosine kinase inhibitor ponatinib used in the treatment of chronic myeloid leukemia and link this to resistance mechanisms associated with ponatinib treatment. As few drugs have inherent Raman active groups (5% of FDA approved drugs) further adoption and widespread use of SRS will require addition of bioorthogonal tags in the majority of cases. We have established an effective workflow for the design and use of Raman-labels for intracellular imaging. An iterative strategy of Raman-label design and validation identified minimally perturbative bis(alkyne) labels with approximately 60-fold increase in Raman scattering activity, compared to the mono-alkynes previously used. Combining SRS microscopy with this biorthogonal Raman labelling approach enabled direct visualisation of drug uptake to be correlated with markers of cell cycle status, and mapped across intracellular structures using multi-modal imaging platforms.

Conference Presentation

Citation Download Citation

Valerie Brunton, William Tipping, Kristel Sepp, Martin Lee, and Alison Hulme "Application of stimulated Raman scattering for measurement of intracellular drug distribution (Conference Presentation)", Proc. SPIE 10859, Visualizing and Quantifying Drug Distribution in Tissue III, 108590E (4 March 2019); https://doi.org/10.1117/12.2511244

ACCESS THE FULL ARTICLE

INSTITUTIONAL
Select your institution to access the SPIE Digital Library.

SELECT YOUR INSTITUTION

PERSONAL
Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.

PERSONAL SIGN IN

No SPIE Account? Create one

PURCHASE THIS CONTENT

SUBSCRIBE TO DIGITAL LIBRARY

50 downloads per 1-year subscription

Members: $195

Non-members: $335 ADD TO CART

25 downloads per 1 - year subscription

Members: $145

Non-members: $250 ADD TO CART

PURCHASE SINGLE ARTICLE

Includes PDF, HTML & Video, when available

Members: $17.00

Non-members: $21.00 ADD TO CART

PROCEEDINGS
PRESENTATION

WATCH
PRESENTATION SAVE TO MY LIBRARY

GET CITATION

KEYWORDS

Raman scattering

Raman spectroscopy

Scatter measurement

Clinical trials

Drug development

Leukemia

Microscopy

Show All Keywords

Keywords/Phrases

Search In:

Publication Years