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Photoacoustic imaging of cancer treatment response: Early detection of therapeutic effect from thermosensitive liposomes

Photoacoustic imaging of cancer treatment response: Early detection of therapeutic effect from thermosensitive liposomes
Photoacoustic imaging of cancer treatment response: Early detection of therapeutic effect from thermosensitive liposomes

Imaging methods capable of indicating the potential for success of an individualized treatment course, during or immediately following the treatment, could improve therapeutic outcomes. Temperature Sensitive Liposomes (TSLs) provide an effective way to deliver chemotherapeutics to a localized tumoral area heated to mild-hyperthermia (HT). The high drug levels reached in the tumor vasculature lead to increased tumor regression via the cascade of events during and immediately following treatment. For a TSL carrying doxorubicin (DOX) these include the rapid and intense exposure of endothelial cells to high drug concentrations, hemorrhage, blood coagulation and vascular shutdown. In this study, ultrasound-guided photoacoustic imaging was used to probe the changes to tumors following treatment with the TSL, HaT-DOX (Heat activated cytoToxic). Levels of oxygen saturation (sO2) were studied in a longitudinal manner, from 30 min pre-treatment to 7 days post-treatment. The efficacious treatments of HT-HaT-DOX were shown to induce a significant drop in sO2 (>10%) as early as 30 min post-treatment that led to tumor regression (in 90% of cases); HT-Saline and non-efficacious HT-HaT-DOX (10% of cases) treatments did not show any significant change in sO2 at these timepoints. The changes in sO2 were further corroborated with histological data, using the vascular and perfusion markers CD31 and FITC-lectin. These results allowed us to further surmise a plausible mechanism of the cellular events taking place in the TSL treated tumor regions over the first 24 hours post-treatment. The potential for using photoacoustic imaging to measure tumor sO2 as a surrogate prognostic marker for predicting therapeutic outcome with a TSL treatment is demonstrated.

1932-6203
May, Jonathan P.
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Hysi, Eno
930da6bf-baf4-4334-8cc8-ee0264476b32
Wirtzfeld, Lauren A.
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Undzys, Elijus
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Li, Shyh Dar
9a960896-36e7-4eb8-bd39-55580c60e36d
Kolios, Michael C.
524bd088-1670-4d3c-9817-5298a4b1eebd
May, Jonathan P.
b54a262b-9f32-4435-8866-3b9c495294f3
Hysi, Eno
930da6bf-baf4-4334-8cc8-ee0264476b32
Wirtzfeld, Lauren A.
e46c0f07-84dc-4439-b349-36f81c49c413
Undzys, Elijus
226e7879-8bef-4715-9e72-d405e59d6dcb
Li, Shyh Dar
9a960896-36e7-4eb8-bd39-55580c60e36d
Kolios, Michael C.
524bd088-1670-4d3c-9817-5298a4b1eebd

May, Jonathan P., Hysi, Eno, Wirtzfeld, Lauren A., Undzys, Elijus, Li, Shyh Dar and Kolios, Michael C. (2016) Photoacoustic imaging of cancer treatment response: Early detection of therapeutic effect from thermosensitive liposomes. PLoS ONE, 11 (10), [e0165345]. (doi:10.1371/journal.pone.0165345).

Record type: Article

Abstract

Imaging methods capable of indicating the potential for success of an individualized treatment course, during or immediately following the treatment, could improve therapeutic outcomes. Temperature Sensitive Liposomes (TSLs) provide an effective way to deliver chemotherapeutics to a localized tumoral area heated to mild-hyperthermia (HT). The high drug levels reached in the tumor vasculature lead to increased tumor regression via the cascade of events during and immediately following treatment. For a TSL carrying doxorubicin (DOX) these include the rapid and intense exposure of endothelial cells to high drug concentrations, hemorrhage, blood coagulation and vascular shutdown. In this study, ultrasound-guided photoacoustic imaging was used to probe the changes to tumors following treatment with the TSL, HaT-DOX (Heat activated cytoToxic). Levels of oxygen saturation (sO2) were studied in a longitudinal manner, from 30 min pre-treatment to 7 days post-treatment. The efficacious treatments of HT-HaT-DOX were shown to induce a significant drop in sO2 (>10%) as early as 30 min post-treatment that led to tumor regression (in 90% of cases); HT-Saline and non-efficacious HT-HaT-DOX (10% of cases) treatments did not show any significant change in sO2 at these timepoints. The changes in sO2 were further corroborated with histological data, using the vascular and perfusion markers CD31 and FITC-lectin. These results allowed us to further surmise a plausible mechanism of the cellular events taking place in the TSL treated tumor regions over the first 24 hours post-treatment. The potential for using photoacoustic imaging to measure tumor sO2 as a surrogate prognostic marker for predicting therapeutic outcome with a TSL treatment is demonstrated.

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Published date: October 2016

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Local EPrints ID: 455592
URI: http://eprints.soton.ac.uk/id/eprint/455592
ISSN: 1932-6203
PURE UUID: a98c9896-64a8-4632-94b2-bc9b4b093ba1
ORCID for Jonathan P. May: ORCID iD orcid.org/0000-0003-1651-130X

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Date deposited: 28 Mar 2022 16:44
Last modified: 27 Apr 2022 02:13

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Contributors

Author: Jonathan P. May ORCID iD
Author: Eno Hysi
Author: Lauren A. Wirtzfeld
Author: Elijus Undzys
Author: Shyh Dar Li
Author: Michael C. Kolios

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