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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 tumora... Full description

Journal Title: PLoS ONE 2016, Vol.11(10)
Main Author: May, Jonathan P
Other Authors: Hysi, Eno , Wirtzfeld, Lauren A , Undzys, Elijus , Li, Shyh-Dar , Kolios, Michael C
Format: Electronic Article Electronic Article
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ID: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0165345 ; PMCID: 5082794 ; PMID: 27788199
Link: pone.0165345.pdf
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recordid: pubmed_central5082794
title: Photoacoustic Imaging of Cancer Treatment Response: Early Detection of Therapeutic Effect from Thermosensitive Liposomes
format: Article
creator:
  • May, Jonathan P
  • Hysi, Eno
  • Wirtzfeld, Lauren A
  • Undzys, Elijus
  • Li, Shyh-Dar
  • Kolios, Michael C
subjects:
  • Research Article
  • Medicine And Health Sciences
  • Biology And Life Sciences
  • Physical Sciences
  • Medicine And Health Sciences
  • Research And Analysis Methods
  • Medicine And Health Sciences
  • Biology And Life Sciences
  • Medicine And Health Sciences
  • Biology And Life Sciences
  • Medicine And Health Sciences
  • Medicine And Health Sciences
  • Research And Analysis Methods
  • Medicine And Health Sciences
  • Research And Analysis Methods
  • Medicine And Health Sciences
  • Biology And Life Sciences
  • Medicine And Health Sciences
ispartof: PLoS ONE, 2016, Vol.11(10)
description: 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 ( H eat a ctivated cyto T oxic). Levels of oxygen saturation (sO 2 ) 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 sO 2 (>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 sO 2 at these timepoints. The changes in sO 2 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 sO 2 as a surrogate prognostic marker for predicting therapeutic outcome with a TSL treatment is demonstrated.
language:
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identifier: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0165345 ; PMCID: 5082794 ; PMID: 27788199
fulltext: fulltext
issn:
  • 1932-6203
  • 19326203
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descriptionImaging 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 ( H eat a ctivated cyto T oxic). Levels of oxygen saturation (sO 2 ) 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 sO 2 (>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 sO 2 at these timepoints. The changes in sO 2 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 sO 2 as a surrogate prognostic marker for predicting therapeutic outcome with a TSL treatment is demonstrated.
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abstractImaging 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 ( H eat a ctivated cyto T oxic). Levels of oxygen saturation (sO 2 ) 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 sO 2 (>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 sO 2 at these timepoints. The changes in sO 2 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 sO 2 as a surrogate prognostic marker for predicting therapeutic outcome with a TSL treatment is demonstrated.
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date2016-10-27