Molecular photoacoustic imaging of follicular thyroid carcinoma

Jelena Levi, Sri Rajashekar Kothapalli, Sarah Bohndiek, Joon Kee Yoon, Anca Dragulescu-Andrasi, Carsten Nielsen, Aleksandra Tisma, Sunil Bodapati, Gayatri Gowrishankar, Xinrui Yan, Carmel Chan, Daniela Starcevic, Sanjiv Sam Gambhir

Research output: Contribution to journalArticle

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Abstract

Purpose: To evaluate the potential of targeted photoacoustic imaging as a noninvasive method for detection of follicular thyroid carcinoma. Experimental Design: We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP-activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP-activatable agent was imaged after intratumoral and intravenous injections in living mice optically, observing the increase in Alexa750 fluorescence, and photoacoustically, using a dual-wavelength imaging method. Results: Active forms of both MMP-2 and MMP-9 enzymes were found in FTC133 tumor homogenates, with MMP-9 detected in greater amounts. The molecular imaging agent was determined to be activated by both enzymes in vitro, with MMP-9 being more efficient in this regard. Both optical and photoacoustic imaging showed significantly higher signal in tumors of mice injected with the active agent than in tumors injected with the control, nonactivatable, agent. Conclusions: With the combination of high spatial resolution and signal specificity, targeted photoacoustic imaging holds great promise as a noninvasive method for early diagnosis of follicular thyroid carcinomas.

Original languageEnglish (US)
Pages (from-to)1494-1502
Number of pages9
JournalClinical Cancer Research
Volume19
Issue number6
DOIs
StatePublished - Mar 15 2013

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Follicular Adenocarcinoma
Molecular Imaging
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Matrix Metalloproteinase 2
Neoplasms
Thyroid Gland
Optical Imaging
Enzymes
Nude Mice
Intravenous Injections
Early Diagnosis
Research Design
Biomarkers
Fluorescence

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Levi, J., Kothapalli, S. R., Bohndiek, S., Yoon, J. K., Dragulescu-Andrasi, A., Nielsen, C., ... Gambhir, S. S. (2013). Molecular photoacoustic imaging of follicular thyroid carcinoma. Clinical Cancer Research, 19(6), 1494-1502. https://doi.org/10.1158/1078-0432.CCR-12-3061
Levi, Jelena ; Kothapalli, Sri Rajashekar ; Bohndiek, Sarah ; Yoon, Joon Kee ; Dragulescu-Andrasi, Anca ; Nielsen, Carsten ; Tisma, Aleksandra ; Bodapati, Sunil ; Gowrishankar, Gayatri ; Yan, Xinrui ; Chan, Carmel ; Starcevic, Daniela ; Gambhir, Sanjiv Sam. / Molecular photoacoustic imaging of follicular thyroid carcinoma. In: Clinical Cancer Research. 2013 ; Vol. 19, No. 6. pp. 1494-1502.
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abstract = "Purpose: To evaluate the potential of targeted photoacoustic imaging as a noninvasive method for detection of follicular thyroid carcinoma. Experimental Design: We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP-activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP-activatable agent was imaged after intratumoral and intravenous injections in living mice optically, observing the increase in Alexa750 fluorescence, and photoacoustically, using a dual-wavelength imaging method. Results: Active forms of both MMP-2 and MMP-9 enzymes were found in FTC133 tumor homogenates, with MMP-9 detected in greater amounts. The molecular imaging agent was determined to be activated by both enzymes in vitro, with MMP-9 being more efficient in this regard. Both optical and photoacoustic imaging showed significantly higher signal in tumors of mice injected with the active agent than in tumors injected with the control, nonactivatable, agent. Conclusions: With the combination of high spatial resolution and signal specificity, targeted photoacoustic imaging holds great promise as a noninvasive method for early diagnosis of follicular thyroid carcinomas.",
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Levi, J, Kothapalli, SR, Bohndiek, S, Yoon, JK, Dragulescu-Andrasi, A, Nielsen, C, Tisma, A, Bodapati, S, Gowrishankar, G, Yan, X, Chan, C, Starcevic, D & Gambhir, SS 2013, 'Molecular photoacoustic imaging of follicular thyroid carcinoma', Clinical Cancer Research, vol. 19, no. 6, pp. 1494-1502. https://doi.org/10.1158/1078-0432.CCR-12-3061

Molecular photoacoustic imaging of follicular thyroid carcinoma. / Levi, Jelena; Kothapalli, Sri Rajashekar; Bohndiek, Sarah; Yoon, Joon Kee; Dragulescu-Andrasi, Anca; Nielsen, Carsten; Tisma, Aleksandra; Bodapati, Sunil; Gowrishankar, Gayatri; Yan, Xinrui; Chan, Carmel; Starcevic, Daniela; Gambhir, Sanjiv Sam.

In: Clinical Cancer Research, Vol. 19, No. 6, 15.03.2013, p. 1494-1502.

Research output: Contribution to journalArticle

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T1 - Molecular photoacoustic imaging of follicular thyroid carcinoma

AU - Levi, Jelena

AU - Kothapalli, Sri Rajashekar

AU - Bohndiek, Sarah

AU - Yoon, Joon Kee

AU - Dragulescu-Andrasi, Anca

AU - Nielsen, Carsten

AU - Tisma, Aleksandra

AU - Bodapati, Sunil

AU - Gowrishankar, Gayatri

AU - Yan, Xinrui

AU - Chan, Carmel

AU - Starcevic, Daniela

AU - Gambhir, Sanjiv Sam

PY - 2013/3/15

Y1 - 2013/3/15

N2 - Purpose: To evaluate the potential of targeted photoacoustic imaging as a noninvasive method for detection of follicular thyroid carcinoma. Experimental Design: We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP-activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP-activatable agent was imaged after intratumoral and intravenous injections in living mice optically, observing the increase in Alexa750 fluorescence, and photoacoustically, using a dual-wavelength imaging method. Results: Active forms of both MMP-2 and MMP-9 enzymes were found in FTC133 tumor homogenates, with MMP-9 detected in greater amounts. The molecular imaging agent was determined to be activated by both enzymes in vitro, with MMP-9 being more efficient in this regard. Both optical and photoacoustic imaging showed significantly higher signal in tumors of mice injected with the active agent than in tumors injected with the control, nonactivatable, agent. Conclusions: With the combination of high spatial resolution and signal specificity, targeted photoacoustic imaging holds great promise as a noninvasive method for early diagnosis of follicular thyroid carcinomas.

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Levi J, Kothapalli SR, Bohndiek S, Yoon JK, Dragulescu-Andrasi A, Nielsen C et al. Molecular photoacoustic imaging of follicular thyroid carcinoma. Clinical Cancer Research. 2013 Mar 15;19(6):1494-1502. https://doi.org/10.1158/1078-0432.CCR-12-3061