TY - JOUR

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 Haagen

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 - PurposeTo evaluate the potential of targeted photoacoustic imaging as a non-invasive method for detection of follicular thyroid carcinoma.Experimental DesignWe 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.ResultsActive forms of both MMP2 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, non-activatable, agent.ConclusionsWith 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.

AB - PurposeTo evaluate the potential of targeted photoacoustic imaging as a non-invasive method for detection of follicular thyroid carcinoma.Experimental DesignWe 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.ResultsActive forms of both MMP2 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, non-activatable, agent.ConclusionsWith 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.

U2 - 10.1158/1078-0432.CCR-12-3061

DO - 10.1158/1078-0432.CCR-12-3061

M3 - Journal article

C2 - 23349314

VL - 19

SP - 1494

EP - 1502

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 6

ER -