Molecular photoacoustic imaging of follicular thyroid carcinoma.
OBJECTIVE
To evaluate the potential of targeted photoacoustic imaging as a noninvasive method for detection of follicular thyroid carcinoma.


METHODS
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.
Canary Center at Stanford for Cancer Early Detection, Stanford University, Palo Alto, California 94305, USA.
Jelena
J
Levi
Sri-Rajashekar
SR
Kothapalli
Sarah
S
Bohndiek
Joon-Kee
JK
Yoon
Anca
A
Dragulescu-Andrasi
Carsten
C
Nielsen
Aleksandra
A
Tisma
Sunil
S
Bodapati
Gayatri
G
Gowrishankar
Xinrui
X
Yan
Carmel
C
Chan
Daniela
D
Starcevic
Sanjiv Sam
SS
Gambhir
D018263:Adenocarcinoma, Follicular / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000302:isolation & purification / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000302:isolation & purification / Q000378:metabolism; D051379:Mice; D057054:Molecular Imaging; D061088:Photoacoustic Techniques; D011859:Radiography
D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9