Molecular Photoacoustic Imaging of Follicular Thyroid Carcinoma

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.

Photoacoustic lifetime contrast between methylene blue monomers and self-quenched dimers as a model for dual-labeled activatable probes

“…[41][42][43][44] Based on the previous measurements, we propose a new mechanism for an activatable photoacoustic probe. In its simplest form, the probe relies on a custom-made peptide linker bearing a specific enzymatic site and confining two MB molecules to a dimer configuration.…”

Structural and functional photoacoustic molecular tomography aided by emerging contrast agents

“…The system equipped with a 21 MHz linear array provides three dimensional (3D) visualization, tumor imaging and oxygen saturation measurement. 49 A 590-element PVDF plane array transducer has been used in the Twente PA mammoscope for clinical trials of human breast imaging. 50,51 The downside is that the scan time is relatively long (~30 min per frame) and the spatial resolution (2–4 mm) demands further improvement.…”

Multiscale Functional and Molecular Photoacoustic Tomography

“…Magnetically modulated PA detection can highlight the signals from magnetic nanoparticles targeted to tumor cells [142]. Activatable organic dyes and nanoparticles can also help detect cellular activities of interest, with improved sensitivity (Figure 3f) [54, 156]. …”

“…Inset: epi-fluorescence image of the mouse showing the ILN location. (f) PAT of the activatable B-APP-A in a FTC133 tumor in the mouse hind leg after tail vein injection of B-APP-A (top) and the control probe (bottom) [54]. Images were adapted with permission from references [7, 54, 160, 209–211].…”