Currently, surgeons mainly rely on palpation and visual inspection due to the difficulties oftranslating findings of nuclear medicine to the operating room due to the general lack oflandmarks to orient the prior nuclear medicine results. Therefore, there is a critical need for newintraoperative imaging modalities that can provide accurate, real-time, intraoperativeassessment of both molecular and anatomical information resulting in identification of viabletumor, fibrotic (scar) tissue, non-malignant tissue, and tumor margins at greater depths than areavailable with infrared-fluorescent guided surgery as well as better resolution than endoscopy.To overcome these limitations, our objective is to develop, characterize, and validate ultra-acidicpH-responsive optoacoustic dye (pHO dye) detectable by multispectral optoacoustictomography (MSOT) and provide real-time color maps of tissue pH to allow for identification ofregions of tumor and non-malignant tissue in mice. Three innovative aspects in this proposalare: 1) development, characterization, and evaluation of the first zwitterionic optoacousticcontrast agent, prototype pHO dye, that modulates spectra in response to ? 0.2 pHe of thetissue microenvironment; 2) use of unique instrumentation, multispectral optoacoustictomography, which provides superior resolution, penetration depth, and the ability to visualizemultiple spectra simultaneously; 3) development and validation of ratiometric algorithm forgeneration of real-time acidic pHe color maps based upon detection of pHO dye or V7-pHOprobe via MSOT imaging.We hypothesize that optimized pHO dye and V7-pHO probe will facilitate detection of tumorand differentiate it from non-malignant and fibrous tissue with high sensitivity and specificityusing multispectral optoacoustic tomography (MSOT) which utilizes a ?light-excitation andsound-emission? approach resulting in superior signal to background ratio. We will test thishypothesis by the following aims: 1) characterize, optimize, and validate pHO dye and V7-pHOprobe to target acidic pHe for detection of tumor cells in vitro and in tissue phantoms; 2) assessoptimized pHO dye and V7-pHO probe to facilitate detection of orthotopic tumors from non-malignant tissue in vivo using multispectral optoacoustic tomography; 3) develop ratiometricalgorithms based upon the spectral modulation of the optimized pHO dye and V7-pHO probe toproduce real-time pHe measurement color maps of tumors. Successful completion of thisproposal will result in unprecedented improvements in detection of abdominal tumors in vivo topotentially reduce the gap between the surgeon and nuclear imaging.
It is critical to develop intraoperative imaging methods to accurately identify tumor anddetermine its molecular features at depths of centimeters with resolution of to substantiallyimpact surgical resections. This proposal will develop; characterize; and evaluate twoextracellular acidic pH contrast agents; pHO dye and V7-pHO probe; as agents to facilitatetumor detection via multispectral optoacoustic tomography. Successful completion of thisapplication has broad application to improved resection of abdominal tumors.
| Samykutty, A; Thomas, A; McNally, M et al. (2018) Osteopontin-targeted probe detects orthotopic breast cancers using optoacoustic imaging. Biotech Histochem 93:608-614 |
| Xiao, Ted G; Weis, Jared A; Gayzik, F Scott et al. (2018) Applying dynamic contrast enhanced MSOT imaging to intratumoral pharmacokinetic modeling. Photoacoustics 11:28-35 |
| Samykutty, Abhilash; Grizzle, William E; Fouts, Benjamin L et al. (2018) Optoacoustic imaging identifies ovarian cancer using a microenvironment targeted theranostic wormhole mesoporous silica nanoparticle. Biomaterials 182:114-126 |
| Bhutiani, N; Kimbrough, C W; Burton, N C et al. (2017) Detection of microspheres in vivo using multispectral optoacoustic tomography. Biotech Histochem 92:1-6 |
| Bhutiani, Neal; Grizzle, William E; Galandiuk, Susan et al. (2017) Noninvasive Imaging of Colitis Using Multispectral Optoacoustic Tomography. J Nucl Med 58:1009-1012 |
