Concurrent fluorescence and volumetric optoacoustic tomography of nanoagent perfusion and bio-distribution in solid tumors

Abstract

Intravenously administered liposomes and other nano-sized particles are known to passively accumulate in solid tumors via the enhanced permeability and retention (EPR) effect, which is extensively explored toward the improvement of diagnosis and drug delivery in oncology. Agent extravasation into tumors is often hampered by the mononuclear phagocytic and renal systems, which sequester and/or eliminate most of the nanoparticles from the body. Dynamic imaging of the tumor microcirculation and bolus perfusion can thus facilitate optimization of the nanoparticle delivery. When it comes to non-invasive visualization of rapid biological dynamics in whole tumors, the currently available preclinical imaging modalities are commonly limited by shallow penetration, lack of suitable contrast or otherwise insufficient spatial or temporal resolution. Herein, we demonstrate the unique capabilities of a combined epi-fluorescence and optoacoustic tomography (FLOT) system for characterizing contrast agent dynamics in orthotopic breast tumors in mice. A liposomal indocyanine green (Lipo-ICG) preparation was administered intravenously with the time-lapse data continuously acquired during and after the injection procedure. In addition to the highly sensitive detection of the fluorescence agent by the epi-fluorescence modality, the volumetric multi-spectral optoacoustic tomography readings further enabled resolving deepseated vascular structures with high spatial resolution and hence provided accurate readings of the dynamic bio-distribution of nanoparticles in the entire tumor in 3D. The synergetic combination of the two modalities can become a powerful tool in cancer research and potentially aid the diagnosis, staging and treatment guidance of certain types of cancer in the clinical setting.

Skin Barriers in Dermal Drug Delivery: Which Barriers Have to Be Overcome and How Can We Measure Them?

“…To our knowledge there is no current study investigating (trans)-dermal drug delivery by optoacoustic imaging. However, especially from cancer-related research, several examples showed the use of optoacoustic imaging for the detection of fluorescently labelled drugs or drug carriers, like Cy7 conjugated iron oxide nanoparticles (Cy7-SPION) or PEGylated indocyanine green (ICG) liposomes, within experimental tumors such as breast cancer [ 194 , 195 , 196 ]. Interestingly, recent developments suggest the applicability of optoacoustic induced power waves to transiently open the SC and thus to facilitate drug permeation.…”

Multifocal structured illumination optoacoustic microscopy

“…Several important aspects and limitations need to be considered when designing an optimal MSIOAM system. Volumetric OA imaging with spherical arrays is known to benefit from their large angular coverage to enable accurate tomographic OA reconstructions 33,34 . Furthermore, in a spherical array geometry, all the individual elements are directed towards the centre of the FOV, thus facilitating higher sensitivity and better OA image quality compared with standard (e.g., linear or planar) array transducers.…”

Development of Multispectral Optoacoustic Tomography as a Clinically Translatable Modality for Cancer Imaging

“…To use a linearregression unmixing method, the spectra of interest must be predefined, usually as oxyhemoglobin, deoxyhemoglobin, and another agent of interest. Although linear unmixing models are most commonly used, these models assume that wavelength-and depth-dependent fluence issues are uniform and therefore can be neglected (28). Many different unmixing algorithms have been successfully developed to obtain information of interest, but there is no reference standard.…”