Fast Multispectral Optoacoustic Tomography (MSOT) for Dynamic Imaging of Pharmacokinetics and Biodistribution in Multiple Organs

Abstract

The characterization of pharmacokinetic and biodistribution profiles is an essential step in the development process of new candidate drugs or imaging agents. Simultaneously, the assessment of organ function related to the uptake and clearance of drugs is of great importance. To this end, we demonstrate an imaging platform capable of high-rate characterization of the dynamics of fluorescent agents in multiple organs using multispectral optoacoustic tomography (MSOT). A spatial resolution of approximately 150 µm through mouse cross-sections allowed us to image blood vessels, the kidneys, the liver and the gall bladder. In particular, MSOT was employed to characterize the removal of indocyanine green from the systemic circulation and its time-resolved uptake in the liver and gallbladder. Furthermore, it was possible to track the uptake of a carboxylate dye in separate regions of the kidneys. The results demonstrate the acquisition of agent concentration metrics at rates of 10 samples per second at a single wavelength and 17 s per multispectral sample with 10 signal averages at each of 5 wavelengths. Overall, such imaging performance introduces previously undocumented capabilities of fast, high resolution in vivo imaging of the fate of optical agents for drug discovery and basic biological research.

Molecular photoacoustic imaging of breast cancer using an actively targeted conjugated polymer

“…These include gold [12][13][14] and silver 15 nanostructures, single-walled carbon nanotubes, 16 and NIR dyes such as indocyanine green. [17][18][19] Although these compounds have shown a certain level of efficacy for imaging purposes, they have some inherent drawbacks, such as complex chemical procedures for tuning of optical properties of gold and silver nanostructures, water insolubility issues of pristine carbon nanotubes, as well as fast body clearance of small dyes, making them unsuitable for longitudinal studies.…”

Simultaneous photoacoustic and optically mediated ultrasound microscopy: an in vivo study

“…To obtain images of the tail vessels, the mouse was fixed in the supine position, while a lateral position was used to obtain images of the internal structure of the mouse. To induce a subcutaneous tumor 5x10 5 of Colo26 cells (murine colorectal carcinoma) suspended in 0.1 mL PBS were injected into the hind flank of the mouse. The experiments began on day 12 after tumor inoculation, when the tumor had a size of 12x7 mm.…”

“…Meanwhile, the optical absorption spectra of endogenous chromophores (hemoglobin [2], melanin [3], lipids [4], etc.) and exogenous markers (organic dyes [5], nanoparticles [6], fluorescent proteins [7], etc.) enable the corresponding PA imaging to have a level of contrast that is unachievable by the US methods alone [8].…”

In vivo cellular-level real-time pharmacokinetic imaging of free-form and liposomal indocyanine green in liver

“…Despite the well-established clinical usage of the ICG and active investigations to utilize the liposomal ICG for novel clinical applications, the dynamic distribution of them after the systemic introduction into the body has been investigated mostly in macroscopic tissue scale and in relatively long-term time scale of several hours to days [20,22,[29][30][31][32]. As the freeform ICG introduced into the human body via intravenous injection in most clinical applications is known to be rapidly cleared out from the blood plasma after several minutes [33], it is desirable to analyze the dynamic pharmacokinetics of ICG during the similar time period of initial several minutes accordingly.…”

“…As the freeform ICG introduced into the human body via intravenous injection in most clinical applications is known to be rapidly cleared out from the blood plasma after several minutes [33], it is desirable to analyze the dynamic pharmacokinetics of ICG during the similar time period of initial several minutes accordingly. In addition, although it has been known that the metabolic clearance of ICG from the blood mostly occurs in the liver [34], revealed by realtime monitoring in macroscopic organ scale [22,[29][30][31][32], a dynamic clearance process of ICG from the liver sinusoid to perisinusoidal space, subsequent cellular-level absorption and distribution in the stromal liver hepatocyte under in vivo environment have not been well understood. It is partially due to the lack of appropriate ICG imaging technique which requires the cellular resolution and fast real-time imaging speed.…”