In vivo mouse fluorescence imaging for folate-targeted delivery and release kinetics

Abstract

Many cancer cells over-express folate receptors, and this provides an opportunity for both folate-targeted fluorescence imaging and the development of targeted anti-cancer drugs. We present an optical imaging modality that allows for the monitoring and evaluation of drug delivery and release through disulfide bond reduction inside a tumor in vivo for the first time. A near-infrared folate-targeting fluorophore pair was synthesized and used to image a xenograft tumor grown from KB cells in a live mouse. The in vivo results are shown to be in agreement with previous in vitro studies, confirming the validity and feasibility of our method as an effective tool for preclinical studies in drug development.

Fabrication and application of heterogeneous printed mouse phantoms for whole animal optical imaging

“…Data were captured from the printed mice for reconstruction using an automated version of the measurement setup we have used previously for live mouse imaging [6]. The setup is shown in Fig.…”

“…An unstructured finite element mesh was generated using TetGen [32] using 22,489 nodes (4881 surface nodes) from a subset of the Digimouse data. Alternatively, the 3D line scan could have been used to generate the mesh, as we have done previously for imaging mice where the 3D surface profile is not known [6,27], however, the mesh generated from the Digimouse data is more accurate as it was used to print the mouse. For reconstruction, images were formed on a Cartesian grid with voxel size (1 mm) 3 and a nonlinear conjugate gradient iterative solver was used with first-order Tikhonov regularization.…”

“…A rich spectrum of methods relying on the coherent or incoherent properties of light have been developed for applications ranging from focusing light through scatter [1–3] to protein folding and anticancer drug pharmacokinetics studies [4–6] to brain imaging [7–9]. The great challenge for these methods is overcoming the deleterious effects of scatter and absorption, which randomize the propagation direction of light and tend to decrease image resolution and quality.…”

“…In contrast, the phantoms fabricated here are for deep tissue ( > 2 cm depth, the location of major organs) imaging and the development of diffuse optical tomography (DOT) [15–18]. DOT is a whole animal optical imaging modality, allowing, for example, the determination of tumor sizes and locations [19], pharmacokinetic rates [6], and whole brain activation maps [20]. We note, however, that there is copious room to explore the uses of 3D printing for other imaging methods.…”

Diffuse optical localization of blood vessels and 3D printing for guiding oral surgery

“…Instrumentation for DOI is typically inexpensive and safe, and related technology has been used to develop the highly successful pulse oximetry devices [3]. In DOI methods such as diffuse optical tomography (DOT), near-infrared or visible light is used to form volumetric images in deep (>1 cm) tissue by treating photons as diffusing particles [4–6]. However, this is a computationally intensive process, limiting its application in surgery, where information is often needed in real time.…”