Pharmacokinetics of ICG and HPPH-car for the Detection of Normal and Tumor Tissue Using Fluorescence, Near-infrared Reflectance Imaging: A Case Study¶

Abstract

We present in vivo fluorescent, near-infrared (NIR), reflectance images of indocyanine green (ICG) and carotene-conjugated 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide (HPPH-car) to discriminate spontaneous canine adenocarcinoma from normal mammary tissue. Following intravenous administration of 1.0 mg kg-1 ICG or 0.3 mg kg-1 HPPH-car into the canine, a 25 mW, 778 nm or 70 mW, 660 nm laser diode beam, expanded by a diverging lens to approximately 4 cm in diameter, illuminated the surface of the mammary tissue. Successfully propagating to the tissue surface, ICG or HPPH-car fluorescence generated from within the tissue was collected by an image-intensified, charge-coupled device camera fitted with an 830 or 710 nm bandpass interference filter. Upon collecting time-dependent fluorescence images at the tissue surface overlying both normal and diseased tissue volumes, and fitting these images to a pharmacokinetic model describing the uptake (wash-in) and release (wash-out) of fluorescent dye, the pharmacokinetics of fluorescent dye was spatially determined. Mapping the fluorescence intensity owing to ICG indicates that the dye acts as a blood pool or blood persistent agent, for the model parameters show no difference in the ICG uptake rates between normal and diseased tissue regions. The wash-out of ICG was delayed for up to 72 h after intravenous injection in tissue volumes associated with disease, because ICG fluorescence was still detected in the diseased tissue 72 h after injection. In contrast, HPPH-car pharmacokinetics illustrated active uptake into diseased tissues, perhaps owing to the overexpression of LDL receptors associated with the malignant cells. HPPH-car fluorescence was not discernable after 24 h. This work illustrates the ability to monitor the pharmacokinetic delivery of NIR fluorescent dyes within tissue volumes as great as 0.5-1 cm from the tissue surface in order to differentiate normal from diseased tissue volumes on the basis of parameters obtained from the pharmacokinetic models.

Effets de la fluorescence résiduelle dans les tissus biologiques sur les signaux de fluorescence résolus temporellement par la méthode des éléments finis

“…Le temps de vie des fluorophores est τ = 1 ns et le rendement quantique est ψ = 20 % ce qui correspond aux propriétés du Cyanine 5,5 (Cy5,5) utilisé expérimentalement[18,19].…”

Optical Imaging and Measurement of Angiogenesis

“…Gurfinkel et al used indocyanine green dye and carotene-conjugated 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide (HPPH-car) as contrast agents for NIR fluorescence reflectance imaging of tumors in a spontaneous canine mammary adenocarcinoma [86]. While indocyanine green is a small molecule with a molecular weight of 775, it readily binds to albumin and other plasma proteins upon intravenous injection [87]; thus, for permeability studies, indocyanine green bound to plasma proteins behaves essentially like a macromolecule.…”

Combined MR and Optical Imaging System for Noninvasive Tumor Characterization and Quantification of Oxygenation Gain Factor in a Breast Cancer Animal Model

“…(Gurfinkel et al 2000) presented a double exponential, four-parameter model to describe uptake of ICG and employed a fluorescence reflectance imaging system for the measurements in small animal models. However, they did not detect a difference in the ICG uptake rates between normal and neoplastic tissue.…”