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Pharmacokinetics of ICG and HPPH‐car for the Detection of Normal and Tumor Tissue Using Fluorescence, Near‐infrared Reflectance Imaging: A Case Study ¶
Author(s) -
Gurfinkel Michael,
Thompson Alan B.,
Ralston William,
Troy Tamara L.,
Moore Ana L.,
Moore Thomas A.,
Gust J. Devens,
Tatman Derreck,
Reynolds Jeffery S.,
Muggenburg Bruce,
Nikula Kristin,
Pandey Ravindra,
Mayer Ralf H.,
Hawrysz Daniel J.,
SevickMuraca Eva M.
Publication year - 2000
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2000)0720094poiahc2.0.co2
Subject(s) - indocyanine green , fluorescence , chemistry , pharmacokinetics , fluorescence lifetime imaging microscopy , fluorescence microscope , in vivo , microscopy , pathology , biomedical engineering , biophysics , optics , medicine , biology , physics , microbiology and biotechnology
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.