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.

Indocyanine green-enhanced fluorescence for assessing parathyroid perfusion during thyroidectomy

“…Indocyanine green-enhanced fluorescence for assessing parathyroid perfusion during thyroidectomy of visceral blood supply and evaluation of bowel perfusion (1)(2)(3)(4)(5)(6)(7)(8)(9). Injected ICG binds tightly to lipoproteins and is rapidly excreted into the bile (1)(2)(3)(4)(5)(6)(7)(8).…”

“…Recently, indocyanine green (ICG)-enhanced fluorescence has been used to improve visualization and to provide detailed anatomical information during different surgical procedures, especially laparoscopic surgery (1)(2)(3)(4)(5)(6)(7)(8). Fluorescent optical guidance minimizes inadvertent tissue injury while enhancing procedural efficiency (9).…”

“…Indocyanine green is a water-soluble anionic amphiphilic tricarbocyanine dye with a molecular weight of 774.96 Da (1)(2)(3)(4)(5)(6)(7)(8)(9). This dye can be injected into the human bloodstream with practically no adverse effects (10)(11)(12)(13)(14)(15)(16)(17)(18)(19) and becomes fluorescent upon excitation by a laser beam or by light with a wavelength in the near infra-red (NIR) spectrum (approximately 820 nm).…”

In vivo fluorescence imaging of exogenous enzyme activity in the gastrointestinal tract

“…Furthermore, the principle could potentially be adapted to in vivo imaging of larger animals when combined with suitable hardware and computer algorithms. Fluorescence-based imaging has been used for noninvasive lymph node mapping in rabbits (29) and detection of mammary tumors in dogs (30,31) up to 1.5 cm from tissue surface. Moreover, it has been predicted that fluorescence-assisted imaging may permit noninvasive measurements 30-40 cm deep in human tissue (32).…”

A simulation study of the variability of indocyanine green kinetics and using structurala prioriinformation in dynamic contrast enhanced diffuse optical tomography (DCE-DOT)

“…Gurfinkel et al (2000) presented a double exponential, four-parameter model to describe uptake of the 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 the normal and the neoplastic tissue.…”