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Britton Chance

Publications and source records attributed to Britton Chance.

66 records · Page 4Linked to original sources
PubMedDate not supplied

Low-density lipoprotein reconstituted by pyropheophorbide cholesteryl oleate as target-specific photosensitizer.

To target tumors overexpressing low-density lipoprotein receptors (LDLr), a pyropheophorbide cholesterol oleate conjugate was synthesized and successfully reconstituted into the low-density lipoprotein (LDL) lipid core. Laser scanning confocal microscopy studies demonstrated that this photosensitizer-reconstituted LDL can be internalized via LDLr by human hepatoblastoma G(2) (HepG(2)) tumor cells.

Binding, Competitive↗
PubMedDate not supplied

Pyropheophorbide 2-deoxyglucosamide: a new photosensitizer targeting glucose transporters.

To prepare near-infrared fluorescence imaging and photodynamic therapy agents targeted at glucose transporters, pyropheophorbide 2-deoxyglucosamide (Pyro-2DG) was synthesized and evaluated in a 9L glioma rat model. Fluorescence imaging studies demonstrate that Pyro-2DG is selectively accumulated in the tumor. Upon its photoactivation, we demonstrate that this agent efficiently causes selective mitochondrial damage to the region of a tumor that was photoirradiated after administration of this agent, but does not affect tissues photoirradiated in the absence of the agent or tissues treated with the agent that are not photoirradiated. Preliminary confocal microscopy studies suggest that Pyro-2DG is delivered and trapped in tumor cells via the GLUT/hexokinase pathway and therefore is useful both as a tumor-targeted NIR fluorescence imaging probe and as a PDT agent for the destruction of cancer.

Animals↗
PubMedDate not supplied

A novel approach to a bifunctional photosensitizer for tumor imaging and phototherapy.

Optical imaging has attracted a great attention for studying molecular recognitions because minute fluorescent tracers can be detected in homogeneous and heterogeneous media with existing laboratory instruments. In our preliminary study, a clinically relevant photosensitizer (HPPH, a chlorophyll-a analog) was linked with a cyanine dye (with required photophysical characteristics but limited tumor selectivity), and the resulting conjugate was found to be an efficient tumor imaging (fluorescence imaging) and photosensitizing agent. Compared to HPPH, the presence of the cyanine dye moiety in the conjugate produced a significantly higher uptake in tumor than skin. At a therapeutic/imaging dose, the conjugate did not show any significant skin phototoxicity, a major drawback associated with most of the porphyrin-based photosensitizers. These results suggest that tumor-avid porphyrin-based compounds can be used as "vehicles" to deliver the desired fluorescent agent(s) to tumor. The development of tumor imaging or improved photodynamic therapy agent(s) by itself represents an important step, but a dual function agent (fluorescence imaging and photodynamic therapy) provides the potential for tumor detection and targeted photodynamic therapy, combining two modalities into a single cost-effective "see and treat" approach.

Animals↗
PubMedDate not supplied

MRI-guided diffuse optical spectroscopy of malignant and benign breast lesions.

We present the clinical implementation of a novel hybrid system that combines magnetic resonance imaging (MRI) and near-infrared (NIR) optical measurements for the noninvasive study of breast cancer in vivo. Fourteen patients were studied with a MR-NIR prototype imager and spectrometer. A diffuse optical tomographic scheme employed the MR images as a priori information to implement an image-guided NIR localized spectroscopic scheme. All patients who entered the study also underwent gadolinium-enhanced MRI and biopsy so that the optical findings were cross-validated with MR readings and histopathology. The technique quantified the oxy- and deoxyhemoglobin of five malignant and nine benign breast lesions in vivo. Breast cancers were found with decreased oxygen saturation and higher blood concentration than most benign lesions. The average hemoglobin concentration ([H]) of cancers was 0.130+/-0.100 mM, and the average hemoglobin saturation (Y) was 60+/-9% compared to [H]=0.018+/-0.005 mM and Y=69+/-6% of background tissue. Fibroadenomas exhibited high hemoglobin concentration [H]=0.060+/-0.010 mM and mild decrease in oxygen saturation Y=67+/-2%. Cysts and other normal lesions were easily differentiated based on intrinsic contrast information. This novel optical technology can be a significant add-on in MR examinations and can be used to characterize functional parameters of cancers with diagnostic and treatment prognosis potential. It is foreseen that the technique can play a major role in functional activation studies of brain and muscle as well.

Biopsy↗
PubMedDate not supplied

Redox ratio of mitochondria as an indicator for the response of photodynamic therapy.

The effect of photodynamic therapy (PDT) treatment on the metabolic state of tumor mitochondria is investigated by imaging of tumor redox status. PDT is performed using the photosensitizer pyropheophorbide-2-deoxyglucosamide (Pyro-2DG), which utilizes the glucose import pathway. It is found that Pyro-2DG-induced PDT resulting in a highly oxidized state of tumor mitochondria. This is determined from the redox ratio changes derived from the intrinsic oxidized flavoprotein (Fp) and reduced pyridine nucleotide (PN) [i.e., reduced nicotinamide adenine dinucleotide (NADH)] fluorescence signals observed using a cryoimager. Thus, the redox ratio is a sensitive indicator for providing reliable and informative measurements of PDT-induced tissue damage. In the PDT treated region of the tumor, highly oxidized flavoprotein and diminishing NADH fluorescence is detected, suggesting that flavoprotein and NADH are oxidized by singlet oxygen produced in the photosensitization process.

Animals↗
PubMedDate not supplied

Time-dependent blood flow and oxygenation in human skeletal muscles measured with noninvasive near-infrared diffuse optical spectroscopies.

We have employed near-infrared optical methods to measure noninvasively the dynamics of muscle blood flow and oxygen saturation (StO2) during cuff occlusion and plantar flexion exercise. Relative muscle oxygen consumption (rVO2) was also computed from these data. Diffuse correlation spectroscopy provides information about blood flow, and diffuse reflectance spectroscopy provides information about blood oxygenation. Ten healthy subjects and one patient with peripheral arterial disease (PAD) were studied during 3-min arterial cuff occlusion of arm and leg, and during 1-min plantar flexion exercise. Signals from different layers (cutaneous tissues and muscles) during cuff occlusion were differentiated, revealing strong hemodynamic responses from muscle layers. During exercise in healthy legs, the observed approximately 4.7 fold increase in relative blood flow (rBF) was significantly lower than the corresponding increase in rVO2 (approximately 7 fold). The magnitudes of rBF and rVO2 during exercise in the PAD patient were approximately 1/2 of the healthy controls, and the StO2 recovery time was twice that of the controls. The hybrid instrument improves upon current technologies for measuring muscle responses by simultaneously measuring rBF and StO2. The instrument thus provides a method for evaluation of microcirculation and muscle metabolism in patients with vascular diseases.

Adult↗
PubMedDate not supplied

In vivo determination of the optical properties of infant brain using frequency-domain near-infrared spectroscopy.

We investigate the optical properties of the brain in 23 neonates in vivo using a frequency domain near-infrared spectroscopy (NIRS). In this study, a calibration procedure is employed to determine the absorption and reduced scattering coefficients with single source-detector separation. The absorption coefficients of the infant foreheads are lower than the values reported in adults. A large intersubject variation in the reduced scattering coefficients is also demonstrated. Furthermore, physiological parameters are derived from the absorption coefficients at two wavelengths (788 and 832 nm). The mean total hemoglobin concentration (THC) is 39.7+/-9.8 microM and the mean cerebral blood oxygen saturation (StO2) is 58.7+/-11.2%. Our preliminary results show that this bedside frequent domain NIRS could provide quantitative optical measurement of the infant brain.

Absorption↗
PubMedDate not supplied

Effect of errors in baseline optical properties on accuracy of transabdominal near-infrared spectroscopy in fetal sheep brain during hypoxic stress.

A continuous-wave (cw) near-infrared spectroscopy (NIRS) instrument has been developed to noninvasively quantify fetal cerebral blood oxygen saturation (StO2). A linear Green's function formulism was used to analytically solve the photon diffusion equation and extract the time-varying fetal tissue oxy- and deoxy-hemoglobin concentrations from the NIR measurements. Here we explored the accuracy with which this instrument can be expected to perform over a range of fetal hypoxic states. We investigated the dependence of this accuracy on the accuracy of the reference optical properties chosen based on the literature. The fetal oxygenation of a pregnant ewe model was altered via maternal aortic occlusion. The NIR cw instrument was placed on the maternal abdomen directly above the fetal head, continuously acquiring diffuse optical measurements. Blood was sampled periodically from the fetus to obtain fetal arterial saturation (SaO2) measurements from blood gas analysis. The NIR StO2 values were compared with the fetal SaO2 measurements. Variations in the NIR results due to uncertainty in the reference optical properties were relatively small within the fetal SaO2 range of 30 to 80%. Under hypoxic conditions, however, the variability of the NIR StO2 calculations with changes in the assumed reference properties became more significant.

Abdomen↗
PubMedDate not supplied

Noninvasive diffuse optical measurement of blood flow and blood oxygenation for monitoring radiation therapy in patients with head and neck tumors: a pilot study.

This pilot study explores the potential of noninvasive diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS) for monitoring early relative blood flow (rBF), tissue oxygen saturation (StO(2)), and total hemoglobin concentration (THC) responses to chemo-radiation therapy in patients with head and neck tumors. rBF, StO(2), and THC in superficial neck tumor nodes of eight patients are measured before and during the chemo-radiation therapy period. The weekly rBF, StO(2), and THC kinetics exhibit different patterns for different individuals, including significant early blood flow changes during the first two weeks. Averaged blood flow increases (52.7+/-9.7)% in the first week and decreases (42.4+/-7.0)% in the second week. Averaged StO(2) increases from (62.9+/-3.4)% baseline value to (70.4+/-3.2)% at the end of the second week, and averaged THC exhibits a continuous decrease from pretreatment value of (80.7+/-7.0) [microM] to (73.3+/-8.3) [microM] at the end of the second week and to (63.0+/-8.1) [microM] at the end of the fourth week of therapy. These preliminary results suggest daily diffuse-optics-based therapy monitoring is feasible during the first two weeks and may have clinical promise.

Aged↗
PubMedDate not supplied

Fluorescence spectroscopy and imaging of myocardial apoptosis.

Fluorometry is used to detect intrinsic flavoprotein (FP) and nicotinamide adenine dinucleotide (NADH) signals in an open-chest rabbit model of myocardial ischemia-reperfusion injury. Myocyte apoptosis has been shown clinically to contribute to infarct size following reperfusion of ischemic myocardium. A noninvasive means of assessing apoptosis in this setting would aid in the treatment of subsequent ventricular remodeling. We show that in vivo fluorometry can be useful in apoptosis detection in open-chest surgeries. Specific changes in myocardial redox states have been shown to indicate the presence of apoptosis. Two main mitochondrial intrinsic fluorophores, NADH and FP signals, were measured during normoxia, ischemia, and reperfusion experimental protocol. Ischemia was induced by occlusion of the largest branch of the circumflex coronary artery and fluorescence signals are collected by applying two different fluorescence techniques: in vivo fluorometry and postmortem cryoimaging. The first technique was employed to detect FP and NADH signals in vivo and the latter technique uses freeze trapping and low-temperature fluorescence imaging. The heart is snap frozen while still in the chest cavity to make a "snapshot" of the metabolic state of the tissue. After freezing, the ischemic area and its surrounding border zone were excised and the sample was embedded in a frozen buffer for cryoscanning. These two data sets, in vivo fluorometry and low-temperature redox scanning, show consistent extreme oxidation of the mitochondrial redox states (higher redox ratio) suggesting the initiation of apoptosis following reperfusion. This represents the first attempt to assess myocyte apoptosis in the beating heart.

Animals↗
PubMedDate not supplied

Development of high-sensitivity near-infrared fluorescence imaging device for early cancer detection.

We have developed a high-sensitivity near-infrared (NIR) optical imaging system for noninvasive cancer detection based on the molecular-labeled fluorescent contrast agents. Recent developments in molecular beacons offer a way to selectively tag various precancer and cancer signatures and provide high tumor-to-background contrast. Near-infrared imaging can deeply probe tissue up to a couple of centimeters; thus, it possesses the potential for noninvasive detection of breast or lymph node cancer. A phase cancellation (in- and antiphase) device is used to increase the sensitivity in detecting fluorescent photons and the accuracy of tumor localization. The optoelectronic system consists of the laser diode sources, fiber optics, interference filter (to select the fluorescent photons), and the high-sensitivity photon detector (photomultiplier tube). The source-detector pair scans the tissue surface in multiple directions, and the localization image can be obtained by angular back-projection reconstruction. Simulations and experimental data demonstrated the feasibility of detection and localization offluorescent object embedded inside the highly scattering media. Tumor-bearing mouse model with injection of fluorescent contrast agents is used to simulate the human breast tumor labeled with molecular beacons. The system can detect fluorescent contrast agents as small as one nanomole at the depth of three centimeters, with a three-millimeter localization error. This instrument has the potential for tumor diagnosis and imaging, and the accuracy of the localization suggests that this system could help guide the clinical fine-needle biopsy. Also, this portable device would be complementary to x-ray mammography and provide add-on information on early diagnosis and localization of breast tumor.

Animals↗