PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.
This PDF file contains the front matter associated with SPIE Proceedings Volume 12357, including the Title Page, Copyright information, Table of Contents, and Conference Committee information.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Pharmacokinetic and Pharmacodynamic Tomography in Translational Research
This talk will introduce the conference and discuss the program for the day. There will be an emphasis on areas of focus in the program, as well as potential new areas of interest for the conference. The talk will additionally introduce the panel discussion.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Being able to visualize and quantify where the drug and/or excipient resides within a multiphasic formulation, how the drug diffuses and is released from the dosage form, the delivery and disposition of the drug and performance of the dosage form can be a powerful tool towards development of dermal drug products. The presentation will focus on how imaging techniques can be used for evaluation of the dosage form and the availability of the drug/excipients in the different layers of the skin to facilitate drug development.
(Abstract was accepted and redacted last year due to travel restrictions)
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The presentation will address methodological aspects and limits of detection of confocal Raman spectroscopy for use in quantitative in vivo analysis of skin penetration and permeation of topically applied materials. The differences in penetration rate of skin at different anatomical locations will be illustrated as well as the effect of product formulation on the penetration of an active.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Pharmacokinetic and Pharmacodynamic Tomography in Preclinical Research
We investigated the potential of Simultaneous Label-free Autofluorescence Multiharmonic (SLAM) microscopy for quantitative evaluation of cisplatin-induced nephrotoxicity in rats. To determine the structural and functional changes associated with cisplatin treatment occurring over a period of time, rats were euthanized at different time points post-treatment (days 2, 6 and 29), and SLAM images were collected from 4% PFA-fixed sagittal kidney sections. Signs of renal tubular injury including hyaline cast formations were detected in SLAM images obtained from day 6 and 29 time points. This study demonstrated the capability of SLAM for visualization and evaluation of cisplatin-induced nephrotoxicity in a label-free manner.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
The bioequivalence of pharmaceutical formulations is typically demonstrated by assessing the pharmacokinetics (PK) of a generic product relative to a reference listed drug (RLD) product. However, for topical products applied to the skin, it has been historically challenging to quantify the drug concentration at the target site of action, and therefore the applicability of the PK-based approach has been limited. Here, we present a novel approach based on stimulated Raman scattering imaging and data processing via deep learning for image feature extraction and automated analysis of cutaneous PK parameters, which also enables the imaging of drug distribution in real time.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Förster Resonance Energy Transfer (FRET) is a unique biophysical phenomenon that allows for energy transfer to occur between two light-sensitive molecules, e.g., a donor and an acceptor fluorophore. FRET has been leveraged in numerous biomedical applications to monitor molecular interactions at the nanoscale. Previously, we have developed a FRET-based nanometer-range proximity assay (2–10 nm) that measures receptor-ligand protein complexes during internalization and subsequent endocytic trafficking steps in vitro and in vivo. Recently, there has been great interest to perform FRET imaging in vivo, especially in the context of quantifying drug delivery in vivo.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
We introduce and validate a framework for imaging and quantifying active molecule penetration into human skin ex vivo and in vivo. Our approach combines nonlinear imaging microscopy modalities, such as two-photon excited auto-fluorescence (TPEF) and coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS). The imaging framework is exemplified first on topically applied glycerol diluted in various vehicles such as water and xanthan gel and second, on retinol applied on ex vivo excised human skin. The proposed framework allows for the 3D percutaneous monitoring of active cosmetic molecules and their formulation across human skin. We demonstrate the reservoir property of topically applied xanthan gel vehicle that releases glycerol continuously over time together with the hydrophobic penetration of retinol between corneocyte.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Receptor occupancy (RO) correlates the dose of drug administered to the percentage of receptors occupied by the drug compound, which helps decide dosing of drug candidates entering clinical trials, and tailor drug dosage for individualized therapies. However, in vivo measurement of RO in solid tumor is hindered by both tissue properties and technical limitations. Here we present the progress of developing a near-infrared, paired-agent imaging (PAI) approach for real-time measurement of anti-tumor drug RO in vivo. In this study, xenograft murine model with orthotopic tumor implant was imaged using a pair of imaging agent: ABY-029, an affibody-dye conjugate, targeting epidermal growth factor receptor (EGFR), together with IRDye 680LT, a pharmacokinetically similar probe devoid of EGFR specificity. Concentration of tumor EGFR free of drug binding was quantified by binding potential (BP), a parameter calculated from fluorescence signals of the agent pair. We demonstrated that BP was decreased by subsequent administration of drug homolog, indicating drug-EGFR engagement in the tumor. The results demonstrated the ability of PAI to reflect displacement of EGFR-bound ABY-029 by anti-EGFR drug molecules, and the potential to be applied for in vivo RO measurement.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Identification and validation of approaches for evaluation of the bioavailability of a topically applied drug in the skin represent a work-in-progress. Coherent Raman imaging can quantitatively visualize drug and elucidate pharmacokinetics estimates. Here, we imaged and quantified the uptake of tazarotene through distinct skin layers of perfused in vivo and non-perfused ex vivo nude mouse ear. Differences in the pharmacokinetic values could be seen at all skin depths and, also, between perfused non-perfused skin ears. This technique facilitates the direct observation of drug uptake into the skin layers, shedding light on the mechanisms of drug kinetics into the skin.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Novel Model and Screening Tools for Drug Development
Pancreatic ductal adenocarcinomas (PDACs) are often treatment resistant, and as such widefield imaging methods for the evaluation of ECM composition are needed. Here we present a method to measure the relative abundance of ECM diffracting components in PDAC samples alongside drug penetration in widefield images. Orthotopic mouse PDAC xenografts are grown and assessment of drug penetration as well as ECM composition is done using co-registration of scanning x-ray diffraction (XRD) and EGFR-specific drug penetration fluorescent widefield images. Preliminary data suggests a strongly negative correlation between abundance of diffracting ECM components and penetration of large drugs in solid tumors. This methodology may be used to provide crucial insights into both drug-development approaches and multi-therapeutic treatment strategies in late stage PDAC patients presenting with ECM desmoplasia.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Understanding skin drug diffusion under in use conditions is a prerequisite to building accurate and predictive mathematical models. Non-invasive microscopic techniques, combined with use of an epidermal model that retains viability without destroying and disrupting the biological, metabolic, chemical and enzymatic properties of the skin can enable in vitro characterisation of molecular diffusion without the need for in vivo experiments. We studied drug diffusion in the presence and absence of transport inhibitors, to highlight the significance of the right in vitro models, while making key observations of diffusion kinetics and cellular transport.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Our goal is to accelerate pre-clinical drug discovery by developing novel imaging assays to screen and optimize the delivery of targeted anti-cancer drugs. Fluorescence lifetime imaging (FLI) Forster Resonance Energy Transfer (FRET) acts as a direct reporter of drug-target engagement in live mice carrying HER2-overexpressing tumor xenografts. We have established near-infrared (NIR) Macroscopy FLI FRET (MFLI-FRET) non-invasive imaging approach to measure drug-target engagement in deep tissues. We used trastuzumab (TZM), an anti-HER2 antibody clinical drug, as NIR-labeled FRET probes to assess quantitatively the role of tumor microenvironment on drug-target binding and penetration in tumor xenografts.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Stimulated Raman scattering (SRS) offers high sensitivity to monitor low-concentration drugs in real time. However, the "needle" of a drug signal at millimolar concentrations is hidden in the "haystack" of tissue background Raman signals, which practically limits the specificity of the drug measurements. Here, we compare two promising solutions, namely frequency-modulated SRS (FM-SRS) and time-resolved phase-modulated SRS (PM-SRS). We show that the temporal response of FM-SRS is a simple sinusoidal function and its specificity must be compromised. However, the time-resolved PM-SRS with shaped probe pulses provides temporal high-pass filtering with steep cutoff characteristics, enabling higher specificity in the drug measurement.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Time-domain mesoscopic fluorescence molecular tomography (TD-MFMT) provides a unique window for non-invasively monitoring drug delivery efficacy parameters in targeted anticancer research, such as drug-receptor engagement and intra-tumoral heterogeneity. We investigate the potential of TD-MFMT for ex vivo assessment of Trastuzumab-HER2 target engagement and drug distribution in two types of breast and ovarian cancer tumor xenograft models (AU565 and SK-OV-3) via lifetime FRET technique. FRET fraction level and fluorescence drug distribution results reveal that drug accumulation within tumors cannot be automatically associated with targeted cellular drug delivery.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
In recent years, stimulated Raman Scattering (SRS) microscopy has emerged as an important tool for drug imaging. By tuning to the vibrational frequency of chemical bonds within a drug’s native structure, label-free imaging can often be achieved, allowing investigation of drug pharmacokinetics, metabolism and biodistribution. However, with ca. 95% of FDA-approved drugs lacking a suitable Raman-active moiety, the development of small, highly Raman-active tags is essential to take full advantage of the technique in drug imaging. Moreover, currently available Raman tags, such as the widely known bisaryl butadiyne (BADY) tag and other polyyne tags, are not optimised for tracking small biomolecules, primarily due to poor solubility and laborious, expensive syntheses. We have considered the physicochemical properties of tag candidates to design and synthesise improved BADY analogues. The new BADY tags were attached to the PARP inhibitor olaparib, revealing information on biodistribution by Raman spectroscopy for the first time. Differences in the subcellular localisation of the compounds were correlated with experimentally determined predictors of drug-likeness such as polar surface area (PSA) and log D. Studies to determine the extent of drug-target engagement were carried out using both SRS and fluorescence-based techniques, which will inform future tag design and provide vital information on drug action in cells.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Immune checkpoint inhibitors (ICIs) are among the most effective classes of cancer immunotherapies yet only a small minority of patients derive clinical benefit. We are investigating the use of multi-spectral paired-agent imaging (mPAI) to quantify available PD-1 and PD-L1 receptor concentrations for the therapeutic binding of anti-PD-1 checkpoint inhibitors.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
This conference presentation was prepared for the Visualizing and Quantifying Drug Distribution in Tissue VII conference at SPIE BiOS, SPIE Photonics West 2023.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
Publisher's Note: This paper, originally published on 14 March 2023, was replaced with a corrected/revised version on 26 June 2023. If you downloaded the original PDF but are unable to access the revision, please contact SPIE Digital Library Customer Service for assistance.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.