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(1 - 3 of 3)
- Title
- IDENTIFYING OPTIMAL KINETIC PARAMETERS IN QUANTITATIVE PAIRED-AGENT MOLECULAR IMAGING BY APPLYING COMPUTATIONAL BIOLOGY TECHNIQUES
- Creator
- Rangnekar, Aakanksha
- Date
- 2016, 2016-05
- Description
-
Accurate and sensitive discrimination of cancerous tissue from the healthy tissue has been a difficult problem to deal with, resulting in the...
Show moreAccurate and sensitive discrimination of cancerous tissue from the healthy tissue has been a difficult problem to deal with, resulting in the incomplete resection of cancerous tissue and giving rise to ‘call-back’ surgery. Fluorescence guided surgery, which employs a fluorescent imaging agent to highlight key molecular differences between cancerous and healthy tissue is a promising approach for improving cancer discrimination during tumor resection surgery. However, conventional fluorescence guided surgery methods have not been optimized in terms of maximizing the contrast of cancer to healthy tissue and nonspecific sources of contrast in images can potentially obfuscate the reliability of such approaches, typically owing to variable vascular permeability and retention kinetics of fluorescent imaging agents in cancerous tissues. Paired-agent approaches have been proposed to account for these nonspecific factors. The approaches employ co-administration of a control (untargeted) imaging agent with a cancer targeted imaging agents, the measured signal of which is used to “normalize” out nonspecific components of targeted agent distribution so that the highest possible contrast between cancer and healthy tissue can be realized. This thesis explores how tumor contrast can be optimized by a ratiometric application of paired-agent imaging approach depending on pharmacokinetic characteristics of the targeted and control imaging-agents used. Overall, two parameters were found to be of upmost importance: 1) the plasma elimination half-life of the imaging agents should be long or large compared to the tissue efflux rate, k2, ideally > 10 h for typical k2 levels; 2) the efflux rate of the imaging agents from the extracellular space to the intravascular space needs to be relatively high in the range of 0.05-0.13 min-1. This thesis also highlights the importance of the appropriate imaging time while quantifying the cell surface receptors. With the use of simulations and animal models this thesis identifies the use of kinetic parameters playing a role in the paired-agent imaging approach. By making use of the paired-agent imaging approach in the fluorescence guided surgery it would be possible to accurately quantify the cancer cell surface receptors to optimize identification of the cancerous tissue from the healthy tissue.
M.S. in Biomedical Engineering, May 2016
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- Title
- Non-invasive quantification of cancer drug targets: Mathematical models for paired-agent molecular imaging
- Creator
- Sadeghipour, Negar
- Date
- 2017
- Description
-
Cancer is among the leading causes of death worldwide. Incidence of cancer is rising at a rate that is almost completely nullifying...
Show moreCancer is among the leading causes of death worldwide. Incidence of cancer is rising at a rate that is almost completely nullifying improvements in cancer treatment and the heterogeneity of advanced disease poses significant complications for the development of effective therapies. With more aggressive cancers tending to display abnormally high expression of signaling receptors associated cell proliferation - receptors that tend to be expressed at very low levels by healthy cells in adulthood - many new cancer-specific “molecular therapies” have been developed to target and block these pathways. However, not all cancers overexpress the same proliferation pathways, so many have proposed molecular imaging as a non-invasive means of identifying on a patient-by-patient basis, which specific targets may be overexpressed to tailor therapies to the individual (“precision medicine”). The primary goal of this thesis was to develop and validate some of the first non-invasive means of measuring drug-target concentrations prior to therapy and the first measures of drug-target occupancy during therapy to ultimately predict and monitor the efficacy of cancer molecular therapy. All work was founded on paired-agent molecular imaging protocols that employ co-administration of two imaging agents: one agent that is targeted to the biomolecule of interest (e.g. a cell surface signaling receptor that may be overexpressed by a cancer), and a second, “control” (“untargeted”) agent that is as chemically similar to the targeted agent as possible, but that does not bind to the biomolecule of interest. In all paired-agent imaging strategies, the signal from the control agent is used to account for delivery and nonspecific retention effects that can confound the relationship between the targeted imaging agent concentration in a region-of-interest (ROI) and the targeted biomolecule concentration in that ROI.
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- Title
- Ultrasound Image Guided Robot Arm for Targeted Delivery of Therapeutic Drugs and MicroRNA for Cancer Therapy
- Creator
- Nagarajan Parimala, Abishek
- Date
- 2024
- Description
-
Molecular imaging has revolutionized medical diagnostics by providing detailed insights into biological processes at the molecular level...
Show moreMolecular imaging has revolutionized medical diagnostics by providing detailed insights into biological processes at the molecular level within the living subject. Ultrasound Molecular Imaging (USMI) has emerged as a promising diagnostic imaging modality by utilizing targeted contrast agents to unveil crucial molecular information, including vascular biomarkers associated with cancer and other diseases. Despite its potential, the transition of Ultrasound Contrast Agents (UCA) from preclinical evaluation to FDA-approved clinical use faces challenges due to the short in vivo half-life of Micro-Bubbles (MBs), necessitating repeated administrations for comprehensive assessments. Moreover, conventional ultrasound imaging methods suffer from limited scanning areas and single-target focus, leading to low throughput in preclinical evaluations.This thesis addresses these challenges by proposing a robot-assisted whole-body scanning pipeline for preclinical evaluations in Ultrasound Molecular Imaging. By integrating a robotic arm into the imaging setup, this approach enhances scanning flexibility and precision, enabling scans across the entire body of a mouse. This extension of the imaging time window allows for comprehensive assessments without the need for repeated contrast agent administrations. Additionally, the ability to simultaneously scan multiple targets within the same session significantly increases the throughput of preclinical assessments, thereby improving the efficiency and reliability of Ultrasound Molecular Imaging in clinical translation.
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