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Title: Towards the Development of Accessible and Biocompatible Porphyrin Nanoparticles for PET Imaging Applications
Authors: Lim, Tristan
Advisors: Prud'homme, Robert K
Department: Chemical and Biological Engineering
Certificate Program: Global Health and Health Policy Program
Class Year: 2018
Abstract: Positron emission tomography (PET) is a biomedical imaging modality that detects gamma rays produced from positron collisions with electrons inside a patient’s body to construct real-time images of molecular processes. Requiring low concentrations of radionuclides on the order of 10\(^{-9}\) to 10\(^{-12}\) moles, PET is orders of magnitude more sensitive than targeted SPECT and MRI systems, leading to its widespread use in cancer diagnosis and treatment assessment. While several PET tracers exist for use in clinical imaging, they are challenged by poor specificity, limited signal production, and short half-lives, which hinder the accessibility and implementation of PET imaging. Current advances in nanomedicine have developed nanoparticle (NP) contrast agents that provide capabilities of active ligand targeting, increased signal intensity by clustering radionuclides, and greater accessibility via chelation of longer half-life radioisotopes; however, these developments are still limited by harsh loading conditions, low loading efficacy, and biocompatibility concerns. Towards this end, this project presents the use of Flash NanoPrecipitation to encapsulate a known copper chelator and FDA-approved hematoporphyrin derivatve (HpD) compound for the development of a biocompatible PET-active NP contrast agent with greater signal intensity, active ligand targeting capabilities, and post-formulation PET activation. Water dispersible polyethylene glycol-coated NPs were formed with >50% weight loading of HpD and sizes ranging from 70 nm to 170 nm. Radiolabeling with copper-64 in a pH 5.5 buffer at 37°C resulted in >99% uptake of the initial 1.1 MBq radioactivity within 15 minutes, and stability tests exhibited NP resistance against additional copper chelators. These results demonstrate rapid and specific copper-64 chelation under mild conditions into biocompatible porphyrin NPs that greatly expands PET imaging applications.
Type of Material: Princeton University Senior Theses
Language: en
Appears in Collections:Global Health and Health Policy Program, 2017-2022
Chemical and Biological Engineering, 1931-2022

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