Details

Autor(en) / Beteiligte

• Broder, Brittany Annjean

Titel

Development and Kinetic Analysis of Emerging Positron Emission Tomography Radiotracer Vandium-48-Labeled Vanadyl Acetylacetonate

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2022

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Vanadyl acetylacetonate (VO(acac)2) has shown promise as a magnetic resonance imaging (MRI) agent due to its high selectivity for cancer cells, which could facilitate differentiation of carcinogenesis stages progressing from inflammation to malignant tumor. This is especially vital for types of cancer where inflammation is a recognized component or precursor for tumorigenesis, such as colorectal cancer (CRC) [32]. The novel positron emission tomography (PET) radiotracer vanadium-48-labeled-VO(acac)2 (48VO(acac)2) is a positron-emitting, long-lived (t1/2 = 16 days) chelated compound that could be used for physiological monitoring of relatively long biological processes not feasible with other modalities or using other radiotracers due to the high sensitivity of PET. This radiotracer could not only provide a new method for longitudinal studies and disease monitoring of CRC and other cancers, but also perhaps elucidate the mechanisms of VO(acac)2 compound accumulation in cancer cells. There are currently no methods to synthesize, characterize, or use this radiotracer in the literature.In this work, such methods are developed. The first objective is to Produce 48V using a Compact Medical Cyclotron. Many facilities focused on clinical radiotracer production, such as the IBA 18/9 Cyclone cyclotron used herein, do not have a dedicated solid target system. However, we have modified a simple beamstop to be used as a target holder. Theoretical calculations and Monte Carlo simulations are done to assess the efficacy of this system.With the irradiated target, the next objective is to Establish a New Procedure for the Synthesis of 48VO(acac)2. The target is dissolved and the 48V extracted via column separation, chelated as 48VO(acac)2, and filtered. Methods are developed iteratively for each step of the process. The compound is characterized and synthesis is confirmed by gamma-ray spectroscopy, high performance liquid chromatography (HPLC), and thin layer chromatography (TLC); a new HPLC method specific to VO(acac)2 was developed for this work and compound characterization.Using the synthesized compound, the final objective is to Conduct In Vitro and In Vivo Studies to Model the Kinetics of 48VO(acac)2. Cellular and animal PET imaging studies using colorectal cancer cell lines HCA-7 and HCT-116 are done to obtain cell-uptake and time-activity curves. This data is used for kinetic modelling to obtain a value for tumor distribution volume ratio, a metric of how quickly the radiotracer enters and exits the tissue from the blood.The proposed research will address and tackle these unexplored issues, potentially leading to significant advances in developing a new radiotracer for PET imaging of cancer.