¹¹C-acetate as an imaging biomarker of radioresistance in mouse models of non-small cell lung cancer

Curley, Emer (2024) ¹¹C-acetate as an imaging biomarker of radioresistance in mouse models of non-small cell lung cancer. PhD thesis, University of Glasgow.

Abstract

Background:
This thesis uses PET imaging to explore the use of 11C-acetate, a radiotracer that maps fatty acid synthesis, as a predictive imaging biomarker of radioresistance in subcutaneous allografts and Genetically Engineered Mouse Models (GEMMs).

Aims/ Objectives:
The primary aim of this project was to assess whether 11C-acetate PET could be used as an imaging biomarker of radioresistance using LSL-KrasG12D/+ Rosa26-LSLMyc (KMyc) and KrasG12D/+ p53-/- (KP) GEMMs and subcutaneous KP allografts. To ensure that the treatment was accurately delivered treatment verification was undertaken using γH2AX to verify the coverage of subcutaneous and GEMM tumours. A normal tissue study assessing aeration ratio and mean Hounsfield Units (HU) as methods of evaluating radiation induced lung damage was also performed using Cone Beam Computed Tomography (CBCTs) from the SARRP’s onboard scanner.

Methods/Results:
Statistically significant differences were found in the percentage of γH2AX positive nuclei between irradiated and unirradiated tumours in both the GEMM (p=0.0055) and subcutaneous (p=0.0001) groups, indicating that targeted tumours were being irradiated, and a statistically significant correlation between the change in aeration ratio from Week 0 to Week 4 and the survival time was found in the Radiation Induced Lung Damage Study (rs = -0.94868, p (2- tailed) = 0.01385). In the 11C-acetate PET study the KMyc cohort showed a statistically significant correlation between the 11C-acetate SUVMax and the change in longest length (R²=0.8786, p=0.0058).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences > Beatson Institute of Cancer Research
• Funder's Name: Cancer Research UK (CRUK)
• Supervisor's Name: Lewis, Dr. David and Chalmers, Professor Anthony
• Date of Award: 2024
• Depositing User: Theses Team
• Unique ID: glathesis:2024-84569
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 18 Sep 2024 09:43
• Last Modified: 18 Sep 2024 09:55
• Thesis DOI: 10.5525/gla.thesis.84569
• URI: https://theses.gla.ac.uk/id/eprint/84569