All ETDs from UAB

Advisory Committee Chair

Jonathan McConathy

Advisory Committee Members

Yu-Hua Dean Fang

Anna Sorace

Document Type

Thesis

Date of Award

2022

Degree Name by School

Master of Science in Biomedical Engineering (MSBME) School of Engineering

Abstract

Triple-negative breast cancer (TNBC) are identified by their lack of estrogen re-ceptor, progesterone receptor, and overexpression of human epidermal growth factor re-ceptor 2-gene. The glucose analog, 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) is the most often utilized PET tracer for imaging TNBC. The use of FDG for imaging primary and metastatic brain tumors is limited by high FDG uptake in normal brain tissue and some forms of inflammation. Also, MRI brain imaging methods have limitation in determining the differentiation between recurrent malignant and treatment effect. Radiolabeled amino acids (AAs), which have a lower uptake in normal brain and inflammation compared to FDG, can be used to target increased amino acid transport, and altered metabolic pathways in cancer cells. Methods: The PET tracers [18F]MeFAMP, [18F]Fluciclovine, [18F]AFETP and [18F]FDG were compared through small animal PET/CT studies in a mouse model and a human model of breast cancer. The data from the PET imaging experiment analyzed and calculated SUVs (Standardized Uptake Value) and Tumor to Brain and Tumor to Muscle (Background) ratios to evaluate and compare the 18F-labeled amino acid PET tracers. Re-sults: In the 4T1 mouse model, the highest tumor to brain SUV ratio was observed with MeFAMP (7.29 ± 2.3), followed by AFETP (4.98±1.2), Fluciclovine (3.33 ±1.2), and FDG iv (0.88 ±0.4), respectively, and in the PDX BCM3936 model, the highest tumor to brain SUV ratio was observed with AFETP (6.75±2), followed by Fluciclovine (2.92±0.7), MeFAMP (2.64±0.9) and FDG (0.67±0.3), respectively. In the 4T1 mouse model, the high-est tumor to muscle SUV ratio was observed with MeFAMP (3.01± 1.1), followed by AFETP (1.68±0.4), Fluciclovine (1.67 ±0.5), and FDG (1.24 ±0.5), respectively, and in the PDX BCM3936 model, the highest tumor to muscle SUV ratio was observed with MeFAMP (4.24±1.1), followed by FDG (2.34±1.1), AFETP (1.92±0.4), and Fluciclovine (1.12±0.3), respectively. Conclusion: MeFAMP, AFETP, and Fluciclovine have favorable tumor imaging properties in these breast cancer models compared to FDG. The higher Tu-mor to Brain and Tumor to Muscle ratios for the amino acids may be advantageous for imaging brain and extracranial metastases and support further evaluation of these agents in breast cancer.

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Engineering Commons

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