AbstractsBiology & Animal Science

Cancer, a major health issue in the United States, is the second leading cause of death after disease of heart. The formation of new blood vessels, known as angiogenesis, which new capillaries sprout from the existing vessels, is believed to promote the tumor growth. Due to the dependence of tumor progression on angiogenesis, it has been an interesting field in the search of antiangiogenesis agents which stop the progression of tumor formation and also different types of receptors accounting for angiogenesis by the ever-evolving positron emission tomography (PET) technology. Phospholipids oxidation in biological systems contributes to diverse pathological processes and is also believed to introduce age-related diseases. Oxidative cleavage of phospholipids containing docosahexaenoic acid (DHA) yields the reactive electrophilic species such as 4-hydroxy-7-oxohept-enoates (HOHA) which would later on covalently bond to e-amino group of protein lysine residue and turn into the 2-(¿-carboxyethyl)pyrrole (CEP) protein adducts. The CEP adducts is found to be associated with age-related macular degeneration (AMD) by triggering the angiogenesis in the retina. Recent study also revealed the novel molecular pattern between CEP adducts and Toll-like receptor 2 (TLR2) which leads to the angiogenesis response. And it provides an alternative therapeutic target especially in cases cancers resistant to the conventional anti-VEGF therapy. Therefore it is necessary to synthesize the gamma radioactive isotope labeled CEP adducts and apply them for the targeting of TLR2 with PET imaging technique. A convenient synthesis of putative fluorine-18-labeled-CEP was achieved with satisfied yields and the fluorination condition was optimized as well because limited half-life of fluorine-18 (109.7min) required the reaction to be accomplished in a short time-frame. Meanwhile in order to overcome the limited stability of CEP adducts which prevents its long-term usage as standards in immunosorbent assays, their electron-deficient isostere, carboxyethylpyrazoles were synthesized. These synthesized pyrazole compounds showed their similar biological affinity with anti-CEP antibody and were also found to be able to introduce angiogenesis of endothelial cells. Therefore, it provides another approach to the PET imaging of TLR2 expression by incorporating radioactive iodine species.