Labelling Optimization of Various Organic Molecules wıth F-18 Usable in PET Scintigraphy
The main goal of this thesis is to optimize F-18 labelling of various organic molecules which are used with PET scintigraphy. For this purpose, fluorination and alkylation reactions were carried out for model compounds, Butanediol ditosylate (BDDT) and Tert-butyl 4-hydroxybenzylcarbamate (HPMA). These molecules were chosen to optimize fluorination and alkylation reactions of [18F] N-succinimidyl 4-[18F] fluorobenzoate ([18F] SFB).
Fluorination reaction of BDDT with F-18 was performed to optimize F-18 drying step and reaction environment. In addition to the same reason, Quaternary methyl ammonium (light QMA) cartridge was optimized by using different chemicals and solvents. Alkylation reaction of HPMA with F-18 FBT was carried out to synthesize F-18 Tert-butyl 4-fluorobutoxybenzylcarbamate (F-18 FBPMA) by using two different bases, NaH and TBA-OH. At the same time, alkylation reaction environment and time were optimized. Moreover, light C18 cartridge study was optimized to purify F-18 FBT. After all of the reactions, thin layer chromatography (TLC) was applied to analysis of radiochemical yield and purity. Also, high performance liquid chromatography (HPLC) was applied to purify labelling compounds.
[18F] SFB synthesize was realized by using fluorination and alkylation reactions with manuel and automatic synthesizer. A high-yielding and rapid lysine labelling of peptides have been observed with the specific labelling agent for amines, N-succinimidyl 4-[18F] fluorobenzoate. Conjugation of the [18F] SFB moiety is selectively achieved through a lysine (Lys) thiol of the peptides with high yield in a short time. For this reason, human serum albumin protein (HSA) was chosen for conjugation with [18F] SFB. HSA has large amount of lysine contents. This specialty is significant for the reaction yield. After the conjugation, thin layer chromatography (TLC) was applied to observe radiochemical purity and yield. As a result of study, manuel synthesis of [18F] SFB was carried out in a short time with high yield and conjugation of HSA was occurred with high radiochemical purity.
SİNANOĞLU Gizem
Danışman : Prof. Dr. Refiye YANARDAĞ
II. Danışman : Yard. Doç. Dr. Sevim TUNALI
Anabilim Dalı : Kimya
Programı : Biyokimya
Mezuniyet Yılı : 2014
Tez Savunma Jürisi : Prof. Dr. Refiye YANARDAĞ
Prof. Dr. Nuriye AKEV
Prof. Dr. Ayşen YARAT
Prof. Dr. Ayşe OGAN
Prof. Dr. Ayşe YUSUFOĞLU
Dostları ilə paylaş: |