Authors: K. Makrypidi, C. Kiritsis, I. Roupa, A. Chiotellis, M. Papadopoulos, I. Pirmettis
NCSR “Demokritos”, NKUA-Pharmacy Department, Greece
Background
2-18F-fluoro-deoxyglucose ([18F]FDG) is the most applied radiopharmaceutical for glucose metabolism imaging. It has been used for the in-situ labelling of various bioactive amines employing the Maillard reaction. As [18F]FDG lacks the hydroxyl group at the 2nd position, it undergoes the Maillard reaction without forming the classical Amadori product1.
Aims
Aiming at the development of PET tracers for imaging Epidermal Growth Factor Receptor (EGFR), herein we report on the coupling and radiolabelling of the EGFR tyrosine kinase inhibitor, 6-amino-4-[(3-bromophenyl)amino]quinazoline with FDG.
Methods
The 6-amino-4-[(3-bromophenyl)amino]quinazoline and FDG were synthesized based on existing literature2,3. The Maillard reaction, meaning the amine coupling to FDG, will be performed and the expected fluorine derivative will be characterized. The [18F]FDG derivative will be prepared and identified with co-injection in HPLC, using its non-radioactive analogue as a reference.
Results and Conclusion
The amine precursor, bearing an aromatic amine at 6th position, was obtained in four steps using the 4-hydroxyquinazoline, as starting material. The synthesis of 6-amino-4-[(3-bromophenyl)amino]quinazoline was performed in overall high yield while FDG was synthesized in rather low yield. The results from amine coupling and [18F]FDG radiolabeling will be presented.
References
1. Baranwal A. et al. 18F-Fluorodeoxyglycosylamines: Maillard reaction of 18F-fluorodeoxyglucose with biological amines. J Labelled Comp Radiopharm. 2014; 57(2): 86-91
2. Fernandes C. et al. Rhenium and technetium complexes bearing quinazoline derivatives: progress towards a 99mTc biomarker for EGFR-TK imaging. Dalton Trans. 2008; 3215-3225
3. Kováč P. A short synthesis of 2-deoxy-2-fluoro-D-glucose. Carbohydrate Research. 1986;153: 168-170