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. References1. Baranwal A. et al. 18F-Fluorodeoxyglycosylamines: Maillard reaction of 18F-fluorodeoxyglucose with biological amines. J Labelled Comp Radiopharm. 2014; 57(2): 86-912. Fernandes C. et al. Rhenium and technetium complexes bearing quinazoline derivatives: progress towards a 99mTc biomarker for EGFR-TK imaging. Dalton Trans. 2008; 3215-32253. Kováč P. A short synthesis of 2-deoxy-2-fluoro-D-glucose. Carbohydrate Research. 1986;153: 168-170
Authors: Federico Luzi, Antony Gee, Salvatore Bongarzone King’s College London Background Formamides are common motifs of biologically-active compounds (e.g. formoterol, octotiamine, fursaltiamine etc)1 and are frequently employed as intermediates to yield, for example, benzimidazoles.2 A rapid, simple and reliable route to [carbonyl-11C]formamides would enable access to this important class of compounds as in vivo PET imaging agents. Aims We report the rapid, one-pot 11C-formylation of amines via the reduction of [11C]isocyanate intermediates formed directly from cyclotron-produced [11C]CO2. The method was applied to the radiolabelling of a small library of formamides and the chemotactic molecule formyl methionine.
Authors: Biti, A., Fraguas-Sánchez, A.I., & Sarparanta, M. University of Helsinki Background Adoptive cell therapy is a promising mode of cancer therapy employing tumor infiltrating lymphocytes (TILs) with a limited success to hematologic cancers and melanoma.1 Molecular imaging strategies based on bioorthogonal chemistry and metabolic glycoengineering for in vivo tracking of TILs provide advantages compared to conventional techniques.2 Aims The aim of this study is to develop a new radiolabeling method for TILs without impairment of their antitumor and homing properties by using a Staudinger ligation between a perfluoroaryl azide tag3 on the surface of murine OT-I lymphocytes installed by metabolic glycoengineering and novel fluorine-18 radiolabeled phosphine reagents. Methods The PFAA-modified D-mannosamine is synthesized according to a reported procedure. The phosphine reagents present a linker and the NODAGA radiochelator and are synthesized by using common organic reactions. The radiolabeling with [18F]aluminum fluoride (AlF) requires in situ synthesis of [18F]AlF starting from saline-eluted [18F]fluoride ion and aluminum chloride (AlCl3). Results and Conclusion This labeling method eliminates the drying step needed for most [18F]F− labeling methods. Furthermore, Al18F complexes are hydrophilic and can be used for the radiolabeling of sensitive targets such as cells in aqueous systems. This could be a method towards the radiolabeling of TILs without genetic manipulation. References 1. Schietinger, A., et al., Tumor-Specific T Cell Dysfunction Is a Dynamic Antigen-Driven Differentiation Program Initiated Early during Tumorigenesis. Immunity, 2016. 45(2): p. 389-401.2. Rossin, R., et al., Diels–Alder Reaction for Tumor Pretargeting: In Vivo Chemistry Can Boost Tumor Radiation Dose Compared with Directly Labeled Antibody. Journal of Nuclear Medicine, 2013. 54(11): p. 1989-1995.3. Sundhoro, M., et al., Perfluoroaryl Azide Staudinger Reaction: A Fast and Bioorthogonal Reaction. Angewandte Chemie International Edition, 2017. 56(40): p. 12117-12121.
Authors: Francesca Goudoua,b,c, Virginie Hourtaneb, Nicolas Masseb, Yahya Cisseb, Abdul Karim Haji Dheerec and Antony Geec a SYNBIOLAB – Actualis Jarry, 44 rue Henry Becquerel Jarry 97122 Baie-Mahault – Guadeloupe.b PMB Head office – France Route des Michels CD56, La Corneirelle 13790 Peynier – France. c School of Imaging Sciences and Biomedical Engineering, King’s College London, London, SE1 7EH, UK.