Doctor of Philosophy, Imperial College of Science, Technology & Medicine (2016)
Master of Science, Imperial College of Science, Technology & Medicine (2011)
A novel synthesis of 6''-[18 F]-fluoromaltotriose as a PET tracer for imaging bacterial infection.
Journal of labelled compounds & radiopharmaceuticals
The aim of this study was to develop a positron emission tomography (PET) tracer to visualize and monitor therapeutic response to bacterial infections. In our continued efforts to find maltose based PET tracers that can image bacterial infections, we have designed and prepared 6''-[18 F]fluoromaltotriose as a second generation PET imaging tracer targeting the maltodextrin transporter of bacteria. We have developed methods to synthesize 6''-deoxy-6''-[18 F]fluoro-α-D-glucopyranosyl-(1-4)-O-α-D-glucopyranosyl-(1-4)-O-D-glucopyranose (6''-[18 F]-fluoromaltotriose) as a bacterial infection PET imaging agent. 6''-[18 F]fluoromaltotriose was prepared from precursor, 2'',3'',4''-tri-O-acetyl-6''-O-nosyl-α-D-glucopyranosyl-(1-4)-O-2',3',6'-tri-O-acetyl-α-D-glucopyranosyl-(1-4)-1,2,3,6-tetra-O-acetyl-D-glucopyranose (per-O-acetyl-6''-O-nosyl-maltotriose 4). This method utilizes the reaction between precursor 4 and anhydrous [18 F]KF/Kryptofix 2.2.2 in Dimethylformamide (DMF) at 85o C for 10 minutes to yield per-O-acetyl-6''-deoxy-6-'' [18 F]-fluoromaltotriose (7). Successive acidic and basic hydrolysis of the acetyl protecting groups in 7 produced 6''-[18 F]fluoromaltotriose (8). Also, cold 6''- [19 F]fluoromaltotriose was prepared from per-O-acetyl-6''-hydroxymaltotriose via a DAST reaction followed by a basic hydrolysis. A successful synthesis of 6''-[18 F]-fluoromaltotriose has been accomplished in 8±1.2 % radiochemical yield (decay corrected). Total synthesis time was 120 min. Serum stability of 6''-[18 F]fluoromaltotriose at 37o C indicated that 6''-[18 F]-fluoromaltotriose remained intact up to 2 h. In conclusion, we have successfully synthesized 6''-[18 F]-fluoromaltotriose via direct fluorination of an appropriate precursor of a protected maltotriose.
View details for DOI 10.1002/jlcr.3601
View details for PubMedID 29314161
Long-Delay Arterial Spin Labeling Provides More Accurate Cerebral Blood Flow Measurements in Moyamoya Patients: A Simultaneous Positron Emission Tomography/MRI Study.
2017; 48 (9): 2441–49
Arterial spin labeling (ASL) MRI is a promising, noninvasive technique to image cerebral blood flow (CBF) but is difficult to use in cerebrovascular patients with abnormal, long arterial transit times through collateral pathways. To be clinically adopted, ASL must first be optimized and validated against a reference standard in these challenging patient cases.We compared standard-delay ASL (post-label delay=2.025 seconds), multidelay ASL (post-label delay=0.7-3.0 seconds), and long-label long-delay ASL acquisitions (post-label delay=4.0 seconds) against simultaneous [15O]-positron emission tomography (PET) CBF maps in 15 Moyamoya patients on a hybrid PET/MRI scanner. Dynamic susceptibility contrast was performed in each patient to identify areas of mild, moderate, and severe time-to-maximum (Tmax) delays. Relative CBF measurements by each ASL scan in 20 cortical regions were compared with the PET reference standard, and correlations were calculated for areas with moderate and severe Tmax delays.Standard-delay ASL underestimated relative CBF by 20% in areas of severe Tmax delays, particularly in anterior and middle territories commonly affected by Moyamoya disease (P<0.001). Arterial transit times correction by multidelay acquisitions led to improved consistency with PET, but still underestimated CBF in the presence of long transit delays (P=0.02). Long-label long-delay ASL scans showed the strongest correlation relative to PET, and there was no difference in mean relative CBF between the modalities, even in areas of severe delays.Post-label delay times of ≥4 seconds are needed and may be combined with multidelay strategies for robust ASL assessment of CBF in Moyamoya disease.
View details for DOI 10.1161/STROKEAHA.117.017773
View details for PubMedID 28765286
- Carbon-11 Radiolabelling of Organosulfur Compounds: C-11 Synthesis of the Progesterone Receptor Agonist Tanaproget CHEMISTRY-A EUROPEAN JOURNAL 2015; 21 (25): 9034-9038
- Microfluidic Hydrogenation Reactions by using a Channel-Supported Rhodium Catalyst CHEMCATCHEM 2014; 6 (5): 1199-1203