Education & Certifications
PhD, CUDIM - UdelaR, PET 11C Radiochemistry
MSc, UdelaR - College of Chemistry, Medicinal / Pharmaceutical Chemistry
BS, UdelaR - College of Chemistry, Chemistry
The β-amyloid radiotracer [11C] PiB is extensively used for the Positron Emission Tomography (PET) diagnosis of Alzheimer's Disease and related dementias. For clinical use, [11C] PiB is produced using the 11C-methylation method ([11C] Methyl iodide or [11C] methyl triflate as 11C-methylation agents), which represents the most employed 11C-labelling strategy for the synthesis of 11C-radiopharmaceuticals. Recently, the use of direct [11C]CO2 fixation for the syntheses of 11C-tracers has gained interest in the radiochemical community due to its importance in terms of radiochemical versatility and for permitting the direct employment of the cyclotron-produced precursor [11C]CO2. This paper presents an optimised alternative one-pot methodology of [11C]CO2 fixation-reduction for the rapid synthesis of [11C] PiB using an automated commercial platform and its quality control.[11C] PiB was obtained from a (25.9 ± 13.2)% (Average ± Variation Coefficient, n = 3) (end of synthesis, decay corrected) radiochemical yield from trapped [11C]CO2 after 1 min of labelling time using PhSiH3 / TBAF as the fixation-reduction system in Diglyme at 150 °C. The radiochemical purity was higher than 95% in all cases, and the molar activity was (61.4 ± 1.6) GBq/μmol. The radiochemical yield and activity (EOS) of formulated [11C] PiB from cyclotron-produced [11C]CO2 was (14.8 ± 12.1)%, decay corrected) and 9.88 GBq (± 6.0%), respectively. These are higher values compared to that of the 11C-methylation method with [11C]CH3OTf (~ 8.3%).The viability of the system PhSiH3 / TBAF to efficiently promote the radiosynthesis of [11C] PiB via direct [11C]CO2 fixation-reduction has been demonstrated. [11C] PiB was obtained through a fully automated radiosynthesis with a satisfactory yield, purity and molar activity. According to the results, the one-pot methodology employed could reliably yield sufficiently high tracer amounts for preclinical and clinical use.
View details for DOI 10.1186/s41181-019-0065-4
View details for PubMedID 31659494
View details for PubMedCentralID PMC6635575
The synthesis of [11C]L-deprenyl-D2 for imaging of astrocytosis with positron emission tomography (PET) in neurodegenerative diseases has been previously reported. [11C]L-deprenyl-D2 radiosynthesis requires a precursor, L-nordeprenyl-D2, which has been previously synthesized from L-amphetamine as starting material with low overall yields. Here, we present an efficient synthesis of L-nordeprenyl-D2 organic precursor as free base and automated radiosynthesis of [11C]L-deprenyl-D2 for PET imaging of astrocytosis. The L-nordeprenyl-D2 precursor was synthesized from the easily commercial available and cheap reagent L-phenylalanine in five steps. Next, N-alkylation of L-nordeprenyl-D2 free base with [11C]MeOTf was optimized using the automated commercial platform GE TRACERlab® FX C Pro.A simple and efficient synthesis of L-nordeprenyl-D2 precursor of [11C]L-deprenyl-D2 as free base has been developed in five synthetic steps with an overall yield of 33%. The precursor as free base has been stable for 9 months stored at low temperature (-20 °C). The labelled product was obtained with 44 ± 13% (n = 12) (end of synthesis, decay corrected) radiochemical yield from [11C]MeI after 35 min synthesis time. The radiochemical purity was over 99% in all cases and specific activity was (170 ± 116) GBq/μmol.A high-yield synthesis of [11C]L-deprenyl-D2 has been achieved with high purity and specific activity. L-nordeprenyl-D2 precursor as free amine was applicable for automated production in a commercial synthesis module for preclinical and clinical application.
View details for DOI 10.1186/s41181-017-0029-5
View details for PubMedID 29503851
View details for PubMedCentralID PMC5824701
Two (11)C-labelled PET tracers, (R)-N-[(11)C]methyl-N-(3,3-dideuteropropargyl)-1-phenylpropan-2-amine ([(11)C]L-deprenyl-D2, [(11)C]DED) and (S)-N-[(11)C]methyl-N-propargyl-1-phenylpropan-2-amine ([(11)C]D-deprenyl, [(11)C]DDE) were synthesised. One step N-alkylation with [(11)C]MeI or [(11)C]MeOTf was performed using the automated platform TRACERlab® FX-C Pro. The labelled products were obtained with (37±15)% (n=10) (end of synthesis, decay corrected from [(11)C]MeI) radiochemical yields from [(11)C]MeI after 38±3min synthesis time. In all cases, radiochemical purity was over 99% when [(11)C]MeOTf was used. This synthesis using a commercial platform makes these tracers more accessible for clinical research purposes.
View details for DOI 10.1016/j.apradiso.2015.12.051
View details for Web of Science ID 000372380900006
View details for PubMedID 26760951
A series of new 3-alkoxy- or 3-hydroxy-1-[omega-(dialkylamino)alkyl]-5-nitroindazoles have been synthesized and their trichomonacidal, antichagasic and antineoplastic properties studied. Five derivatives (5, 6, 8, 9 and 17) showed remarkable trichomonacidal activity against Trichomonas vaginalis at 10 microg/mL concentration. Three compounds (8, 10, 11) exhibited interesting antichagasic activity and these same compounds moderate antineoplastic activity against TK-10 and HT-29 cell lines. Unspecific cytotoxicity against macrophages has also been evaluated and only compounds 9, 10 and 11 resulted cytotoxic at the higher dose evaluated (100 microg/mL), loosing cytotoxicity at lower doses. QSAR studies have been carried out. X-ray crystallographic study of compound 8 has been performed.
View details for DOI 10.1016/j.bmc.2005.02.043
View details for Web of Science ID 000228612100012
View details for PubMedID 15809155
View details for DOI 10.1016/S0040-4039(01)01298-9
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