Multimodal imaging of capsid and cargo reveals differential brain targeting and liver detargeting of systemically-administered AAVs.

The development of gene delivery vehicles with high organ specificity when administered systemically is a critical goal for gene therapy. We combine optical and positron emission tomography (PET) imaging of 1) reporter genes and 2) capsid tags to assess the temporal and spatial distribution and transduction of adeno-associated viruses (AAVs). AAV9 and two engineered AAV vectors (PHP.

Radiosynthesis and initial preclinical evaluation of [C]AZD1283 as a potential P2Y12R PET radiotracer.

Intro: Chronic neuroinflammation and microglial dysfunction are key features of many neurological diseases, including Alzheimer's Disease and multiple sclerosis. While there is unfortunately a dearth of highly selective molecular imaging biomarkers/probes for studying microglia in vivo, P2Y12R has emerged as an attractive candidate PET biomarker being explored for this purpose. Importantly, P2Y12R is selectively expressed on microglia in the CNS and undergoes dynamic changes in expression according to inflammatory context (e.

A Clinical PET Imaging Tracer ([F]DASA-23) to Monitor Pyruvate Kinase M2-Induced Glycolytic Reprogramming in Glioblastoma.

Purpose: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM.

Fully-automated radiosynthesis of the amyloid tracer [C] PiB via direct [C]CO fixation-reduction.

Background: The β-amyloid radiotracer [C] PiB is extensively used for the Positron Emission Tomography (PET) diagnosis of Alzheimer's Disease and related dementias. For clinical use, [C] PiB is produced using the C-methylation method ([C] Methyl iodide or [C] methyl triflate as C-methylation agents), which represents the most employed C-labelling strategy for the synthesis of C-radiopharmaceuticals. Recently, the use of direct [C]CO fixation for the syntheses of C-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 [C]CO.

An efficient preparation of labelling precursor of [C]L-deprenyl-D and automated radiosynthesis.

Background: The synthesis of [C]L-deprenyl-D for imaging of astrocytosis with positron emission tomography (PET) in neurodegenerative diseases has been previously reported. [C]L-deprenyl-D radiosynthesis requires a precursor, L-nordeprenyl-D, which has been previously synthesized from L-amphetamine as starting material with low overall yields. Here, we present an efficient synthesis of L-nordeprenyl-D organic precursor as free base and automated radiosynthesis of [C]L-deprenyl-D for PET imaging of astrocytosis.

Automated radiosynthesis of [(11)C]L-deprenyl-D2 and [(11)C]D-deprenyl using a commercial platform.

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.

Synthesis and biological properties of new 5-nitroindazole derivatives.

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.