80 research outputs found
Preparation of ¹¹C-Carbonyl Compounds and Radiotracer Validation for Cardiac PET Imaging
No full textMolecular imaging techniques serve an integral role in clinical practice for the diagnosis and prognosis of various morbidities. Positron emission tomography (PET) is an imaging modality employing radiolabelled probes to visualize biochemical processes. Radiochemical synthesis is used to incorporate radioactive isotopes into small molecules or peptides targeting a protein of interest. Access to radiotracers is therefore dependent on the availability of radiochemical methods for the addition of radionuclides. This thesis describes the key steps in the process of developing a new radiotracer, from designing methodologies for their synthesis, to the production and evaluation of a novel probe, and finally the analysis of tracer kinetics in PET imaging. Beginning with Chapter 1, PET and radiochemistry will be introduced.
Chapter 2 is focused on a general methodology to access ¹¹C-amides, using transition metal-catalyzed additions of organozinc iodides to ¹¹C-isocyanates. In the chapter’s central article, [¹¹C]CO₂ produced directly from the cyclotron was captured and converted to reactive ¹¹C-isocyanate electrophiles before being derivatized by aryl and alkyl organozinc iodides. Additional work on the development of alternative ¹¹C-carbonyl compounds is also described.
Chapter 3 presents the radiolabelling of one such ¹¹C-carbonyl, describing the development of a radiotracer based on the selective Rev-erb inhibitor SR9009. Given recently elucidated potential for therapeutic applications of Rev-erb inhibitors like SR9009 in the management of cardiovascular disease, (R)- and (S)-[¹¹C]SR9009 were synthesized for cardiac investigation of circadian biology.
Chapter 4 explores a novel approach to prepare ¹¹C-amino acids with [¹¹C]CO₂ via carbon isotope exchange. In this chapter, α-amino acids are condensed to Schiff bases using aldehydes; this intermediate can then undergo a carboxylation/decarboxylation cycle in which isotopically-labelled carbon (¹¹C, ¹³C, ¹⁴C) is incorporated. The key paper details the optimization of carbon-11 labelling to prepare enantiopure L- and D-¹¹C-amino acids for imaging.
Chapter 5 discusses the pharmacokinetic and metabolic evaluation of [¹⁸F]flubrobenguane (FBBG) in clinical imaging populations to determine radiotracer kinetics. Patients underwent FBBG PET scans to evaluate cardiac denervation. Blood samples were collected and processed to derive vital parameters for image analysis and interpretation. Patient cohorts were statistically compared to evaluate disease-specific differences in the pharmacokinetics of FBBG
ChemInform Abstract: Aziridine‐2‐carboxaldehyde Dimers Undergo Homo‐Ugi 4‐Component‐5‐center Reactions.
No full textFluorine-18-Labeled Fluorescent Dyes for Dual-Mode Molecular Imaging
No full textRecent progress realized in the development of optical imaging (OPI) probes and devices has made this technique more and more affordable for imaging studies and fluorescence-guided surgery procedures. However, this imaging modality still suffers from a low depth of penetration, thus limiting its use to shallow tissues or endoscopy-based procedures. In contrast, positron emission tomography (PET) presents a high depth of penetration and the resulting signal is less attenuated, allowing for imaging in-depth tissues. Thus, association of these imaging techniques has the potential to push back the limits of each single modality. Recently, several research groups have been involved in the development of radiolabeled fluorophores with the aim of affording dual-mode PET/OPI probes used in preclinical imaging studies of diverse pathological conditions such as cancer, Alzheimer’s disease, or cardiovascular diseases. Among all the available PET-active radionuclides, 18F stands out as the most widely used for clinical imaging thanks to its advantageous characteristics (t1/2 = 109.77 min; 97% β+ emitter). This review focuses on the recent efforts in the synthesis and radiofluorination of fluorescent scaffolds such as 4,4-difluoro-4-bora-diazaindacenes (BODIPYs), cyanines, and xanthene derivatives and their use in preclinical imaging studies using both PET and OPI technologies
Gross and histopathologic diagnoses from North Atlantic right whale Eubalaena glacialis mortalities between 2003 and 2018
No full textSeventy mortalities of North Atlantic right whales Eubalaena glacialis (NARW) were documented between 2003 and 2018 from Florida, USA, to the Gulf of St. Lawrence, Canada. These included 30 adults, 14 juveniles, 10 calves, and 16 of unknown age class. Females represented 65.5% (19/29) of known-sex adults. Fourteen cases had photos only; 56 carcasses received external examinations, 44 of which were also necropsied. Cause of death was determined in 43 cases, of which 38 (88.4%) were due to anthropogenic trauma: 22 (57.9%) from entanglement, and 16 (42.1%) from vessel strike. Gross and histopathologic lesions associated with entanglement were often severe and included deep lacerations caused by constricting line wraps around the flippers, flukes, and head/mouth; baleen plate mutilation; chronic extensive bone lesions from impinging line, and traumatic scoliosis resulting in compromised mobility in a calf. Chronically entangled whales were often in poor body condition and had increased cyamid burden, reflecting compromised health. Vessel strike blunt force injuries included skull and vertebral fractures, blubber and muscle contusions, and large blood clots. Propeller-induced wounds often caused extensive damage to blubber, muscle, viscera, and bone. Overall prevalence of NARW entanglement mortalities increased from 21% (1970-2002) to 51% during this study period. This demonstrates that despite mitigation efforts, entanglements and vessel strikes continue to inflict profound physical trauma and suffering on individual NARWs. These cumulative mortalities are also unsustainable at the population level, so urgent and aggressive intervention is needed to end anthropogenic mortality in this critically endangered species
ChemInform Abstract: Comparison of Benzene, Nitrobenzene, and Dinitrobenzene 2‐Arylsulfenylpyrroles.
No full text
Some remarks on stability for a phase-field model with memory
No full textThe phase field system with memory can be viewed as a phenomenological extension of the classical phase equations in which memory effects have been taken into account in both fields. Such memory effects could be important for example during phase transition in polymer melts in the proximity of the glass transition temperature where configurational degrees of freedom in the polymer melt constitute slowly relaxing "internal modes" which are di±cult to model explicitly. They should be relevant in particular to glass-liquid-glass transitions where re-entrance effects have been recently reported [27]. We note that in numerical studies based on sharp interface equations obtained from (PFM), grains have been seen to rotate as they shrink [35, 36]. While further modelling and numerical efforts are now being undertaken, the present manuscript is devoted to strengthening the analytical underpinnings of the model
Facile 18F labeling of non-activated arenes via a spirocyclic iodonium(III) ylide method and its application in the synthesis of the mGluR5 PET radiopharmaceutical [18F]FPEB
No full text- …
