Justin Bailey

University of Alberta | UAlberta · Department of Oncology

Fluorine-18 (18F) is undoubtedly one of the most frequently applied radionuclides for the development of new radiotracers for positron emission tomography (PET) in the context of clinical cancer, neurological, and metabolic imaging. Until recently, the available radiochemical methodologies to introduce 18F into organic molecules ranging from small-...

Introduction: Trk inhibitors are significant in the realm of personalized medicine as they target specific genetic alterations, such as NTRK gene fusions, leading to improved treatment outcomes for cancer patients. By tailoring the treatment to the genetic characteristics of the tumor rather than the tumor type, Trk inhibitors offer the potential...

Background Tropomyosin receptor kinases (TrkA, TrkB, TrkC) are a family of tyrosine kinases primarily expressed in neuronal cells of the brain. Identification of oncogenic alterations in Trk expression as a driver in multiple tumor types has increased interest in their role in human cancers. Recently, first- and second-generation ¹¹ C and ¹⁸ F-labe...

Abnormal cell surface glycosylation plays a major role in disease processes such as immune evasion. However, the underlying role of glycans is yet to be fully understood. Binding information obtained from glycan arrays can provide critical starting points for downstream applications such as the development of carbohydrate-based inhibitors, vaccines...

Background Tropomyosin receptor kinases (TrkA, TrkB, TrkC) are a family of tyrosine kinases primarily expressed in neuronal cells of the brain. Identification of oncogenic alterations in Trk expression as a driver in multiple tumor types has increased interest in their role in human cancers. Recently, first and second generation ¹¹C and ¹⁸F-labeled...

Phosphodiesterase 5 (PDE5) is a clinically relevant biomarker and therapeutic target for many human pathologies, yet a noninvasive agent for the assessment of PDE5 expression has yet to be realized. Such agents would improve our understanding of the nitric oxide (NO)/cyclic guanosine 3′,5′-monophosphate (cGMP)/PDE5 pathway in human pathologies and...

The incorporation of silicon fluoride acceptor (SiFA) moieties into a variety of molecules, such as peptides, proteins and biologically relevant small molecules, has improved the generation of 18 F-radiopharmaceuticals for medical imaging. The efficient isotopic exchange radiofluorination process, in combination with the enhanced [ 18 F]SiFA in viv...

The central dogma of biology does not allow for the study of glycans using DNA sequencing. We report a liquid glycan array (LiGA) platform comprising a library of DNA ‘barcoded’ M13 virions that display 30–1,500 copies of glycans per phage. A LiGA is synthesized by acylation of the phage pVIII protein with a dibenzocyclooctyne, followed by ligation...

Here, we describe an extension of our silicon fluoride acceptor (SiFA) protocol for ¹⁸F-labeling of peptides that addresses challenges associated with preparing a clinical-grade (Tyr³)-octreotate (TATE) tracer for diagnosis of neuroendocrine tumors (NETs). After several iterations of protocol optimization (e.g., finding the optimal pH at which the...

The three tropomyosin receptor kinases (TrkA, B, and C) fulfill important roles within the central nervous system facilitating neuronal growth, neuronal survival, and neuronal differentiation during cell development at all ages of neuronal development. The downregulation of TrkA, B, and C has been identified as an important hallmark of a plethora o...

Introduction: Tropomyosin receptor kinases (Trks) control processes in the fields of growth, survival and differentiation of neuronal processes. They also play a crucial role in neurodegenerative diseases as well as different types of cancer. Interest in developing Trk inhibitors to target NTRK fusion-driven cancers has escalated in the last decade...

Herein we report an efficient radiolabeling of a 18F‐fluorinated derivative of dual inhibitor GW2580, with its subsequent evaluation as a positron emission tomography (PET) tracer candidate for imaging of two neuroreceptor targets implicated in the pathophysiology of neurodegeneration: tropomyosin receptor kinases (TrkB/C) and colony stimulating fa...

The tropomyosin receptor kinase TrkA/B/C family is responsible for human neuronal growth, survival and differentiation from early nervous system development stages onward. Downregulation of TrkA/B/C receptors characterizes numerous neurological disorders including Alzheimer disease (AD). Abnormally expressed Trk receptors or chimeric Trk fusion pro...

The tropomyosin receptor kinases family (TrkA, TrkB, and TrkC) supports neuronal growth, survival, and differentiation during development, adult life, and aging. TrkA/B/C downregulation is a prominent hallmark of various neurological disorders including Alzheimer’s disease (AD). Abnormally expressed or overexpressed full-length or oncogenic fusion...

Straightforward radiosynthesis protocols for fluorine-18 (18F) labeled radiopharmaceuticals are an indispensable but often overlooked prerequisite to successfully carry out molecular imaging studies in vivo by positron emission tomography (PET). In recent years, thanks to the expansion of the 18F chemical toolbox, structurally diverse and novel cli...

Changes in expression levels and dysfunctional signaling of the TrkA/B/C neurotrophin receptors and oncogenic Trk fusion proteins are found in multiple neurological diseases and cancers. Drug-like small molecules which modulate Trk activity, espe-cially pan-Trk tyrosine kinase inhibitors (TKIs), are currently heavily pursued in the clinic. We have...

Nanoparticles represent the most widely studied drug delivery systems targeting cancer. Polymeric nanoparticles can be easily generated through a microemulsion polymerization. Herein, the synthesis, radiolabeling, and in vivo evaluation of nanoparticles (NPs) functionalized by an organosilicon fluoride acceptor (SiFA) are reported which can be radi...

In this paper we describe the use of Cu-mediated [18F]fluorodeboronation for the automated production of PET radiotracers suitable for clinical use. Two recurrent issues with the method, low radiochemical conversion (RCC) on automation and protoarene byproduct purification issues, have been successfully addressed. The new method was utilized to pro...

The proto-oncogenes NTRK1/2/3 encode the tropomyosin receptor kinases TrkA/B/C which play pivotal roles in neurobiology and cancer. We describe herein the discovery of [¹¹C]-(R)-3 ([¹¹C]-(R)-IPMICF16), a first-in-class positron emission tomography (PET) TrkB/C-targeting radiolabeled kinase inhibitor lead. Relying on extensive human kinome vetting,...

Prosthetic group (PG) applications in ¹⁸F-radiochemistry play a pivotal role among current ¹⁸F⁻labeling techniques for the development and availability of ¹⁸F-labeled imaging probes for PET (Wahl, 2002) (¹). The introduction and popularization of PGs in the mid-80s by pioneers in ¹⁸F-radiochemistry has profoundly changed the landscape of available...

Purpose: Prostate-specific membrane antigen (PSMA) is an important biomarker expressed in the majority of prostate cancers. The favorable positron emission tomography (PET) imaging profile of the PSMA imaging agent 2-(3-(1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentane-dioic acid [18F]DCFPyL in preclinical prostate c...

Introduction: Tropomyosin receptor kinases (TrkA/B/C) play crucial roles in the development and maintenance of the nervous system, and aberrant expression of Trk has been implicated in neurological disorders as well as neural and non-neural neoplasms. Patent activity encompassing Trk inhibitors has grown substantially over the last 6 years, recogn...

Introduction: TrkA/B/C receptor activation supports growth, survival, and differentiation of discrete neuronal populations during development, adult life, and ageing but also plays numerous roles in human disease onset and progression. Trk-specific inhibitors have therapeutic applications in cancer and pain and thus constitute a growing area of int...

Over the last 20 years, intensive investigation and multiple clinical successes targeting protein kinases, mostly for cancer treatment, have identified small molecule kinase inhibitors as a prominent therapeutic class. In the course of those investigations, radiolabeled kinase inhibitors for positron emission tomography (PET) imaging have been synt...

Dysregulation of tropomyosin receptor kinases (TrkA/B/C) expression and signalling is recognized as a hallmark of numerous neurodegenerative diseases including Parkinson's, Huntington's and Alzheimer's disease. TrkA/B/C is known to drive tumorogensis and metastatic potential in a wide range of neurogenic and non-neurogenic human cancers. The develo...

Unorthodox 18F-labeling strategies not employing the formation of a carbon-18F bond are seldom found in radiochemistry. Historically the formation of a boron- or silicon-18F bond has been introduced very early on into the repertoire of labeling chemistries but is without translation into any clinical radiotracer besides inorganic B[18F]F4- for brai...

This paper reports on the first experimental study of the energies of noncovalent fluorine bonding in a protein-ligand complex in the absence of solvent. Arrhenius parameters were measured for the dissociation of gaseous deprotonated ions of complexes of bovine β-lactoglobulin (Lg), a model lipid-binding protein, and four fluorinated analogs of ste...

The oligosaccharides Man4 and Man5, substructures of the high-mannose glycans of HIV glycoprotein gp120, were synthesized with a terminal 1-thiomannopyranose residue. The anomeric thiol can be readily converted to an azidomethyl aglycone through reaction with dichloromethane and displacement with sodium azide. The resulting oligomannans were then c...

Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface β-1, 2-mannotriose [β-(Man)(3)] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glyca...

β-(Man)3-Fba pulsed DC/CFA vaccine induced protective responses in C57BL/6 mice against disseminated candidiasis. (A) Vaccination with β-(Man)3-Fba by the DC/CFA-based approach induced protection against disseminated candidiasis by C. albicans strain 3153A in C57BL/6 mice. Vaccinated mice had a prolonged survival time as compared to control mice th...

The immunoprotective beta-mannan of Candida albicans occurs as part of the cell wall phosphomannan N-linked glycoprotein. This macromolecule is composed of an extended alpha1,6 linked mannopyranan backbone containing alpha1,2 mannopyranan branches, to which beta1,2 mannopyranan epitopes are attached. The synthesis of beta1,2-mannan disaccharides cl...