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  • Journal article
    Yue TTC, Ge Y, Aprile FA, Ma MT, Pham TT, Long NJet al., 2023,

    Site-Specific 68Ga Radiolabeling of Trastuzumab Fab via Methionine for ImmunoPET Imaging.

    , Bioconjug Chem

    Bioconjugates of antibodies and their derivatives radiolabeled with β+-emitting radionuclides can be utilized for diagnostic PET imaging. Site-specific attachment of radioactive cargo to antibody delivery vectors provides homogeneous, well-defined immunoconjugates. Recent studies have demonstrated the utility of oxaziridine chemistry for site-specific labeling of methionine residues. Herein, we applied this approach to site-specifically radiolabel trastuzumab-derived Fab immunoconjugates with 68Ga, which can be used for in vivo PET imaging of HER2-positive breast cancer tumors. Initially, a reactive azide was introduced to a single solvent-accessible methionine residue in both the wild-type Fab and an engineered derivative containing methionine residue M74, utilizing the principles of oxaziridine chemistry. Subsequently, these conjugates were functionalized with a modified DFO chelator incorporating dibenzocyclooctyne. The resulting DFO-WT and DFO-M74 conjugates were radiolabeled with generator-produced [68Ga]Ga3+, to yield the novel PET radiotracers, [68Ga]Ga-DFO-WT and [68Ga]Ga-DFO-M74. In vitro and in vivo studies demonstrated that [68Ga]Ga-DFO-M74 exhibited a higher affinity for HER2 receptors. Biodistribution studies in mice bearing orthotopic HER2-positive breast tumors revealed a higher uptake of [68Ga]Ga-DFO-M74 in the tumor tissue, accompanied by rapid renal clearance, enabling clear delineation of tumors using PET imaging. Conversely, [68Ga]Ga-DFO-WT exhibited lower uptake and inferior image contrast compared to [68Ga]Ga-DFO-M74. Overall, the results demonstrate that the highly facile methionine-oxaziridine modification approach can be simply applied to the synthesis of stable and site-specifically modified radiolabeled antibody-chelator conjugates with favorable pharmacokinetics for PET imaging.

  • Journal article
    Aboagye E, Teh JH, Amgheib A, Fu R, Barnes C, Abrahams J, Ashek A, Wang N, Yang Z, Mansoorudeen M, Long NJ, Aboagye Eet al., 2023,

    Evaluation of [18F]AlF-EMP-105 for molecular imaging of 2 C-Met

    , Pharmaceutics, Vol: 15, Pages: 1-13, ISSN: 1999-4923

    C-Met is a receptor tyrosine kinase that is overexpressed in a range of different cancer types, and has been identified as a potential biomarker for cancer imaging and therapy. Previously, a 68Ga-labelled peptide, [68Ga]Ga-EMP-100, has shown promise for imaging c-Met in renal cell carcinoma in humans. Herein, we report the synthesis and preliminary biological evaluation of an [18F]AlF-labelled analogue, [18F]AlF-EMP-105, for c-Met imaging by positron emission tomography. EMP-105 was radiolabelled using the aluminium-[18F]fluoride method with 46 ± 2% RCY and >95% RCP in 35–40 min. In vitro evaluation showed that [18F]AlF-EMP-105 has a high specificity for c-Met-expressing cells. Radioactive metabolite analysis at 5 and 30 min post-injection revealed that [18F]AlF-EMP-105 has good blood stability, but undergoes transformation—transchelation, defluorination or demetallation—in the liver and kidneys. PET imaging in non-tumour-bearing mice showed high radioactive accumulation in the kidneys, bladder and urine, demonstrating that the tracer is cleared predominantly as [18F]fluoride by the renal system. With its high specificity for c-Met expressing cells, [18F]AlF-EMP-105 shows promise as a potential diagnostic tool for imaging cancer.

  • Journal article
    Lim Kee Chang W, Chan T, Raguseo F, Mishra A, Chattenton D, de Rosales RTM, Long N, Morse Set al., 2023,

    Rapid short-pulses of focused ultrasound and microbubbles deliver a range of agent sizes to the brain

    , Scientific Reports, Vol: 13, ISSN: 2045-2322

    Focused ultrasound and microbubbles can non-invasively and locally deliver therapeutics and imaging agents across the blood–brain barrier. Uniform treatment and minimal adverse bioeffects are critical to achieve reliable doses and enable safe routine use of this technique. Towards these aims, we have previously designed a rapid short-pulse ultrasound sequence and used it to deliver a 3 kDa model agent to mouse brains. We observed a homogeneous distribution in delivery and blood–brain barrier closing within 10 min. However, many therapeutics and imaging agents are larger than 3 kDa, such as antibody fragments and antisense oligonucleotides. Here, we evaluate the feasibility of using rapid short-pulses to deliver higher-molecular-weight model agents. 3, 10 and 70 kDa dextrans were successfully delivered to mouse brains, with decreasing doses and more heterogeneous distributions with increasing agent size. Minimal extravasation of endogenous albumin (66.5 kDa) was observed, while immunoglobulin (~ 150 kDa) and PEGylated liposomes (97.9 nm) were not detected. This study indicates that rapid short-pulses are versatile and, at an acoustic pressure of 0.35 MPa, can deliver therapeutics and imaging agents of sizes up to a hydrodynamic diameter between 8 nm (70 kDa dextran) and 11 nm (immunoglobulin). Increasing the acoustic pressure can extend the use of rapid short-pulses to deliver agents beyond this threshold, with little compromise on safety. This study demonstrates the potential for deliveries of higher-molecular-weight therapeutics and imaging agents using rapid short-pulses.

  • Journal article
    Hamill JM, Ismael A, Al-Jobory A, Bennett TLR, Alshahrani M, Wang X, Akers-Douglas M, Wilkinson LA, Robinson BJ, Long NJ, Lambert C, Albrecht Tet al., 2023,

    Quantum Interference and Contact Effects in the Thermoelectric Performance of Anthracene-Based Molecules.

    , J Phys Chem C Nanomater Interfaces, Vol: 127, Pages: 7484-7491, ISSN: 1932-7447

    We report on the single-molecule electronic and thermoelectric properties of strategically chosen anthracene-based molecules with anchor groups capable of binding to noble metal substrates, such as gold and platinum. Specifically, we study the effect of different anchor groups, as well as quantum interference, on the electric conductance and the thermopower of gold/single-molecule/gold junctions and generally find good agreement between theory and experiments. All molecular junctions display transport characteristics consistent with coherent transport and a Fermi alignment approximately in the middle of the highest occupied molecular orbital/lowest unoccupied molecular orbital gap. Single-molecule results are in agreement with previously reported thin-film data, further supporting the notion that molecular design considerations may be translated from the single- to many-molecule devices. For combinations of anchor groups where one binds significantly more strongly to the electrodes than the other, the stronger anchor group appears to dominate the thermoelectric behavior of the molecular junction. For other combinations, the choice of electrode material can determine the sign and magnitude of the thermopower. This finding has important implications for the design of thermoelectric generator devices, where both n- and p-type conductors are required for thermoelectric current generation.

  • Journal article
    Long NJ, Bhargava S, 2022,

    Professor Edward Abel, FRSC, CBE (1931-2021)

    , DALTON TRANSACTIONS, Vol: 51, Pages: 16781-16783, ISSN: 1477-9226
  • Journal article
    Cooper SM, Siakalli C, White AJP, Frei A, Miller PW, Long NJet al., 2022,

    Synthesis and anti-microbial activity of a new series of bis(diphosphine) rhenium(v) dioxo complexes

    , DALTON TRANSACTIONS, Vol: 51, Pages: 12791-12795, ISSN: 1477-9226
  • Journal article
    Wilkinson LA, Bennett TLR, Grace IM, Hamill J, Wang X, Au-Yong S, Ismael A, Jarvis SP, Hou S, Albrecht T, Cohen LF, Lambert C, Robinson BJ, Long NJet al., 2022,

    Assembly, structure and thermoelectric properties of 1,1 '-dialkynylferrocene 'hinges'

    , CHEMICAL SCIENCE, ISSN: 2041-6520
  • Journal article
    Frei A, Rigby A, Yue TTC, Firth G, Ma MT, Long NJet al., 2022,

    To chelate thallium(i) - synthesis and evaluation of Kryptofix-based chelators for Tl-201

    , DALTON TRANSACTIONS, Vol: 51, Pages: 9039-9048, ISSN: 1477-9226
  • Journal article
    Cooper SM, White AJP, Eykyn TR, Ma MT, Miller PW, Long NJet al., 2022,

    N-Centered Tripodal Phosphine Re(V) and Tc(V) Oxo Complexes: Revisiting a [3+2] Mixed-Ligand Approach

    , INORGANIC CHEMISTRY, Vol: 61, Pages: 8000-8014, ISSN: 0020-1669
  • Journal article
    Li Z, Li B, Wu X, Sheppard SA, Zhang S, Gao D, Long NJ, Zhu Zet al., 2022,

    Organometallic-functionalized interfaces for highly efficient inverted perovskite solar cells

    , SCIENCE, Vol: 376, Pages: 416-+, ISSN: 0036-8075
  • Journal article
    Bennett TLR, Alshammari M, Au-Yong S, Almutlg A, Wang X, Wilkinson LA, Albrecht T, Jarvis SP, Cohen LF, Ismael A, Lambert CJ, Robinson BJ, Long NJet al., 2022,

    Multi-component self-assembled molecular-electronic films: towards new high-performance thermoelectric systems

    , CHEMICAL SCIENCE, Vol: 13, Pages: 5176-5185, ISSN: 2041-6520
  • Journal article
    Sheppard SA, Bennett TLR, Long NJ, 2022,

    Development and Characterisation of Highly Conjugated Functionalised Ferrocenylene Macrocycles

  • Journal article
    Bourke S, Urbano L, Midson MM, Olona A, Qazi-Choudhry B, Panamarova M, Valderrama F, Long NJ, Dailey L-A, Green Met al., 2022,

    Nearly monodispersed, emission-tuneable conjugated polymer nanoparticles

    , Sensors & Diagnostics, Vol: 1, Pages: 1185-1188

    <jats:p>We describe the synthesis of monodispersed, silica encapsulated conjugated polymer nanoparticles, their colour tunability and use in imaging HeLa cells.</jats:p>

  • Journal article
    Braga M, Leow CH, Gil JH, Teh JH, Carroll L, Long NJ, Tang M-X, Aboagye EOet al., 2021,

    Investigating CXCR4 expression of tumor cells and the vascular compartment: A multimodal approach

    , PLoS One, Vol: 16, Pages: 1-21, ISSN: 1932-6203

    The C-X-C chemokine receptor 4 (CXCR4) is G protein-coupled receptor that upon binding to its cognate ligand, can lead to tumor progression. Several CXCR4-targeted therapies are currently under investigation, and with it comes the need for imaging agents capable of accurate depiction of CXCR4 for therapeutic stratification and monitoring. PET agents enjoy the most success, but more cost-effective and radiation-free approaches such as ultrasound (US) imaging could represent an attractive alternative. In this work, we developed a targeted microbubble (MB) for imaging of vascular CXCR4 expression in cancer. A CXCR4-targeted MB was developed through incorporation of the T140 peptide into the MB shell. Binding properties of the T140-MB and control, non-targeted MB (NT-MB) were evaluated in MDA-MB-231 cells where CXCR4 expression was knocked-down (via shRNA) through optical imaging, and in the lymphoma tumor models U2932 and SuDHL8 (high and low CXCR4 expression, respectively) by US imaging. PET imaging of [18F]MCFB, a tumor-penetrating CXCR4-targeted small molecule, was used to provide whole-tumor CXCR4 readouts. CXCR4 expression and microvessel density were performed by immunohistochemistry analysis and western blot. T140-MB were formed with similar properties to NT-MB and accumulated sensitively and specifically in cells according to their CXCR4 expression. In NOD SCID mice, T140-MB persisted longer in tumors than NT-MB, indicative of target interaction, but showed no difference between U2932 and SuDHL8. In contrast, PET imaging with [18F]MCFB showed a marked difference in tumor uptake at 40–60 min post-injection between the two tumor models (p<0.05). Ex vivo analysis revealed that the large differences in CXCR4 expression between the two models are not reflected in the vascular compartment, where the MB are restricted; in fact, microvessel density and CXCR4 expression in the vasculature was comparable between U2932 and SuDHL8 tumors. In conclusion, we success

  • Journal article
    Baker CA, Romain C, Long NJ, 2021,

    Cation-pi interactions enabling hard/soft Ti/Ag heterobimetallic cooperativity in lactide ring-opening polymerisation

    , CHEMICAL COMMUNICATIONS, Vol: 57, Pages: 12524-12527, ISSN: 1359-7345

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