A5067096111- Neuroblastoma Research and Treatments
- Radiopharmaceutical Chemistry and Applications
- Nanoplatforms for cancer theranostics
- Cancer, Hypoxia, and Metabolism
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Monoclonal and Polyclonal Antibodies Research
- Advanced biosensing and bioanalysis techniques
- Advanced Fluorescence Microscopy Techniques
- Photodynamic Therapy Research Studies
- DNA and Nucleic Acid Chemistry
- Heat shock proteins research
- Medical Imaging Techniques and Applications
- Metal complexes synthesis and properties
- Optical Imaging and Spectroscopy Techniques
- Microtubule and mitosis dynamics
- Galectins and Cancer Biology
- Advanced Fiber Laser Technologies
- Cancer Immunotherapy and Biomarkers
- Adrenal and Paraganglionic Tumors
- Nanoparticle-Based Drug Delivery
- Toxin Mechanisms and Immunotoxins
- Radiomics and Machine Learning in Medical Imaging
- Spaceflight effects on biology
- Ferrocene Chemistry and Applications
Institute of Cancer Research
2016-2023
Institute of Cancer Research
2017-2020
Transnational Press London
2017-2018
Royal Marsden Hospital
2016
Royal Marsden NHS Foundation Trust
2016
The Open University
2006-2014
University of Zurich
2005-2011
Czech Academy of Sciences, Institute of Inorganic Chemistry
2009
University of Warwick
2009
Aptamers are characterized by a rapid renal clearance leading to short in vivo circulating half-life. In order use aptamers as anticancer therapeutic agents, their exposure time the tumor has be enhanced via increasing residency bloodstream. A way achieve this goal is conjugating aptamer poly(ethylene glycol) (PEG). Herein, we present conjugation of bifunctionalized anti-MUC1 (NH(2)-AptA-SR) with (99m)Tc coordinating moiety MAG2 and either conventional branched PEG or comb-shaped PolyPEG...
The human epidermal growth factor receptor 3 (HER3) is overexpressed in several cancers, being linked to a more resistant phenotype and hence leading poor patient prognosis. Imaging HER3 challenging owing the modest number (<50000 receptors/cell) overexpressing cancer cells. Therefore, image vivo, high target affinity PET probes need be developed. This work describes two different [(18)F]AlF radiolabeling strategies of ZHER3:8698 affibody molecule specifically targeting HER3. one-pot...
Abstract Background Surgical resection followed by chemo-radiation postpones glioblastoma (GBM) progression and extends patient survival, but these tumours eventually recur. Multimodal treatment plans combining intraoperative techniques that maximise tumour excision with therapies aiming to remodel the immunologically cold GBM microenvironment could improve patients’ outcomes. Herein, we report targeted photoimmunotherapy (PIT) not only helps define location margins additionally promotes...
The future of <sup>89</sup>Zr-based immuno-PET is reliant upon the development new chelators with improved stability compared to currently used deferoxamine (DFO).
Abstract Fluorescence-guided surgery is set to play a pivotal role in the intraoperative management of pediatric tumors. Shortwave infrared imaging (SWIR) has advantages over conventional near-infrared I (NIR-I) with reduced tissue scattering and autofluorescence. Here, two NIR-I dyes (IRDye800CW IR12), long tails emitting SWIR range, were conjugated clinical-grade anti-GD2 monoclonal antibody (dinutuximab-beta) compare for neuroblastoma surgery. A first-of-its-kind multispectral NIR-I/SWIR...
In head and neck squamous cell cancer, the human epidermal growth factor receptor 1 (EGFR) is dominant signaling molecule among all members of family. So far, cetuximab only approved anti-EGFR monoclonal antibody used for treatment but despite benefits adding it to standard regimens, attempts define a predictive biomarker stratify patients have been unsuccessful. We hypothesized that imaging with EGFR-specific radioligands may facilitate noninvasive measurement EGFR expression across entire...
A large number of applications for fibroblast activation protein inhibitors (FAPI)-based PET agents have been evaluated in conditions ranging from cancer to non-malignant diseases such as myocardial infarction. In particular, 68Ga-FAPI-46 was reported a high specificity and affinity FAP-expressing cells, fast accumulation tumor lesions/injuries together with body clearance when investigated vivo. Due the increasing interest use agent both preclinically clinically, we developed an automated...
There is no established method to assess the PD-L1 expression in brain tumours. Therefore, we investigated suitability of affibody molecule (ZPD-L1) radiolabelled with F-18 (Al18F) and Ga-68 measure xenograft mouse models GBM. Mice bearing subcutaneous orthotopic tumours were imaged 1 h post-radioconjugate administration. Ex vivo biodistribution studies immunohistochemistry (IHC) staining performed. Tumoural CD4+/CD8+ tumour-infiltrating lymphocytes evaluated human GBM specimens. ZPD-L1 was...
Aptamers are known for their short in vivo circulating half-life and rapid renal clearance. Their conjugation to poly(ethylene glycol) (PEG) is a way improve residence the body. Two aptamers (AptD AptF), having disulfide protected thiol modification on 3′ end, have been conjugated maleimide activated PEGs of various molecular weights structures (linear PEG20; branched PEG20 40; PolyPEG17, 40, 60 kDa). The high yield coupling (70−80% most cases) could be achieved using immobilized...
Abstract There is an urgent need to develop therapeutic approaches that can increase the response rate immuno-oncology agents. Photoimmunotherapy has recently been shown generate anti-tumour immunological responses by releasing tumour-associated antigens from ablated tumour cell residues, thereby enhancing antigenicity and adjuvanticity. Here, we investigate feasibility of a novel HER2-targeted affibody-based conjugate (Z HER2:2395 -IR700) selectively induce cancer death in vitro vivo. The...
The first general [<sup>18</sup>F]AIF automated radiolabelling procedure developed on the GE Tracerlab FX FN (Left) and Trasis AllInOne (Right) platforms.
Abstract Purpose: Recent studies have highlighted a role of HER3 in HER2-driven cancers (e.g., breast cancer), implicating the upregulation receptor resistance to HER-targeted therapies and Hsp90 inhibitors AUY922). Therefore, we developed an affibody-based PET radioconjugate that quantitatively assesses changes induced by inhibition vivo. Experimental Design: ZHER3:8698 affibody molecules were conjugated via C-terminus cysteine DFO-maleimide for 89Zr radiolabeling. The probe was...
The new macrocyclic ligand 15-fluoro-15-methyl-1,4,7,10,13-pentaazacyclohexadecan-14,16-dione (2) was synthesised and its crystal structure determined together with the ones of known analogues 2, 15-fluoro-1,4,7,10,13-pentaazacyclohexadecan-14,16-dione (1) 15,15-difluoro-1,4,7,10,13-pentaazacyclohexadecan-14,16-dione (3). binding behaviour all three ligands to copper zinc studied in solid state. They can bind metal centre by either triple coordination (N3) secondary amines or after double...
Site-selective bioconjugation of cysteine-containing peptides and proteins is currently achieved via a maleimide–thiol reaction (Michael addition). When maleimide-functionalized chelators are used the resulting bioconjugates subsequently radiolabeled, instability has been observed both during radiosynthesis post-injection in vivo, reducing radiochemical yield negatively impacting performance. Recently, phenyloxadiazolyl methylsulfone derivative (PODS) was proposed as an alternative to...
RATIONALE The consumption of red meat is known to enhance the endogenous formation N ‐nitroso compounds (NOCs), which are potent carcinogens. DNA damage related NOCs, and hence meat, has been detected in colorectal cells blood. We proposed extend previous studies a non‐invasive approach for detection O 6 ‐carboxymethylguanine (O CMG) ‐carboxymethyl‐2'‐deoxyguanosine CMdG) urine relation intake using liquid chromatography/tandem mass spectrometry (LC/MS/MS). presence adduct samples either as...
In radiopharmaceutical syntheses, maleimide is commonly used for linking thiol-bearing bioactive molecules to metal–complexing ligands (chelators).
Metal ions bind to nucleic acids at various positions. This binding can be modulated by using metal complexes with appropriate ligands. Novel mono- and especially dinuclear could a powerful tool detect rare, but still physiologically relevant, forms of DNA, e.g. the left-handed Z-DNA. In this review, our recent research activities in area bioinorganic chemistry are summarized. A special emphasis is laid on synthetic challenges that arose upon synthesis polyamine Further, some rather unusual...
Automated <sup>18</sup>F-trifluoromethylation provided the first radiosynthesis of [<sup>18</sup>F]Trifluridine, which shows potential as a PET probe drug mechanism action.
X-ray irradiation of plasmid DNA in presence platinum (II)-based compounds was carried out order to assess the radiosensitization capabilities these drugs. In present investigations pBR322 used monitor effectiveness chosen inducing strand breaks. Samples were incubated potential radiosensitisers: (II) bromide and cis-diamminedibromoplatinum (II). The results examined against a common cancer chemotherapy drug cis-diamminedichloroplatinum It found that can greatly increase levels single-...
Background Epidemiological studies have shown that only about 20% of the familial clustering breast cancer is explained by known highly penetrant mutations in BRCA1 and BCRA2.We set out to search for genes remaining 80%.Twin indicate a predominant role shared rather than environment; patterns occurrence families are consistent with major polygenic component.Methods We assembled population based 5,000 cases controls from East Anglian population.We simple clinical epidemiological information,...
The synthesis of a benzooxazol-5-yl acetic acid derivative (9) with strong heparanase and angiogenesis inhibitory activity, thus possible commercial interest, is described in detail.
Accurate quantification in molecular imaging is essential to improve the assessment of novel drugs and compare radiobiological effects therapeutic agents prior in-human studies. The aim this study was investigate challenges feasibility pre-clinical quantitative mouse-specific dosimetry 111In-labelled radiotracers. Attenuation, scatter partial volume were studied using phantom experiments, an activity calibration curve obtained for varying sphere sizes. Six SK-OV-3-tumour bearing mice...
Abstract Background Immune checkpoint inhibitors (ICPIs) have proven to restore adaptive anti-tumor immunity in many cancers; however, no noteworthy therapeutic schedule has been established for patients with glioblastoma (GBM). High programmed death-ligand 1 (PD-L1) expression is associated immunosuppressive and aggressive phenotypes GBM. Presently, there standardized protocol assessing PD-L1 levels select monitor their response ICPI therapy. The aim of this study was investigate the use...