Review
Medicine, General & Internal
Pierrick Gouel, Pierre Decazes, Pierre Vera, Isabelle Gardin, Sebastien Thureau, Pierre Bohn
Summary: Tumor hypoxia is a complex and evolving phenomenon both in time and space. Molecular imaging, such as PET and MRI techniques, can be used to study the variations of hypoxia. However, the tracers and techniques used have their own limitations and complexities. Accurate tools for imaging hypoxia are particularly important due to its negative impact on tumor aggressiveness, dissemination, and resistance to treatments.
FRONTIERS IN MEDICINE
(2023)
Article
Chemistry, Inorganic & Nuclear
Daniel F. Earley, Jose Esteban Flores, Amaury Guillou, Jason P. Holland
Summary: In recent years, copper-64 and copper-67 have been considered as a useful theranostic pair in nuclear medicine. This study successfully demonstrates the viability of photochemically induced conjugation methods for the development of copper-based radiotracers for potential applications in diagnostic PET imaging and targeted radionuclide therapy.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Inorganic & Nuclear
Ina Hierlmeier, Amaury Guillou, Daniel F. Earley, Anthony Linden, Jason P. Holland, Mark D. Bartholomae
Summary: In this study, we synthesized and investigated the coordination chemistry of novel copper(II) and zinc(II) complexes using two heterocyclic triazacyclononane(tacn)-based chelators (HNODThia and NODThia-AcNHEt). The modified chelator HNODThia was used to develop a PSMA-based bioconjugate (NODThia-PSMA) and a photoactivatable azamacrocyclic analogue (NODThia-PEG ( 3 ) -ArN ( 3 )) for copper-64 radiopharmaceuticals. The metal-binding chelates showed rapid radiolabeling, stability in human plasma, and successful photoconjugation to albumin and antibodies. These findings have significant implications for the development of stable Cu-64-based radiopharmaceuticals and the future application of Cu-67 in targeted radioimmunotherapy.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Jacob A. Rowan, Stacey E. Rudd, Katherine Ganio, Christopher A. McDevitt, Jonathan M. White, Paul S. Donnelly
Summary: This research investigates the potential of using acyclic tetrapyrrolic 2,2'-bisdipyrrins as ligands to prepare charge-neutral, lipophilic, cell-permeable, redox active complexes with positron-emitting copper-64. The synthesis and characterization of a series of tetrapyrrolic 2,2'-bisdipyrrin copper(II) complexes are reported, and the electrochemical properties of the complexes are investigated. The copper(II) complexes are cell-permeable in A431 mammalian cells and can be radiolabeled with copper-64 at room temperature.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Ji-Hun Park, Xuran Zhang, Hyunsoo Ha, Jung Kim, Joon Choi, Kyung-Han Lee, Youngjoo Byun, Yearn Choe
Summary: This study aimed to develop a radioligand for positron emission tomography (PET) imaging of Hepsin, a potential biomarker for prostate cancer. Through the synthesis and evaluation of various ligands, a promising PET radioligand with high binding affinity and selectivity for Hepsin was selected. The radioligand exhibited high binding to prostate cancer cells and showed promising imaging results in a prostate tumor mouse model.
Article
Multidisciplinary Sciences
Agata Kubik, Anna Budzynska, Krzysztof Kacperski, Maciej Maciak, Michal Kuc, Piotr Piasecki, Maciej Wilinski, Marcin Konior, Miroslaw Dziuk, Edward Iller
Summary: The feasibility of SPECT and PET Y-90 imaging was assessed by visualizing hot and cold foci in phantoms with varying isotope concentrations. PET imaging provided better results than Bremsstrahlung based SPECT imaging, indicating its potential as the method of choice in Y-90 post radioembolization imaging.
Article
Multidisciplinary Sciences
Azmal Sarker, Minseok Suh, Yoori Choi, Ji Yong Park, Yun-Sang Lee, Dong Soo Lee
Summary: Age-related cognitive decline is associated with dysfunctional lymphatic drainage of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. In this study, [Cu-64]Cu-albumin positron emission tomography (PET) was used to evaluate CSF lymphatic drainage in mice and found that it decreased with age. The PET scan revealed that the CSF clearance half-time was significantly longer in aged mice compared to adult mice, and the activity of paravertebral lymph nodes was also lower in aged mice.
SCIENTIFIC REPORTS
(2023)
Article
Nanoscience & Nanotechnology
Sandra Diez-Villares, Juan Pellico, Noemi Gomez-Lado, Santiago Grijalvo, Sandra Alijas, Ramon Eritja, Fernando Herranz, Pablo Aguiar, Maria de la Fuente
Summary: The study explores the potential of SNs as a novel probe for nuclear imaging. The researchers developed a simple and mild method for radiolabeling SNs with Ga-68 and Ga-67 isotopes, demonstrating efficient tracking in vivo with PET and SPECT. Additionally, they found that the biodistribution of Ga-67/68-SNs can be modulated by modifying surface properties, making them adaptable for various biomedical applications.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2021)
Article
Biochemical Research Methods
Tengzhi Liu, Kathrine Roe Redalen, Morten Karlsen
Summary: Cyclotron-produced copper-64 radioisotope tracers can be used for both PET imaging and theranostic studies. The versatile chemical properties of this isotope are important for imaging tumor hypoxia. Various production and synthesis methods exist but may need further standardization and suitability for hospital settings.
JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
(2022)
Article
Biotechnology & Applied Microbiology
Jiaying Zhang, Zefang Lin, Xiaojun Zhang, Rong Lin, Mengchao Cui, Weibing Miao, Shaobo Yao
Summary: The injection of Ga-68-DOTA-DiPSMA is safe and associated with low absorbed and effective doses. Ga-68-DOTA-DiPSMA demonstrates favorable kinetics and imaging characteristics, showing potential as an alternative for gallium-68-labeled PSMA clinical PET.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Nanoscience & Nanotechnology
Xiaomin Yang, Vu Long Tran, Hynd Remita, Farah Savina, Caroline Denis, Dimitri Kereselidze, Benoit Jego, Sandrine Lacombe, Erika Porcel, Charles Truillet
Summary: Personalized medicine approach in radiotherapy requires precise delivery of dose to the tumor. High-Z metal-based nanoparticles as radio-enhancers, featured with PET imaging, show potential for clinical use.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2022)
Article
Biochemical Research Methods
Azalea A. Khan, Francis Man, Farid N. Faruqu, Jana Kim, Fahad Al-Salemee, Amaia Carrascal-Minino, Alessia Volpe, Revadee Liam-Or, Paul Simpson, Gilbert O. Fruhwirth, Khuloud T. Al-Jamal, Rafael T. M. de Rosales
Summary: This study explored the use of [Zr-89]Zr(oxinate)(4) for labeling sEVs and demonstrated the possibility of tracking labeled sEVs in vivo using PET imaging. Differential biodistribution of intentionally heat-damaged sEVs compared to intact sEVs was also observed. Therefore, this method can be reliably used to explore the potential of sEVs as drug delivery systems.
BIOCONJUGATE CHEMISTRY
(2022)
Review
Oncology
Ryan C. Perez, DaeHee Kim, Aaron W. P. Maxwell, Juan C. Camacho
Summary: The association between hypoxia, cancer aggressiveness, and decreased therapeutic response is well-established. This review aims to summarize the molecular pathways associated with tumor hypoxia and the use of PET and MRI techniques for imaging hypoxia in cancer. It also discusses future directions and challenges in this field.
Article
Oncology
Siroos Mirzaei, Rainer Lipp, Shahin Zandieh, Asha Leisser
Summary: The diagnostic performance of [Cu-64]-DOTAGA-PSMA PET-CT imaging was compared to [F-18]-PSMA PET-CT in prostate cancer patients. Both radiotracers showed comparable detection rates, with slight differences in liver uptake.
Article
Radiology, Nuclear Medicine & Medical Imaging
Julia C. Carmona-Bozo, Roido Manavaki, Ramona Woitek, Turid Torheim, Gabrielle C. Baxter, Corradina Caraco, Elena Provenzano, Martin J. Graves, Tim D. Fryer, Andrew J. Patterson, Fiona J. Gilbert
Summary: Through combined (18)F-FMISO-PET/MRI, we found a relationship between hypoxia and vascular function in breast cancer, highlighting the heterogeneity within tumour regions. Hypoxia was positively correlated with lesion size, but negatively correlated with DCE-MRI parameters.
EUROPEAN RADIOLOGY
(2021)
Article
Chemistry, Medicinal
Amaury Guillou, Eda Nisli, Simon Klingler, Anthony Linden, Jason P. Holland
Summary: Fluorescent protein conjugates are important tools in scientific research, and the synthesis of photoactivatable fluorophores provides a potential approach for protein labeling and imaging.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Simon Klingler, Jason P. Holland
Summary: This study introduces a fully automated synthesis box for the production of Zr-89-radiolabeled antibodies. The automated method eliminates the need for manual synthesis and improves the yield and purity of the radiolabeled antibodies. This will benefit the Nuclear Medicine and research institutions in accessing state-of-the-art Zr-89-radiolabeled antibodies.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Faustine d'Orchymont, Jason P. Holland
Summary: This article describes a rotaxane-based approach to synthesizing radiolabeled proteins and peptides for molecular imaging of cancer biomarkers in vivo. The technology provides a platform to explore how mechanical bonding can improve drug delivery, enhance tumor specificity, control radiotracer pharmacokinetics, and reduce dosimetry.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Medicine, Research & Experimental
Rachael Fay, Imre Toro, Anna-Lena Schinke, Branko Simic, Jonas Schaefer, Birgit Dreier, Andreas Plueckthun, Jason P. Holland
Summary: Designed ankyrin repeat proteins (DARPins) modified with enzymatic methods and Zr-89-radiolabeled can serve as a new class of protein-based radiotracers for PET, exhibiting high specificity and affinity in HER2/neu-positive tumors.
MOLECULAR PHARMACEUTICS
(2022)
Article
Multidisciplinary Sciences
Srividhya Swaminathan, Katie E. Lineburg, Archana Panikkar, Jyothy Raju, Lawton D. Murdolo, Christopher Szeto, Pauline Crooks, Laetitia Le Texier, Sweera Rehan, Michael J. Dewar-Oldis, Peter J. Barnard, George R. Ambalathingal, Michelle A. Neller, Kirsty R. Short, Stephanie Gras, Rajiv Khanna, Corey Smith
Summary: The T cell response to SARS-CoV-2 can be affected by mutations in emerging variants, reducing the effectiveness of T cell immunity. While antibody-mediated immunity may be reduced against the Omicron variant, T cell recognition is less affected. However, the complexity of human leukocyte antigen genetics suggests that T cell immunity may not be universally maintained.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Faustine d'Orchymont, Jason P. Holland
Summary: We synthesized and characterized bimodal mechanically interlocked rotaxane-based imaging agents using the cucurbit[6]uril CB[6]-mediated alkyne-azide 'click' reaction. Two synthetic routes involving four- or six-component reactions were developed to access asymmetric rotaxanes. A peptide-based rotaxane targeted toward the clinical prostate cancer biomarker, prostate-specific membrane antigen (PSMA), was synthesized with Ga-68-radiometal ion complex for positron emission tomography and fluorescein as an optically active imaging agent. The results showed the feasibility of using an asymmetric rotaxane platform to produce dual-modality imaging agents specifically targeting prostate cancer cells.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Ina Hierlmeier, Amaury Guillou, Daniel F. Earley, Anthony Linden, Jason P. Holland, Mark D. Bartholomae
Summary: In this study, we synthesized and investigated the coordination chemistry of novel copper(II) and zinc(II) complexes using two heterocyclic triazacyclononane(tacn)-based chelators (HNODThia and NODThia-AcNHEt). The modified chelator HNODThia was used to develop a PSMA-based bioconjugate (NODThia-PSMA) and a photoactivatable azamacrocyclic analogue (NODThia-PEG ( 3 ) -ArN ( 3 )) for copper-64 radiopharmaceuticals. The metal-binding chelates showed rapid radiolabeling, stability in human plasma, and successful photoconjugation to albumin and antibodies. These findings have significant implications for the development of stable Cu-64-based radiopharmaceuticals and the future application of Cu-67 in targeted radioimmunotherapy.
INORGANIC CHEMISTRY
(2023)
Article
Agriculture, Dairy & Animal Science
Lavinia E. Chiti, Brian Park, Faustine d'Orchymont, Jason P. Holland, Mirja C. Nolff
Summary: The use of near-infrared fluorophores has promising applications in surgical oncology. The performance of dedicated camera systems is affected by the lighting condition of the operating theatre. LED and halogen lights have a detrimental effect on the diagnostic performances of the camera systems. Surgeons should evaluate the spectral contribution of the lights when implementing fluorescence-guided surgery (FGS) into the clinical routine.
Article
Biochemistry & Molecular Biology
Melanie Gut, Birgit Dreier, Sven Furler, Jens Sobek, Andreas Pluckthun, Jason P. Holland
Summary: Late-stage prostate cancer often becomes resistant to standard chemotherapy and transforms into a hormone-resistant, drug-resistant, and incurable disease. Developing non-invasive tools to detect biochemical changes that indicate drug efficacy and identify drug resistance could have significant implications in managing individual patients' treatment plans. In this study, new Designed Ankyrin Repeat Proteins (DARPins) with high affinity for prostate-specific antigen (PSA) were selected using ribosome display and in vitro screening tools. These PSAbinding DARPins showed nanomolar affinity for PSA and could be radiolabeled for potential use in imaging-based monitoring of androgen receptor (AR)-targeted therapies.
RSC CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Faustine D'Orchymont, Jason P. Holland
Summary: In this study, a unique rotaxane-antibody conjugate was developed for PET imaging and quantification of specific tumor receptors. The experimental results showed that the rotaxane-radiotracer has improved pharmacokinetic properties and reduced radiation exposure to critical organs.
Article
Chemistry, Inorganic & Nuclear
Joel C. Mather, Jessica A. Wyllie, Alex Hamilton, Tatiana P. Soares da Costa, Peter J. Barnard
Summary: A series of gold(I) and silver(I) complexes were synthesized and their antibacterial activities were tested. The gold(I) complexes showed good activity against Gram-positive bacteria, with the complexes of the 1,2,4-triazolylidene ligands being more active. The silver(I) complexes exhibited good antibacterial activity against Acinetobacter baumannii. High levels of antibacterial activity were observed against multi-drug resistant bacterial strains for both the gold(I) and silver(I) complexes. Resistance to these metal-containing complexes was less likely to develop compared to the widely used broad-spectrum antibiotic. Furthermore, the stability of these complexes was investigated, revealing possible decomposition reactions for silver complexes in aqueous solution.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Inorganic & Nuclear
Amaury Guillou, Ali Ouadi, Jason P. Holland
Summary: In this study, the synthesis of bifunctional heptadentate metal ion binding chelates derived from DFO linked to a tripeptide unit was reported. The chelates were functionalised with a photoactivatable aryl azide unit for light-triggered labelling of proteins. The results showed that the chelates had good radiolabelling efficiency with zirconium-89 and exhibited high stability in the presence of different competitors. PET imaging and biodistribution studies further confirmed the pharmacokinetic profile and tumor binding of the chelates in nude mice bearing human gastric cancer xenografts.
INORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Daniel F. Earley, Amaury Guillou, Simon Klingler, Rachael Fay, Melanie Gut, Faustine d'Orchymont, Shamisa Behmaneshfar, Linus Reichert, Jason P. Holland
Summary: This study reports on the light-triggered synthesis of human serum albumin using a series of photoactivatable DFO derivatives. The findings demonstrate that photochemistry is a viable option for making diverse, functionalized protein conjugates.
Article
Chemistry, Inorganic & Nuclear
Nuchareenat Wiratpruk, Guneet K. Bindra, Alex Hamilton, Mark D. Hulett, Peter J. Barnard
Summary: A family of rhenium(i) tricarbonyl complexes with pyridyl-imidazolylidene or bis-imidazolylidene ligands in combination with a series of N-acetyl amino acids ligands and an acetate have been synthesized and characterized. These complexes show potential as anticancer agents, with the ability to exchange the bound carboxylate ligand with water to form cytotoxic cationic complexes. Cytotoxicity studies reveal that the complexes with the bis-imidazolylidene ligand exhibit higher toxicity compared to those with the pyridyl-imidazolylidene ligand.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Inorganic & Nuclear
Daniel F. Earley, Jose Esteban Flores, Amaury Guillou, Jason P. Holland
Summary: In recent years, copper-64 and copper-67 have been considered as a useful theranostic pair in nuclear medicine. This study successfully demonstrates the viability of photochemically induced conjugation methods for the development of copper-based radiotracers for potential applications in diagnostic PET imaging and targeted radionuclide therapy.
DALTON TRANSACTIONS
(2022)