Abstract
In recent years, the use of metallic isotopes for nuclear imaging techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) has become an area of much interest. In particular, PET is a molecular imaging modality that relies on the detection of two antiparallel, co-linear gamma rays (511 keV) emitted when a positron undergoes annihilation with an electron. PET isotopes of interest in medical practice are numerous and their use depends on their half-lives and introduction in the compounds of interest. These include: nitrogen-13 (t1/2 = 10 min), carbon-11 (t1/2 = 20 min), fluorine-18 (t1/2 = 110 min) and metallic isotopes such as gallium-68 (t1/2 = 68 min), titanium-45 (t1/2 = 3.08 h), copper-64 (t1/2 = 12.7 h), manganese-52 (t1/2 = 5.59 d) or zirconium-89 (t1/2 = 3.3 d). 89Zr has emerged as a promising isotope for radiotracer design and in vivo delivery, on basis of its ideal half-life matching the biological half-life of antibodies, antibody fragments and nanomedicines leading to high-resolution PET images for the pre-clinical and clinical investigations of a number of conditions including the prospective use in prostate cancers in the search of new diagnostic biomarkers. The availability of a plethora of chelators satisfying the coordination number of 8 such as siderophore-like chelators and recently nanoparticles conferring high kinetic and thermodynamic stabilities provides various designs and versatility in chemistry and radiochemistry. The aqueous chemistry of 89Zr is certainly of high importance for antibody-based imaging due to the match between the physical half- life of the nuclide and the biological half-life of the targeting vector, but mostly if there are no small molecules with more rapid pharmacokinetics available. This mini-review highlights some of the recently accounted advantages and disadvantages of current biomolecule-tagging techniques and proposes subtle radiotracer design changes that may be introduced in order to obtain a highly efficient targeted imaging with zirconium-labelled chemical entities and nanoconstructs. These may be of relevance to preclinical and clinical research towards the diagnosis of cancer in general, whilst highlighting some of the prostate cancer targeting approaches from the recent 89Zr-focused radiochemistry literature.
| Original language | English |
|---|---|
| Article number | 119041 |
| Journal | Inorganica Chimica Acta |
| Volume | 496 |
| Early online date | 1 Aug 2019 |
| DOIs | |
| Publication status | Published - 1 Oct 2019 |
Funding
We are grateful to Professor Jonathan Dilworth for helpful discussions and to Mr Ruediger Exner for comments on the manuscript. SIP thanks the EPSRC (EP/G03768X/1) and ERC ‘O2Sense’ Consolidator grant (617107) for funding. Prof Sofia Pascu is a European Research Council Consolidator Fellow (2014-2019) and former holder of a Royal Society URF (2005-2015). She is an expert in transition metal complexes for cellular confocal fluorescence imaging, in the design of metal-based radiopharmaceuticals for PET/SPECT imaging and detection of reactive oxygen species implicated in non-communicable diseases including cancer (h-30, 100 publications). She is a researcher in residence at RAL, with Prof Stan Botchway, and Academic Visitor at the Oxford Siemens Molecular Imaging Laboratory (with Profs S. Faulkner and J. Dilworth, 2007-Date) and has trained extensively in the use of metallic radioisotopes such as 68 Ga, 64 Cu and 111 In for multimodality imaging, at the Wolfson Brain Imaging Centre, Cambridge (with Prof F. Aigbirhio) and at Memorial Sloan Kettering Cancer Centre (with Prof J. Lewis). Prior to embarking on her independent academic career she completed a DPhil in transition metals chemistry with Professor Malcolm L.H. Green FRS (1998-2002) and held a PDRA position within the same research group (2002-2003) followed by a PDRA position at the University of Cambridge with Professor Jeremy K.M. Sanders FRS (2003-2005). Fernando Cortezon Tamarit is a Research Fellow at the University of Bath developing research in molecular probes for the imaging of hypoxia under the O2SENSE ERC project on the team of Prof Pascu. During his PhD completed in 2016 he carried out research in imaging probes for prostate cancer as part of the Marie Curie ITN PROSENSE. The targeted imaging probes synthesised during his recent experience include metal complexes with a variety of ligands, organic fluorophores for sensing and carbon nanomaterials. Agata Baryzewska is a former BSc and Master’s student of the Department of Chemistry at the University of Bath, whom graduated in Summer 2018 and recently embarked onto the start of a PhD Degree at the Max Planck Institute of Colloids and Interfaces, Potsdam, Germany. Marina Lledos graduated in Chemistry from the Universitat de Barcelona in 2010. As an undergraduate student, she completed a short project in the Group of Magnetism and Functional Molecules, with Dr Albert Figuerola, working in the synthesis and characterisation of nanoparticles with magnetic and plasmonic properties. She was an Erasmus student at the University of Aberdeen, where she did her final year research project in the Solid State Chemistry research group of Dr Abbie C. McLaughli. on the synthesis and characterisation of Ruddlesden popper phases. In summer 2010, she was awarded a Summer Fellowship to carry out a short research project at the Institute of Chemical Research of Catalonia (ICIQ) within the Photomagnetic Materials and Bioinorganic Models for Energy Applications group of Prof Jose Ramon Galan-Mascaros. She completed a PhD at the University of Bath (2014-2018) in the group of Prof Sofia Pascu, and with Dr Ian Eggleston as a second supervisor. During her PhD, Marina worked in the synthesis of new multimodal probes for medical (PET/ SPECT and MRI) and optical imaging applications. In 2018 she also performed research as a casual research assistant position in Prof Sofia Pascu's ERC O2Sense team. Marina joined Dr. Mischa Zelzer's group as a research fellow in surface-directed supramolecular self-assembly in September 2018.
Keywords
- Chemical biology
- Metals in medicine and nanomedicine
- Siderophores for PET imaging and radiochemistry
- Zirconium-89 aqueous chemistry
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Inorganic Chemistry
- Materials Chemistry