Development of novel acyclic chelators for gallium-68 and scandium-44 used in PET
Lead Research Organisation:
King's College London
Department Name: Imaging & Biomedical Engineering
Abstract
This proposal sets out to make the next generation of radiotracers using gallium-68 and scandium-44 for use positron emission tomography (PET), which can be rapidly radiolabelled under physiological conditions for easy translation into the clinic and make the process of production of imaging agent significantly quicker and easier for the radipharmist to undertake. this project is designed to take the novel ligands and apply them to the clinical equipment used currently for production of imaging agents and make this process faster and more efficient. This project will develop a series of bifunctional ligands for this to allow for imaging of prostate cancer using gallium-68 and scandium-44, and validate the radiolabeling potential in the latest microfluidic technology for rapid translation to radiopharmacy use for GMP production.
These agents will be capable of taking a radiolabel directly to a cancerous site and allowing the tumour to be easily visualized by positron emission tomography (PET) imaging. Using this information, a related carrier molecule will then deliver a radioactive payload to the cancerous tumour with minimal damage to the surrounding tissue. The guiding system will comprise peptide groups which have an affinity for motifs (receptors) that are overexpressed at the cancerous tumour.
The named research groups have been selected given that they contribute complementary expertise to that available in the PIs group at KCL and Hull, with a mix of inorganic chemistry, biology, PET imaging and microfluidic technology. Regular meetings/workshops between the named groups, clinicians and radiopharmacists will ensure a validation pathway for the new agents.
Use of local science forums and blogs will enable the team to engage with the public and patients.
This project will progress with commercialization in mind and the need to minimise both the complexity (number of steps) of the design of these chelators and also the need to optimize wider utilization at the 'bed-side', i.e. mild conditions and limited radioactive steps.
These agents will be capable of taking a radiolabel directly to a cancerous site and allowing the tumour to be easily visualized by positron emission tomography (PET) imaging. Using this information, a related carrier molecule will then deliver a radioactive payload to the cancerous tumour with minimal damage to the surrounding tissue. The guiding system will comprise peptide groups which have an affinity for motifs (receptors) that are overexpressed at the cancerous tumour.
The named research groups have been selected given that they contribute complementary expertise to that available in the PIs group at KCL and Hull, with a mix of inorganic chemistry, biology, PET imaging and microfluidic technology. Regular meetings/workshops between the named groups, clinicians and radiopharmacists will ensure a validation pathway for the new agents.
Use of local science forums and blogs will enable the team to engage with the public and patients.
This project will progress with commercialization in mind and the need to minimise both the complexity (number of steps) of the design of these chelators and also the need to optimize wider utilization at the 'bed-side', i.e. mild conditions and limited radioactive steps.
People |
ORCID iD |
| Graeme Stasiuk (Principal Investigator) |
Publications
Alshamrani AFA
(2021)
Scandium calix[n]arenes (n = 4, 6, 8): structural, cytotoxicity and ring opening polymerization studies.
in Dalton transactions (Cambridge, England : 2003)
Anbu S
(2023)
ATP-responsive Mn( ii )-based T 1 contrast agent for MRI
in Chemical Communications
Brito B
(2023)
Redox double-switch cancer theranostics through Pt(IV) functionalised manganese dioxide nanostructures.
in Nanoscale
Gape P
(2024)
Towards Effective Targeted Alpha Therapy for Neuroendocrine Tumours: A Review
in Pharmaceuticals
Price T
(2023)
Inorganic Chemistry of the Tripodal Picolinate Ligand Tpaa with Gallium(III) and Radiolabeling with Gallium-68
in Inorganic Chemistry
Price TW
(2022)
Bn2DT3A, a Chelator for 68Ga Positron Emission Tomography: Hydroxide Coordination Increases Biological Stability of [68Ga][Ga(Bn2DT3A)(OH)].
in Inorganic chemistry
Rosecker Veronika
(2023)
Scale-up and optimisation of
199Au production from
natPt
0 and successful
199Au-labelling of bis-pyridine
in NUCLEAR MEDICINE AND BIOLOGY
Scialla S
(2022)
Insights into the Effect of Magnetic Confinement on the Performance of Magnetic Nanocomposites in Magnetic Hyperthermia and Magnetic Resonance Imaging.
in ACS applied nano materials
| Description | we have developed a molecule that binds the radiocative metal gallium-68, under mild natural conditions, this molecule has undergo multiple rounds of testing and further modified to target it to prostate cancer. |
| Exploitation Route | This is too early to say as the award is still active, but it would be of use in translation to imaging centers for the diagnosis of prostate cancer in the future. |
| Sectors | Chemicals Healthcare |
| Description | MRIP program by BEIS, on long term strategy for radionuclides for health |
| Geographic Reach | National |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Description | Development of PET/PDT theranostics for High Grade Glioma |
| Amount | £161,901 (GBP) |
| Organisation | Cancer Research UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2023 |
| End | 09/2027 |
| Description | Development of production of Scandium-44 and Manganese-52 for preclinical and clinical PET imaging - EPSRC IAA-KCL |
| Amount | £61,089 (GBP) |
| Organisation | King's College London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 05/2021 |
| End | 05/2022 |
| Description | Inorganic nanoparticles for radiolabelling with 223Ra / 212Pb, for multimodal imaging and therapy in cancer. EPSRC -SMART IMAGING CDT/NNL |
| Amount | £115,000 (GBP) |
| Organisation | King's College London |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 08/2022 |
| End | 08/2026 |
| Description | State-of-the-Art Equipment for Preclinical Molecular Imaging and Targeted Radiotherapy |
| Amount | £168,000 (GBP) |
| Funding ID | MR/X011992/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2022 |
| End | 03/2023 |
| Description | State-of-the-Art Equipment for Preclinical Targeted Radiotherapy |
| Amount | £416,920 (GBP) |
| Funding ID | MC_PC_MR/Y000242/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 06/2023 |
| End | 03/2024 |
| Title | CCDC 1864389: Experimental Crystal Structure Determination |
| Description | Related Article: Thomas W. Price, Isaline Renard, Timothy J. Prior, Vojte?ch Kubi´c?ek, David M. Benoit, Stephen J. Archibald, Anne-Marie Seymour, Petr Hermann, Graeme J. Stasiuk|2022|Inorg.Chem.|61|17059|doi:10.1021/acs.inorgchem.2c01992 |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc20l1l8&sid=DataCite |
| Title | CCDC 1878045: Experimental Crystal Structure Determination |
| Description | Related Article: Thomas W. Price, Laure`ne Wagner, Veronika Rosecker, Jana Havli´c?kova´, Timothy J. Prior, Vojte?ch Kubi´c?ek, Petr Hermann, Graeme J. Stasiuk|2023|Inorg.Chem.|62|20769|doi:10.1021/acs.inorgchem.3c02459 |
| Type Of Material | Database/Collection of data |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc21183h&sid=DataCite |
| Title | CCDC 2125953: Experimental Crystal Structure Determination |
| Description | Related Article: Thomas W. Price, Isaline Renard, Timothy J. Prior, Vojte?ch Kubi´c?ek, David M. Benoit, Stephen J. Archibald, Anne-Marie Seymour, Petr Hermann, Graeme J. Stasiuk|2022|Inorg.Chem.|61|17059|doi:10.1021/acs.inorgchem.2c01992 |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| URL | http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc29c742&sid=DataCite |
| Description | Inorganic nanoparticles for radiolabelling with 223Ra / 212Pb, for multimodal imaging and therapy in cancer. |
| Organisation | National Nuclear Laboratory |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | We are developing radiotherapy nanoparticles (Quantum dots) |
| Collaborator Contribution | NNL have sponsored a PhD student in my research group under the topic above, this started in September 2022. |
| Impact | none so far. |
| Start Year | 2022 |