Project 1 – Theranostic Radioscandium: From Production to Radiolabelling
Project supervision:
Monash: Prof Andrea Robinson and Dr Adam Kennedy; HZDR: Dr Martin Walther and Dr Constantin Mamat
Project description:
Radioscandium isotopes offer a promising theranostic alternative among a limited number of true theranostic radionuclide sets. This project will explore the production of positron emitters ⁴³Sc and ⁴⁴Sc from natural or enriched calcium targets. The β⁻ emitter ⁴⁷Sc will be produced using natural vanadium targets. Purification processes will build on established literature methods and HZDR’s experience in radiochemical target processing. These processes will be further optimized and adapted for fully automatization e.g. with an iPhase module. Quality control of the produced radioscandium will involve gamma spectroscopy, ICP-OES analysis, and test radiolabelling with appropriate chelators to ensure radiochemical purity and suitability for future applications.
Ideal skills needed for project:
Strong synthetic, analytical and organometallic chemistry skills. Chelate design and labelling.
Project 2 – Theranostic Radiomercury: Radiolabelling and Application in Mercury Analytics
Project supervision:
Monash: Prof Andrea Robinson and Dr Adam Kennedy; HZDR: Dr Santiago Andres Brühlmann and Dr Martin Kreller
Project description:
Radiomercury isotopes, especially the pair 197(m)Hg, offer a promising theranostic alternative among limited number of Meitner-Auger emitting radionuclides. This project focuses on peptidomimetic and precursor synthesis and radiomercury labelling methods exploiting click labelling approaches. To make the 197(m)Hg accessible for different target molecules, a click-labelling toolbox consisting of a labelling building block containing 197(m)Hg is in the focus. Additionally, the precursor compounds will be investigated for their potential application as new analytical methods for stable Hg detection. Radiomercury production will build on established methods and HZDR’s experience in radiochemical target processing.
Ideal skills needed for project:
Strong synthetic chemistry and analytical skills. This project will expose students to small molecule synthesis, peptidomimetic design and synthesis, and radiolabelling.
Project 3 – Metallopeptides for Bioremediation in Multi-Metal Environments
Project supervision:
Monash: Prof Andrea Robinson and Dr Adam Kennedy; HZDR: Dr Manja Kubeil, Dr Susanne Sachs and Dr. Björn
Project description:
Australia and Germany have significant legacies of anthropogenically mobilised heavy metals (including Hg, U, Pb and Cd) throughout the environment. Toxic metal contamination of environments, specifically soils and waterways, present a threat to local flora and fauna. It is well known that phytoremediation can be used to immobilise contaminants in the root zone of the plant. This project will examine stabilisation mechanisms exploited by heavy metal tolerant plant species, rational design and synthesis of selective M+ binding chelators, and structural evaluation (i.e. stoichiometry, thermodynamic stability and kinetic inertness) of complexes using techniques such as nuclear magnetic resonance, time-resolved laser fluorescence spectroscopy and isothermal titration calorimetry.
Ideal skills needed for project:
Strong synthetic and organometallic chemistry skills. Chelate design and labelling. Environmental pot trials and radiotracer analysis.
Project 4 – Fundamental Studies in Ligand Architecture and Coordination Chemistry
Monash: Prof Christoph Hagemeyer and Assoc Prof Karen Alt; Bio21
Project description:
In collaboration with Bio21, this project focuses on the design and synthesis of novel metal chelators for radioisotopes. The research will explore fundamental aspects of ligand design, coordination chemistry, and metal–ligand interactions across a range of metal ions. Emphasis will be placed on understanding structure–property relationships using experimental techniques. The project is grounded in fundamental chemistry, with no medical focus, and offers opportunities for interdisciplinary collaboration and advanced method development.
Ideal skills needed for project:
Synthetic organic skills and analytical science.
Project 5 – New Approaches for 18F Radiolabelling
Project supervision:
Monash: Prof Andrea Robinson,Dr Maggie Aulsebrook, Prof Michelle McIntosh and Dr Adam Kennedy; HZDR: Dr Gregory Bowden and Prof Dr Andreas Maurer
Project description:
Sulfur(VI) fluoride exchange (SuFEx) chemistry represents one of the most recent click chemistry transformations. Of particular appeal is the suitability of aryl sulfonyl fluoride and aryl fluorosulfate groups as warheads for in situ covalent targeting of protein binding domains. Radiotheranostic extension of this chemistry will be explored in this project via orthogonal radiolabelling, i.e. [18F]fluoride in combination with radiolabelled (e.g. 68Ga and 64Cu) chelators such as DOTA, NOTA or NODAGA. While radiometal complexation usually easily achieved, the 18F-labeling is more challenging and needs to be developed. This project will design and synthesise arylfluorosulfate functionalised peptides with orthogonal radiolabelling motifs and investigate their covalent bond forming capability to target proteins by appropriate methods. Of particular interest will be the detection of potentially released [18F]fluoride upon successful covalent bond formation.
Ideal skills needed for project:
Strong synthetic chemistry, formulation and analytical skills. This project will expose students to small molecule synthesis, peptidomimetic design and synthesis, radiolabelling and biodistribution studies.
Project 6 – A New Approaches for 18F Radiolabelling
Project supervision:
Monash: Prof Andrea Robinson and Dr Adam Kennedy; HZDR: Dr Gregory Bowden and Prof Dr Andreas Maurer
Project description:
The inclusion of bioisosteres (chemical moieties with similar but distinct properties to common moieties like substituted phenyl rings) is increasingly recognized as a tool for subtly modulating the pharmacological properties of bioactive small molecules. The unique chemical reactivity and synthesis profiles of bioisosteres such as bicyclo[1.1.1]pentane (BCP) are currently being studied and explored by the broader pharmaceutical industry for the rapid generation of molecular diversity for compound screening. The potential of bioisosteres in radiopharmaceutical discovery and development remains under-explored. This project will focus on the preliminary screening, discovery, and optimization of new radiochemical methods for bicyclic bioisostere radiolabelling.
Ideal skills needed for project:
Strong synthetic chemistry and analytical skills. This project will expose students to small molecule synthesis, peptidomimetic design and synthesis, and radiolabelling.
Project 7 – Direct Labelling of Peptide Targets
Project supervision:
Monash: Prof Philip Chan; Liverpool Hospital: Dr Nigel Lengkeek
Project description:
Direct fluorine-18 radiolabelling of peptides via C–F bond formation remains a major synthetic challenge. Current methods rely on 18F-prosthetic groups (e.g., [18F]SFB, [18F]2-fluoropropionate) or heteroatom–18F strategies such as [18F]Al–F and [18F]Si–F, which require multistep radiosyntheses and purification prior to peptide conjugation. These processes are complex, time-consuming and often give low overall radiochemical yields.
Traditional [18F]Prosthetic Groups
[18F]AlF and [18F]SiF chemistry
In this context, the development of direct, one-pot radiolabelling with minimal post-labelling steps would significantly improve access to 18F-labelled peptides. In this project, we will address this synthetic challenge by using RGD as the model peptide due to its widespread use in radiopharmaceutical research, the low-cost availability and ease of modification of cyclic analogues. Added to this is the high tolerance of modifications outside the RGD motif and readily available suitable animal models for preclinical evaluation.
We will examine a wide variety of modifications of the valine (V) residue with non-natural amino acids such as the two possible examples given below, to allow both the radiolabelling to be optimised as well the protecting/deprotecting group strategy of the other residues to align with the F-18 fluorination chemistry. We will also develop mild methods such as deoxyfluorination or catalytic fluorination to preserve peptide stability.
Cyclic RGD; c(RGD)
Base peptide
Fluorinated Analogues
Use of the c(RGDfV) as the basis for structural modification. The phenylalanine (F) is often retained or substituted with tyrosine (Y) The valine (V) is the most common site of functionalisation.
Substitution of valine (V) for Threonine (T) and subsequent transformation into 3-fluorohomoalanine.
Substitution of valine (V) for 4-hydroxyproline (O) and subsequent transformation into 4-fluoroproline.
Ideal skills needed for project:
The candidate needs to possess strong synthetic organic chemistry skills and demonstrated experience in homogeneous catalysis. They need to possess the ability to collaborate effectively within a research team while also taking the lead and working independently when the situation calls for it.