Radiopharmaceutical Science Community of Practice: Novel theranostics targeting the oncoprotein R0R1

Radiopharmaceutical Science Community of Practice: An initiative to promote radiopharmaceutical science in Australia

The Peter MacCallum Cancer Centre at the University of Melbourne will host Dr Joseph Van de Garde for the first lecture of 2026 on “Novel Theranostics Targeting the Oncoprotein R0R1”.

Join on Microsoft Teams with the event location link.

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Abstract

Peptide-based theranostics are highly suited for cancer imaging and therapy due to their favourable pharmacokinetics,
including rapid tissue penetration, high specificity, and fast clearance from non-target tissues. ROR1, a transmembrane
oncoprotein expressed in several aggressive cancers but largely absent from normal adult tissues, presents a promising
molecular target for selective theranostic development. Here, we report the discovery and characterisation of a new class
of radiolabelled macrocyclic peptides targeting ROR1, identified using the RaPID (Random nonstandard Peptide Integrated
Discovery) platform. Following six iterative selection cycles against recombinant ROR1, several peptide candidates were
enriched and chemically synthesised. The top three lead compounds exhibited subnanomolar affinity (<1 nM) by surface
plasmon resonance, retained high binding affinity following DOTA conjugation and radiolabelling with Gallium-68 and
Lutetium-177, and demonstrated excellent radiochemical purity (>97%). Cell-based saturation binding assays confirmed
specific and high-affinity interactions with ROR1-expressing cancer cells. In vivo imaging and biodistribution studies in
xenograft models further validated the ability of these peptides to selectively target ROR1-expressing tumours. These
findings establish the first macrocyclic peptide ligands targeting ROR1 with high affinity and favourable pharmacokinetic
properties, supporting their potential as next-generation radiopharmaceuticals for the detection and treatment of ROR1-
positive malignancies.

Biography, Dr Joseph Van de Garde

Dr Joseph Van de Garde completed his Bachelor of Biomedical Science (Hons) at the Australian Catholic University in
2020, after beginning his studies as a Biochemistry student in Kansas City (2014–17). He went on to earn his PhD in
Radiopharmaceutical Science at the University of Melbourne, with his research based at the Peter MacCallum Cancer
Centre, where he developed novel theranostics targeting the oncoprotein ROR1. Joseph is now working as a
Radiopharmaceutical Scientist at the Peter MacCallum’s Cancer Imaging Department, applying his expertise in peptide,
radio and computational chemistry. Alongside his research and professional work, he has taught chemistry and biology at
both the University of Melbourne and ACU and continues to enjoy mentoring students in the sciences.