Targeted Radionuclide Therapy (TRT) is one of the most rapidly advancing research areas in oncology, enabling the precision delivery of cytotoxic ionising radiation to tumour tissue through the deliberate design of radiopharmaceutical agents incorporating a relevant radioisotope. The rhenium-188/technitium-99m pair constitutes a compelling opportunity for the development of a theranostic matched pair for TRT and Single Photon Emission Computed Tomography (SPECT) diagnostic imaging respectively. This relationship arises not only from the favourable nuclear decay properties of the radiometal isotopes, but also their remarkably similar coordination chemistry as Group 7, 4d and 5d congeners. The development of a ligand system capable of stabilising these radiometals in intermediate oxidation states within a physiological environment is paramount to the development of clinically applicable radiopharmaceutical agents. The SHYNIC ligand system represents a versatile bifunctional chelation strategy, enabling the production of structurally discrete {M=O}3+ square-based pyramidal complexes of technetium and rhenium with sites available for biochemical functionalisation.
This work describes the preliminary development of two classes of SHYNIC based 188Re and 99mTc radiopharmaceutical agents. The first of which incorporated opposing pendant bisphosphonate moieties, capable of selective localisation to sites of bone tumour, with 99mTc and 188Re analogues proposed for use as a diagnostic imaging tool and palliative treatment for pain associated for bone metastasis. The second incorporates an antagonistic peptidyl targeting vector with high affinity and selectivity for Gastrin Releasing Peptide Receptor (GRPR), for the targeted imaging and therapy of GRPR-positive neoplasms, which constitute a large portion of all instances of prostate, breast and lung cancers.