New chemical platforms for targeted radiopharmaceu.. (Radiopharm Metal Iso)
New chemical platforms for targeted radiopharmaceuticals based on generator-produced metal isotopes
(Radiopharm Metal Iso)
Date du début: 1 mars 2013,
Date de fin: 28 févr. 2015
Targeted radiopharmaceuticals for diagnosis and therapy are important in the development of a personalised medicinal approach in oncology. The radiometal isotopes, Ga-68, Tc-99m and Re-188 are particularly useful as they are sourced from a generator and their decay properties are amenable to PET diagnosis, SPECT diagnosis and radiotherapy respectively. This project aims to develop new radiochemical platforms for these isotopes, expanding their utility in nuclear medicine. For Tc-99m and Re-188, multivalent bifunctional chelators will be synthesised, which will be conjugated to the bone cancer targeting group, bisphosphonate, or an analogue of the melanoma targeted peptide, alpha-melanocyte stimulating hormone (aMSH). The new radiolabeled tetravalent compounds will be assessed for targeting efficacy using in vitro and in vivo models. Furthermore, in vivo experiments will determine whether any enhanced tumour accumulation for aMSH-derived multivalent tracers radiotracers (relative to analogues of lower valency) is truly a multivalent effect or a result of prolonged bioavailability. In the case of Ga-68, a novel pretargeting, “reverse-multivalent” approach will be developed, with the aim of decreasing radiation present in non-target organs. This requires multiple copies of a chelating group to be attached to a targeting agent, in this case, an aMSH analogue. This unlabelled agent will bind to the target receptor in vivo prior to injection of a Ga-68 formulation. Complexation of the radiometal at the in vivo target site will be achieved through incorporation of a chelating group that demonstrates high affinity and rapid binding for Ga3+. These new radiochemical platforms for generator-produced isotopes will be developed with a view to clinical translation in the multidisciplinary environment at the Division of Imaging Sciences, King’s College London.
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