SP-103 - Scandium-47 and lutetium-177 radiolabelling and stability studies of 1st and 2nd generation DOTA-triphenylphosphonium ligands – potential radionuclide theranostics for treatment of glioblastoma multi-forme

Scandium-47 has emerged as a promising radioisotope for targeted radionuclide tumor therapy. This is due, to a significant extent, from the combination of low energy / short range β- emission, the availability of a “perfect theranostic pair” with Sc-44 for companion PET imaging, the potential to form highly stable radiometal complexes, and the availability of suitable γ emissions for companion SPECT imaging. Sc-47 also has a shorter half-life (3.35 d) than the chemically similar Lu-177 (6.7 d) which is significant given recent in vitro research that suggests longer lived isotopes require more initial radioactivity to have the same effect upon cell viability [3]. The shorter half-life of Sc-47 also suggests it may be more suitable for smaller biological vectors (with shorter biological half-lives) such as small molecules and low MW peptides. One area of clinical treatment where Sc-47 can have impact and where improvements in patient outcomes and survival rates remain stubbornly low is glioblastoma multiforme (GBM). GBM is the most common and aggressive form of malignant brain tumor and represents around 60% of all adult brain tumors with a global incidence of <10 per 100,000 persons. The prognosis for GBM patients is poor with a -ear survival rate of 37%, 5 year rate of 5% and a median survival time of 10 months. The current standard of treatment is resection of the tumor followed by radiation therapy and chemotherapy. Given this poor prognosis there is a clear and unmet need for improved classes of treatment. Although significant progress has been made towards bringing GBM targeted radionuclide therapies to the clinic, the efforts to date have not included utilizing Sc-44/ Sc-47. Given this we are developing and evaluating Sc-44/Sc-47 and Lu-177/Ga-68 radiolabelled triphenylphosphonium (TPP) functionalised DOTA ligands (1st and 2nd generation) as potential theranostics for GBM. Described herein is our work on comparing the radiolabelling efficiency (Sc-47 vs. Lu-177) and stability studies (PBS pH 7.4, rat plasma) for our 1st and 2nd generation DOTA-TPP ligands. The presence of an additional carbonyl group in the 2nd generation DOTATPP ligand was anticipated to increase the number of donor atoms around the radiometal and affect radiolabelling reaction conditions and, more importantly, increase radiometal complex stability. Copyright © 2021 Elsevier Inc.

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Keywords

Radioisotopes, Lutetium 177, Scandium 47, Stability, Ligands, Theranostics, Gliomas, Therapy

Citation

Wyatt, N., Hogan, L., Pellegrini, P., Roberts, M., Hall, A., Smith, N., Hemzal, E., Hill, L., Howell, N., Middleton, R., Safavi-Naeini, M., Rendina, L. & Fraser, B. (2021). SP-103 - Scandium-47 and lutetium-177 radiolabelling and stability studies of 1st and 2nd generation DOTA-triphenylphosphonium ligands – potential radionuclide theranostics for treatment of glioblastoma multi-forme. Paper presented at the Society of Radiopharmaceutical Sciences eSRS Virtual Meeting 2021, 17 to 19 May 2021. In Nuclear Medicine and Biology, 96–97 (Supp. 1), S93-S94. doi:10.1016/S0969-8051(21)00420-0

URI

https://doi.org/10.1016/S0969-8051(21)00420-0
https://apo.ansto.gov.au/dspace/handle/10238/10977

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