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Accelerator-Based Production of Scandium Radioisotopes for Applications in Prostate Cancer: Toward Building a Pipeline for Rapid Development of Novel Theranostics

Published

Author(s)

Jason Meier, Hannah Zhang, Richard Freifelder, Mohammed Bhuiyan, Phillip Selman, Megan Mendez, Pavithra Kankanamalage, Thomas Brossard, Antonino Pusateri, Hsiu-Ming Tsai, Lara Leoni, Sagada Penano, Kaustab Ghosh, Brittany Broder, Erica Markiewicz, Amy Renne, Walter Stadler, Ralph Weichselbaum, Jerry Nolen, Chien-Min Kao, Satish Chitneni, David Rotsch, Russell Szmulewitz, Chin-Tu Chen

Abstract

In the field of nuclear medicine, the β+ emitting 43Sc and β- emitting 47Sc are promising candidates in cancer diagnosis and targeted radionuclide therapy (TRT) due to their fa-vorable decay schema and shared pharmacokinetics as a true theranostic pair. Addition-ally, scandium is a group-3 transition metal (like 177Lu) and exhibits affinity for DOTA-based chelators, which have been studied in-depth, making the barrier to implementation lower for 43/47Sc than other proposed true theranostics. Before 43/47Sc can see widespread pre-clinical evaluation, however, an accessible production methodology must be estab-lished and each isotope's radiolabeling and animal imaging capabilities studied with a widely utilized tracer. As such, a simple means of converting an 18 MeV biomedical cyclo-tron to support solid targets and produce 43Sc via the 42Ca(d,n)43Sc reaction has been de-vised exhibiting reasonable yields. The NatTi(γ,p)47Sc reaction is also investigated along with the successful implementation of chemical separation and purification methods for 43/47Sc. The conjugation of 43/47Sc with PSMA-617 at specific activities of up to 8.94 MBq/nmol and the subsequent imaging of LNCaP-ENZaR tumor xenografts in mouse models with both 43/47Sc-PSMA-617 is also presented.
Citation
Molecules
Volume
28
Issue
16

Keywords

Theranostics, PSMA-617, Prostate Cancer, mCRPC, PET, SPECT, TRT, Scandium-43, Scandium-47, Radioisotopes

Citation

Meier, J. , Zhang, H. , Freifelder, R. , Bhuiyan, M. , Selman, P. , Mendez, M. , Kankanamalage, P. , Brossard, T. , Pusateri, A. , Tsai, H. , Leoni, L. , Penano, S. , Ghosh, K. , Broder, B. , Markiewicz, E. , Renne, A. , Stadler, W. , Weichselbaum, R. , Nolen, J. , Kao, C. , Chitneni, S. , Rotsch, D. , Szmulewitz, R. and Chen, C. (2023), Accelerator-Based Production of Scandium Radioisotopes for Applications in Prostate Cancer: Toward Building a Pipeline for Rapid Development of Novel Theranostics, Molecules, [online], https://doi.org/10.3390/molecules28166041, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=956363 (Accessed May 28, 2024)

Issues

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Created August 13, 2023, Updated October 23, 2023