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

Published

August 13, 2023

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

Pub Type

Journals

Download Paper

https://doi.org/10.3390/molecules28166041

Local Download

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 April 28, 2024)