Accelerator-Based Production of Scandium Radioisotopes for Applications in Prostate Cancer: Toward Building a Pipeline for Rapid Development of Novel Theranostics
Jason P. Meier,
Hannah J. Zhang,
Richard Freifelder,
Mohammed Bhuiyan,
Phillip Selman,
Megan Mendez,
Pavithra H. A. Kankanamalage,
Thomas Brossard,
Antonino Pusateri,
Hsiu-Ming Tsai,
Lara Leoni,
Sagada Penano,
Kaustab Ghosh,
Brittany A. Broder,
Erica Markiewicz,
Amy Renne,
Walter Stadler,
Ralph Weichselbaum,
Jerry Nolen,
Chien-Min Kao,
Satish K. Chitneni,
David A. Rotsch,
Russell Z. Szmulewitz,
Chin-Tu Chen
Affiliations
Jason P. Meier
Department of Radiology, The University of Chicago, Chicago, IL 60637, USA
Hannah J. Zhang
Department of Radiology, The University of Chicago, Chicago, IL 60637, USA
Richard Freifelder
Department of Radiology, The University of Chicago, Chicago, IL 60637, USA
Mohammed Bhuiyan
Department of Radiology, The University of Chicago, Chicago, IL 60637, USA
Phillip Selman
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Megan Mendez
Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
Pavithra H. A. Kankanamalage
Physics Division, Argonne National Laboratory, Lemont, IL 60439, USA
Thomas Brossard
Physics Division, Argonne National Laboratory, Lemont, IL 60439, USA
Antonino Pusateri
Department of Radiology, The University of Chicago, Chicago, IL 60637, USA
Hsiu-Ming Tsai
Integrated Small Animal Imaging Research Resource, Office of Shared Research Facilities, The University of Chicago, Chicago, IL 60637, USA
Lara Leoni
Integrated Small Animal Imaging Research Resource, Office of Shared Research Facilities, The University of Chicago, Chicago, IL 60637, USA
Sagada Penano
Department of Radiology, The University of Chicago, Chicago, IL 60637, USA
Kaustab Ghosh
Department of Radiology, The University of Chicago, Chicago, IL 60637, USA
Brittany A. Broder
Department of Radiology, The University of Chicago, Chicago, IL 60637, USA
Erica Markiewicz
Integrated Small Animal Imaging Research Resource, Office of Shared Research Facilities, The University of Chicago, Chicago, IL 60637, USA
Amy Renne
Department of Radiology, The University of Chicago, Chicago, IL 60637, USA
Walter Stadler
UChicago/Argonne Joint Radioisotope Initiative (JRI), Chicago, IL 60637, USA
Ralph Weichselbaum
UChicago/Argonne Joint Radioisotope Initiative (JRI), Chicago, IL 60637, USA
Jerry Nolen
UChicago/Argonne Joint Radioisotope Initiative (JRI), Chicago, IL 60637, USA
Chien-Min Kao
Department of Radiology, The University of Chicago, Chicago, IL 60637, USA
Satish K. Chitneni
Department of Radiology, The University of Chicago, Chicago, IL 60637, USA
David A. Rotsch
UChicago/Argonne Joint Radioisotope Initiative (JRI), Chicago, IL 60637, USA
Russell Z. Szmulewitz
UChicago/Argonne Joint Radioisotope Initiative (JRI), Chicago, IL 60637, USA
Chin-Tu Chen
Department of Radiology, The University of Chicago, Chicago, IL 60637, USA
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 favorable decay schema and shared pharmacokinetics as a true theranostic pair. Additionally, 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 for other proposed true theranostics. Before 43/47Sc can see widespread pre-clinical evaluation, however, an accessible production methodology must be established 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 cyclotron to support solid targets and produce 43Sc via the 42Ca(d,n)43Sc reaction has been devised, 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 are also presented.
