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

doi:10.3390/molecules28166041

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

Molecules. 2023 Aug 13;28(16):6041. doi: 10.3390/molecules28166041.

Authors

Jason P Meier¹, Hannah J Zhang^{1

2}, Richard Freifelder^{1

3

4}, Mohammed Bhuiyan^{1

3}, Phillip Selman⁵, Megan Mendez⁵, Pavithra H A Kankanamalage^{6

7}, Thomas Brossard⁶, Antonino Pusateri¹, Hsiu-Ming Tsai², Lara Leoni², Sagada Penano¹, Kaustab Ghosh^{1

3}, Brittany A Broder^{1

8}, Erica Markiewicz², Amy Renne^{1

6}, Walter Stadler^{4

5}, Ralph Weichselbaum^{4

9}, Jerry Nolen^{4

6}, Chien-Min Kao^{1

2

4}, Satish K Chitneni¹, David A Rotsch^{4

6

10}, Russell Z Szmulewitz^{4

5}, Chin-Tu Chen^{1

2

3

4}

Affiliations

¹ Department of Radiology, The University of Chicago, Chicago, IL 60637, USA.
² Integrated Small Animal Imaging Research Resource, Office of Shared Research Facilities, The University of Chicago, Chicago, IL 60637, USA.
³ Cyclotron Facility, The University of Chicago, Chicago, IL 60637, USA.
⁴ UChicago/Argonne Joint Radioisotope Initiative (JRI), Chicago, IL 60637, USA.
⁵ Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
⁶ Physics Division, Argonne National Laboratory, Lemont, IL 60439, USA.
⁷ Collider Accelerator Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
⁸ National Institute of Standards and Technology, Gaithersburg, MD 20899, USA.
⁹ Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA.
¹⁰ Medical Isotope Development Group, Oak Ridge National Laboratory, Oak Ridge, TN 37830, USA.

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 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.

Keywords: PET; PSMA-617; SPECT; Scandium-43; Scandium-47; TRT; mCRPC; prostate cancer; radioisotopes; theranostics.

MeSH terms

Animals
Humans
Male
Mice
Nuclear Medicine*
Precision Medicine
Prostatic Neoplasms* / diagnostic imaging
Prostatic Neoplasms* / radiotherapy
Radioisotopes / therapeutic use
Scandium

Substances

Scandium
Radioisotopes

Abstract

MeSH terms

Substances

Grants and funding