Synthesis of DOTA-Based 43Sc Radiopharmaceuticals Using Cyclotron-Produced 43Sc as Exemplified by [43Sc]Sc-PSMA-617 for PSMA PET Imaging

Meier, Jason P.; Bhuiyan, Mohammed; Freifelder, Richard; Zhang, Hannah J.; Gonzalez, Lucas; Pusateri, Antonino; Tsai, Hsiu-Ming; Leoni, Lara; Ghosh, Kaustab; Markiewicz, Erica; Henning, Christopher; Zhang, Yuhan; Weichselbaum, Ralph; Nolen, Jerry; Rotsch, David A.; Kao, Chien-Min; Szmulewitz, Russell Z.; Chen, Chin-Tu; Chitneni, Satish K.

doi:10.3390/mps8030058

Synthesis of DOTA-Based ⁴³Sc Radiopharmaceuticals Using Cyclotron-Produced ⁴³Sc as Exemplified by [⁴³Sc]Sc-PSMA-617 for PSMA PET Imaging

Journal Article · Wed Jun 04 00:00:00 EDT 2025 · Methods and Protocols

DOI:https://doi.org/10.3390/mps8030058· OSTI ID:2573247

^[1]; Bhuiyan, Mohammed ^[2]; Freifelder, Richard ^[3]; Zhang, Hannah J. ^[1]; Gonzalez, Lucas ^[1]; ^[1]; Tsai, Hsiu-Ming ^[1]; Leoni, Lara ^[4]; ^[1]; Markiewicz, Erica ^[1]; Henning, Christopher ^[1]; Zhang, Yuhan ^[1]; Weichselbaum, Ralph ^[3]; ^[3]; ^[5]; ^[3]; Szmulewitz, Russell Z. ^[3]; Chen, Chin-Tu ^[3]; ^[3]

Univ. of Chicago, IL (United States)
Univ. of Chicago, IL (United States); Univ. of Wisconsin, Madison, WI (United States)
Univ. of Chicago, IL (United States); Argonne National Laboratory (ANL), Argonne, IL (United States). Argonne Joint Radioisotope Initiative (JRI)
Univ. of Chicago, IL (United States); Northwestern Univ., Chicago, IL (United States)
Univ. of Chicago, IL (United States); Argonne National Laboratory (ANL), Argonne, IL (United States). Argonne Joint Radioisotope Initiative (JRI); Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

The implementation of theranostics in oncologic nuclear medicine has exhibited immense potential in improving patient outcomes in prostate cancer with the implementation of [⁶⁸Ga]Ga-PSMA-11 PET and [¹⁷⁷Lu]Lu-PSMA-617 into clinical practice. However, the correlation between radiopharmaceutical biodistributions seen with [⁶⁸Ga]Ga-PSMA-11 PET imaging and downstream [¹⁷⁷Lu]Lu-PSMA-617 therapy remains imperfect. This suggests that prostate cancer theranostics could potentially be further refined through the implementation of true theranostics, tandem pairs of diagnostic and therapeutic radiopharmaceuticals that utilize the same ligand and element, thus yielding identical pharmacokinetics. The radioscandiums are one such group of true theranostic radiopharmaceuticals. The radioscandiums consist of two β+ emitting scandium isotopes (⁴³Sc/⁴⁴Sc), as well as a β⁻ emitting therapeutic isotope (⁴⁷Sc), which can all conjugate with PSMA-targeting PSMA-617. This potential has led to extensive investigations into the production of the radioscandiums as well as pre-clinical assessments with several ligands; however, there is a lack of literature extensively describing the complete synthesis of scandium radiopharmaceuticals. which therefore limits the accessibility of radioscandium research in theranostics. As such, this work aims to present an easily translatable protocol for the synthesis of [⁴³Sc]Sc-PSMA-617 from a [⁴²Ca]CaCO₃ starting material, including target formation, nuclear production via ⁴²Ca(d,n)⁴³Sc reaction, chemical separation, radiolabeling, solvent reformulation, and target recycling.

View Accepted Manuscript (DOE)

Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE

Grant/Contract Number:: AC05-00OR22725

OSTI ID:: 2573247

Journal Information:: Methods and Protocols, Journal Name: Methods and Protocols Journal Issue: 3 Vol. 8; ISSN 2409-9279

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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Synthesis of DOTA-Based 43Sc Radiopharmaceuticals Using Cyclotron-Produced 43Sc as Exemplified by [43Sc]Sc-PSMA-617 for PSMA PET Imaging

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Synthesis of DOTA-Based ⁴³Sc Radiopharmaceuticals Using Cyclotron-Produced ⁴³Sc as Exemplified by [⁴³Sc]Sc-PSMA-617 for PSMA PET Imaging