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

The implementation of theranostics in oncologic nuclear medicine has exhibited immense potential in improving patient outcomes in prostate cancer with the implementation of [<sup>68</sup>Ga]Ga-PSMA-11 PET and [<sup>177</sup>Lu]Lu-PSMA-617 into clinical practice. However, the...

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Main Authors: Jason P. Meier, Mohammed Bhuiyan, Richard Freifelder, Hannah J. Zhang, Lucas Gonzalez, Antonino Pusateri, Hsiu-Ming Tsai, Lara Leoni, Kaustab Ghosh, Erica Markiewicz, Christopher Henning, Yuhan Zhang, Ralph Weichselbaum, Jerry Nolen, David A. Rotsch, Chien-Min Kao, Russell Z. Szmulewitz, Chin-Tu Chen, Satish K. Chitneni
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Language:English
Published: MDPI AG 2025-06-01
Series:Methods and Protocols
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Online Access:https://www.mdpi.com/2409-9279/8/3/58
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author Jason P. Meier
Mohammed Bhuiyan
Richard Freifelder
Hannah J. Zhang
Lucas Gonzalez
Antonino Pusateri
Hsiu-Ming Tsai
Lara Leoni
Kaustab Ghosh
Erica Markiewicz
Christopher Henning
Yuhan Zhang
Ralph Weichselbaum
Jerry Nolen
David A. Rotsch
Chien-Min Kao
Russell Z. Szmulewitz
Chin-Tu Chen
Satish K. Chitneni
author_facet Jason P. Meier
Mohammed Bhuiyan
Richard Freifelder
Hannah J. Zhang
Lucas Gonzalez
Antonino Pusateri
Hsiu-Ming Tsai
Lara Leoni
Kaustab Ghosh
Erica Markiewicz
Christopher Henning
Yuhan Zhang
Ralph Weichselbaum
Jerry Nolen
David A. Rotsch
Chien-Min Kao
Russell Z. Szmulewitz
Chin-Tu Chen
Satish K. Chitneni
author_sort Jason P. Meier
collection DOAJ
description The implementation of theranostics in oncologic nuclear medicine has exhibited immense potential in improving patient outcomes in prostate cancer with the implementation of [<sup>68</sup>Ga]Ga-PSMA-11 PET and [<sup>177</sup>Lu]Lu-PSMA-617 into clinical practice. However, the correlation between radiopharmaceutical biodistributions seen with [<sup>68</sup>Ga]Ga-PSMA-11 PET imaging and downstream [<sup>177</sup>Lu]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 (<sup>43</sup>Sc/<sup>44</sup>Sc), as well as a β<sup>−</sup> emitting therapeutic isotope (<sup>47</sup>Sc), 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 [<sup>43</sup>Sc]Sc-PSMA-617 from a [<sup>42</sup>Ca]CaCO<sub>3</sub> starting material, including target formation, nuclear production via <sup>42</sup>Ca(d,n)<sup>43</sup>Sc reaction, chemical separation, radiolabeling, solvent reformulation, and target recycling.
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spelling doaj-art-a842e8620acd49fc9aad33e4237ad5402025-08-20T03:27:32ZengMDPI AGMethods and Protocols2409-92792025-06-01835810.3390/mps8030058Synthesis of DOTA-Based <sup>43</sup>Sc Radiopharmaceuticals Using Cyclotron-Produced <sup>43</sup>Sc as Exemplified by [<sup>43</sup>Sc]Sc-PSMA-617 for PSMA PET ImagingJason P. Meier0Mohammed Bhuiyan1Richard Freifelder2Hannah J. Zhang3Lucas Gonzalez4Antonino Pusateri5Hsiu-Ming Tsai6Lara Leoni7Kaustab Ghosh8Erica Markiewicz9Christopher Henning10Yuhan Zhang11Ralph Weichselbaum12Jerry Nolen13David A. Rotsch14Chien-Min Kao15Russell Z. Szmulewitz16Chin-Tu Chen17Satish K. Chitneni18Department of Radiology, The University of Chicago, Chicago, IL 60637, USADepartment of Radiology, The University of Chicago, Chicago, IL 60637, USADepartment of Radiology, The University of Chicago, Chicago, IL 60637, USADepartment of Radiology, The University of Chicago, Chicago, IL 60637, USADepartment of Radiology, The University of Chicago, Chicago, IL 60637, USADepartment of Radiology, The University of Chicago, Chicago, IL 60637, USAIntegrated Small Animal Imaging Research Resource, Office of Shared Research Facilities, The University of Chicago, Chicago, IL 60637, USAIntegrated Small Animal Imaging Research Resource, Office of Shared Research Facilities, The University of Chicago, Chicago, IL 60637, USADepartment of Radiology, The University of Chicago, Chicago, IL 60637, USAIntegrated Small Animal Imaging Research Resource, Office of Shared Research Facilities, The University of Chicago, Chicago, IL 60637, USADepartment of Medicine, The University of Chicago, Chicago, IL 60637, USADepartment of Medicine, The University of Chicago, Chicago, IL 60637, USAUChicago/Argonne Joint Radioisotope Initiative (JRI), Chicago, IL 60637, USAUChicago/Argonne Joint Radioisotope Initiative (JRI), Chicago, IL 60637, USAUChicago/Argonne Joint Radioisotope Initiative (JRI), Chicago, IL 60637, USADepartment of Radiology, The University of Chicago, Chicago, IL 60637, USAUChicago/Argonne Joint Radioisotope Initiative (JRI), Chicago, IL 60637, USADepartment of Radiology, The University of Chicago, Chicago, IL 60637, USADepartment of Radiology, The University of Chicago, Chicago, IL 60637, USAThe implementation of theranostics in oncologic nuclear medicine has exhibited immense potential in improving patient outcomes in prostate cancer with the implementation of [<sup>68</sup>Ga]Ga-PSMA-11 PET and [<sup>177</sup>Lu]Lu-PSMA-617 into clinical practice. However, the correlation between radiopharmaceutical biodistributions seen with [<sup>68</sup>Ga]Ga-PSMA-11 PET imaging and downstream [<sup>177</sup>Lu]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 (<sup>43</sup>Sc/<sup>44</sup>Sc), as well as a β<sup>−</sup> emitting therapeutic isotope (<sup>47</sup>Sc), 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 [<sup>43</sup>Sc]Sc-PSMA-617 from a [<sup>42</sup>Ca]CaCO<sub>3</sub> starting material, including target formation, nuclear production via <sup>42</sup>Ca(d,n)<sup>43</sup>Sc reaction, chemical separation, radiolabeling, solvent reformulation, and target recycling.https://www.mdpi.com/2409-9279/8/3/58theranosticsScandium-43Scandium-44Scandium-47PSMA-617prostate cancer
spellingShingle Jason P. Meier
Mohammed Bhuiyan
Richard Freifelder
Hannah J. Zhang
Lucas Gonzalez
Antonino Pusateri
Hsiu-Ming Tsai
Lara Leoni
Kaustab Ghosh
Erica Markiewicz
Christopher Henning
Yuhan Zhang
Ralph Weichselbaum
Jerry Nolen
David A. Rotsch
Chien-Min Kao
Russell Z. Szmulewitz
Chin-Tu Chen
Satish K. Chitneni
Synthesis of DOTA-Based <sup>43</sup>Sc Radiopharmaceuticals Using Cyclotron-Produced <sup>43</sup>Sc as Exemplified by [<sup>43</sup>Sc]Sc-PSMA-617 for PSMA PET Imaging
Methods and Protocols
theranostics
Scandium-43
Scandium-44
Scandium-47
PSMA-617
prostate cancer
title Synthesis of DOTA-Based <sup>43</sup>Sc Radiopharmaceuticals Using Cyclotron-Produced <sup>43</sup>Sc as Exemplified by [<sup>43</sup>Sc]Sc-PSMA-617 for PSMA PET Imaging
title_full Synthesis of DOTA-Based <sup>43</sup>Sc Radiopharmaceuticals Using Cyclotron-Produced <sup>43</sup>Sc as Exemplified by [<sup>43</sup>Sc]Sc-PSMA-617 for PSMA PET Imaging
title_fullStr Synthesis of DOTA-Based <sup>43</sup>Sc Radiopharmaceuticals Using Cyclotron-Produced <sup>43</sup>Sc as Exemplified by [<sup>43</sup>Sc]Sc-PSMA-617 for PSMA PET Imaging
title_full_unstemmed Synthesis of DOTA-Based <sup>43</sup>Sc Radiopharmaceuticals Using Cyclotron-Produced <sup>43</sup>Sc as Exemplified by [<sup>43</sup>Sc]Sc-PSMA-617 for PSMA PET Imaging
title_short Synthesis of DOTA-Based <sup>43</sup>Sc Radiopharmaceuticals Using Cyclotron-Produced <sup>43</sup>Sc as Exemplified by [<sup>43</sup>Sc]Sc-PSMA-617 for PSMA PET Imaging
title_sort synthesis of dota based sup 43 sup sc radiopharmaceuticals using cyclotron produced sup 43 sup sc as exemplified by sup 43 sup sc sc psma 617 for psma pet imaging
topic theranostics
Scandium-43
Scandium-44
Scandium-47
PSMA-617
prostate cancer
url https://www.mdpi.com/2409-9279/8/3/58
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