PET imaging of 52Mn labeled DOTATATE and DOTAJR11
Abstract Manganese-52 is gaining interest as an isotope for PET imaging due to its desirable decay and chemical properties for radiopharmaceutical development. Somatostatin receptor 2 (SSTR2) is significantly overexpressed by neuroendocrine tumors (NETs) and is an important target for nuclear imagin...
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2025-01-01
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| author | James M. Omweri Hailey A. Houson Shannon E. Lynch Volkan Tekin Anna G. Sorace Suzanne E. Lapi |
| author_facet | James M. Omweri Hailey A. Houson Shannon E. Lynch Volkan Tekin Anna G. Sorace Suzanne E. Lapi |
| author_sort | James M. Omweri |
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| description | Abstract Manganese-52 is gaining interest as an isotope for PET imaging due to its desirable decay and chemical properties for radiopharmaceutical development. Somatostatin receptor 2 (SSTR2) is significantly overexpressed by neuroendocrine tumors (NETs) and is an important target for nuclear imaging and therapy. As an agonist, [68Ga]Ga-DOTATATE has demonstrated significant internalization upon interaction with receptor ligands, whereas [68Ga]Ga-DOTA-JR11(as an antagonist) exhibits limited internalization but better pharmacokinetics and increased tumor uptake. The goal of this study was to label both DOTATATE and DOTA-JR11 peptides with 52Mn in high radiochemical yields (RCY) and sufficient specific activity. A comparison of these two compounds was performed in in vitro and in vivo studies in animals with somatostatin receptor-positive xenografts to characterize differences in cell, tumor, and tissue uptake. Radiolabeling of DOTATATE and DOTA-JR11 was carried out by combining varying concentrations of the peptides with [52Mn]MnCl2. In vitro stability of the radiotracers was determined in mouse serum. In vitro cell uptake and internalization assays were performed in SSTR2 + AR42J cells and negative controls. In vivo biodistribution and longitudinal PET imaging was evaluated in mice bearing AR42J tumors. Both [52Mn]Mn-DOTATATE and [52Mn]Mn-DOTA-JR11 showed affinity for SSTR2 in AR42J cells. However, the uptake of [52Mn]Mn-DOTATATE was higher (11.95 ± 0.71%/ mg) compared to [52Mn]Mn-DOTA-JR11 (7.31 ± 0.38%/ mg) after 2 h incubation. After 4 h incubation, 53.13 ± 1.83% of the total accumulated activity of [52Mn]Mn-DOTATATE was internalized, whereas only 20.85 ± 0.59% of the total accumulated activity of [52Mn]Mn-DOTA-JR11 was internalized. The PET images revealed similar biodistribution results, with [52Mn]Mn-DOTATATE showing a significant tumor uptake of 11.16 ± 2.97% ID/g, while [52Mn]Mn-DOTA-JR11 exhibited a lower tumor uptake of 2.11 ± 0.30% ID/g 4 h post-injection. The synthesis of both radiotracers was accomplished with high RCY and purity. The cell uptake and internalization of [52Mn]Mn-DOTATATE showed higher levels compared to [52Mn]Mn-DOTA-JR11. PET images of the radiotracers in AR42J tumor bearing mice demonstrated similar biodistribution in all organs except the tumor, with [52Mn]Mn-DOTATATE showing higher tumor uptake compared to [52Mn]Mn-DOTA-JR11. The variations in the properties of these tracers could be used to guide further imaging and treatment studies. |
| format | Article |
| id | doaj-art-4546874c87294fb0b596edee40906162 |
| institution | Kabale University |
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| spelling | doaj-art-4546874c87294fb0b596edee409061622025-01-19T12:24:33ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-025-85143-7PET imaging of 52Mn labeled DOTATATE and DOTAJR11James M. Omweri0Hailey A. Houson1Shannon E. Lynch2Volkan Tekin3Anna G. Sorace4Suzanne E. Lapi5Department of Radiology, The University of Alabama at BirminghamDepartment of Radiology, The University of Alabama at BirminghamDepartment of Radiology, The University of Alabama at BirminghamDepartment of Radiology, The University of Alabama at BirminghamDepartment of Radiology, The University of Alabama at BirminghamDepartment of Radiology, The University of Alabama at BirminghamAbstract Manganese-52 is gaining interest as an isotope for PET imaging due to its desirable decay and chemical properties for radiopharmaceutical development. Somatostatin receptor 2 (SSTR2) is significantly overexpressed by neuroendocrine tumors (NETs) and is an important target for nuclear imaging and therapy. As an agonist, [68Ga]Ga-DOTATATE has demonstrated significant internalization upon interaction with receptor ligands, whereas [68Ga]Ga-DOTA-JR11(as an antagonist) exhibits limited internalization but better pharmacokinetics and increased tumor uptake. The goal of this study was to label both DOTATATE and DOTA-JR11 peptides with 52Mn in high radiochemical yields (RCY) and sufficient specific activity. A comparison of these two compounds was performed in in vitro and in vivo studies in animals with somatostatin receptor-positive xenografts to characterize differences in cell, tumor, and tissue uptake. Radiolabeling of DOTATATE and DOTA-JR11 was carried out by combining varying concentrations of the peptides with [52Mn]MnCl2. In vitro stability of the radiotracers was determined in mouse serum. In vitro cell uptake and internalization assays were performed in SSTR2 + AR42J cells and negative controls. In vivo biodistribution and longitudinal PET imaging was evaluated in mice bearing AR42J tumors. Both [52Mn]Mn-DOTATATE and [52Mn]Mn-DOTA-JR11 showed affinity for SSTR2 in AR42J cells. However, the uptake of [52Mn]Mn-DOTATATE was higher (11.95 ± 0.71%/ mg) compared to [52Mn]Mn-DOTA-JR11 (7.31 ± 0.38%/ mg) after 2 h incubation. After 4 h incubation, 53.13 ± 1.83% of the total accumulated activity of [52Mn]Mn-DOTATATE was internalized, whereas only 20.85 ± 0.59% of the total accumulated activity of [52Mn]Mn-DOTA-JR11 was internalized. The PET images revealed similar biodistribution results, with [52Mn]Mn-DOTATATE showing a significant tumor uptake of 11.16 ± 2.97% ID/g, while [52Mn]Mn-DOTA-JR11 exhibited a lower tumor uptake of 2.11 ± 0.30% ID/g 4 h post-injection. The synthesis of both radiotracers was accomplished with high RCY and purity. The cell uptake and internalization of [52Mn]Mn-DOTATATE showed higher levels compared to [52Mn]Mn-DOTA-JR11. PET images of the radiotracers in AR42J tumor bearing mice demonstrated similar biodistribution in all organs except the tumor, with [52Mn]Mn-DOTATATE showing higher tumor uptake compared to [52Mn]Mn-DOTA-JR11. The variations in the properties of these tracers could be used to guide further imaging and treatment studies.https://doi.org/10.1038/s41598-025-85143-7Agonists/antagonistsPeptidesAR42JManganese-52SSTR2 |
| spellingShingle | James M. Omweri Hailey A. Houson Shannon E. Lynch Volkan Tekin Anna G. Sorace Suzanne E. Lapi PET imaging of 52Mn labeled DOTATATE and DOTAJR11 Scientific Reports Agonists/antagonists Peptides AR42J Manganese-52 SSTR2 |
| title | PET imaging of 52Mn labeled DOTATATE and DOTAJR11 |
| title_full | PET imaging of 52Mn labeled DOTATATE and DOTAJR11 |
| title_fullStr | PET imaging of 52Mn labeled DOTATATE and DOTAJR11 |
| title_full_unstemmed | PET imaging of 52Mn labeled DOTATATE and DOTAJR11 |
| title_short | PET imaging of 52Mn labeled DOTATATE and DOTAJR11 |
| title_sort | pet imaging of 52mn labeled dotatate and dotajr11 |
| topic | Agonists/antagonists Peptides AR42J Manganese-52 SSTR2 |
| url | https://doi.org/10.1038/s41598-025-85143-7 |
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