<sup>68</sup>Ga-Labeled [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14) Derivatives: Promising GRPR-Targeting PET Tracers with Low Pancreas Uptake
The gastrin-releasing peptide receptor (GRPR) is a G-protein-coupled receptor that is overexpressed in many solid cancers and is a promising target for cancer imaging and therapy. However, high pancreas uptake is a major concern in the application of reported GRPR-targeting radiopharmaceuticals, par...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/12/3777 |
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| author | Lei Wang Zhengxing Zhang Helen Merkens Jutta Zeisler Chengcheng Zhang Aron Roxin Ruiyan Tan François Bénard Kuo-Shyan Lin |
| author_facet | Lei Wang Zhengxing Zhang Helen Merkens Jutta Zeisler Chengcheng Zhang Aron Roxin Ruiyan Tan François Bénard Kuo-Shyan Lin |
| author_sort | Lei Wang |
| collection | DOAJ |
| description | The gastrin-releasing peptide receptor (GRPR) is a G-protein-coupled receptor that is overexpressed in many solid cancers and is a promising target for cancer imaging and therapy. However, high pancreas uptake is a major concern in the application of reported GRPR-targeting radiopharmaceuticals, particularly for targeted radioligand therapy. To lower pancreas uptake, we explored Ga-complexed TacsBOMB2, TacsBOMB3, TacsBOMB4, TacsBOMB5, and TacsBOMB6 derived from a potent GRPR antagonist sequence, [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14), and compared their potential for cancer imaging with [<sup>68</sup>Ga]Ga-RM2. The K<sub>i</sub>(GRPR) values of Ga-TacsBOMB2, Ga-TacsBOMB3, Ga-TacsBOMB4, Ga-TacsBOMB5, Ga-TacsBOMB6, and Ga-RM2 were 7.08 ± 0.65, 4.29 ± 0.46, 458 ± 38.6, 6.09 ± 0.95, 5.12 ± 0.57, and 1.51 ± 0.24 nM, respectively. [<sup>68</sup>Ga]Ga-TacsBOMB2, [<sup>68</sup>Ga]Ga-TacsBOMB3, [<sup>68</sup>Ga]Ga-TacsBOMB5, [<sup>68</sup>Ga]Ga-TacsBOMB6, and [<sup>68</sup>Ga]Ga-RM2 clearly show PC-3 tumor xenografts in positron emission tomography (PET) images, while [<sup>68</sup>Ga]Ga-TacsBOMB5 shows the highest tumor uptake (15.7 ± 2.17 %ID/g) among them. Most importantly, the pancreas uptake values of [<sup>68</sup>Ga]Ga-TacsBOMB2 (2.81 ± 0.78 %ID/g), [<sup>68</sup>Ga]Ga-TacsBOMB3 (7.26 ± 1.00 %ID/g), [<sup>68</sup>Ga]Ga-TacsBOMB5 (1.98 ± 0.10 %ID/g), and [<sup>68</sup>Ga]Ga-TacsBOMB6 (6.50 ± 0.36 %ID/g) were much lower than the value of [<sup>68</sup>Ga]Ga-RM2 (41.9 ± 10.1 %ID/g). Among the tested [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14) derivatives, [<sup>68</sup>Ga]Ga-TacsBOMB5 has the highest tumor uptake and tumor-to-background contrast ratios, which is promising for clinical translation to detect GRPR-expressing tumors. Due to the low pancreas uptake of its derivatives, [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14) represents a promising pharmacophore for the design of GRPR-targeting radiopharmaceuticals, especially for targeted radioligand therapy application. |
| first_indexed | 2024-03-09T22:55:59Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T22:55:59Z |
| publishDate | 2022-06-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-3402a555c63a425d907e62d487c003b12023-11-23T18:11:08ZengMDPI AGMolecules1420-30492022-06-012712377710.3390/molecules27123777<sup>68</sup>Ga-Labeled [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14) Derivatives: Promising GRPR-Targeting PET Tracers with Low Pancreas UptakeLei Wang0Zhengxing Zhang1Helen Merkens2Jutta Zeisler3Chengcheng Zhang4Aron Roxin5Ruiyan Tan6François Bénard7Kuo-Shyan Lin8Department of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 1L3, CanadaDepartment of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 1L3, CanadaDepartment of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 1L3, CanadaDepartment of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 1L3, CanadaDepartment of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 1L3, CanadaDepartment of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 1L3, CanadaDepartment of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 1L3, CanadaDepartment of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 1L3, CanadaDepartment of Molecular Oncology, BC Cancer, Vancouver, BC V5Z 1L3, CanadaThe gastrin-releasing peptide receptor (GRPR) is a G-protein-coupled receptor that is overexpressed in many solid cancers and is a promising target for cancer imaging and therapy. However, high pancreas uptake is a major concern in the application of reported GRPR-targeting radiopharmaceuticals, particularly for targeted radioligand therapy. To lower pancreas uptake, we explored Ga-complexed TacsBOMB2, TacsBOMB3, TacsBOMB4, TacsBOMB5, and TacsBOMB6 derived from a potent GRPR antagonist sequence, [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14), and compared their potential for cancer imaging with [<sup>68</sup>Ga]Ga-RM2. The K<sub>i</sub>(GRPR) values of Ga-TacsBOMB2, Ga-TacsBOMB3, Ga-TacsBOMB4, Ga-TacsBOMB5, Ga-TacsBOMB6, and Ga-RM2 were 7.08 ± 0.65, 4.29 ± 0.46, 458 ± 38.6, 6.09 ± 0.95, 5.12 ± 0.57, and 1.51 ± 0.24 nM, respectively. [<sup>68</sup>Ga]Ga-TacsBOMB2, [<sup>68</sup>Ga]Ga-TacsBOMB3, [<sup>68</sup>Ga]Ga-TacsBOMB5, [<sup>68</sup>Ga]Ga-TacsBOMB6, and [<sup>68</sup>Ga]Ga-RM2 clearly show PC-3 tumor xenografts in positron emission tomography (PET) images, while [<sup>68</sup>Ga]Ga-TacsBOMB5 shows the highest tumor uptake (15.7 ± 2.17 %ID/g) among them. Most importantly, the pancreas uptake values of [<sup>68</sup>Ga]Ga-TacsBOMB2 (2.81 ± 0.78 %ID/g), [<sup>68</sup>Ga]Ga-TacsBOMB3 (7.26 ± 1.00 %ID/g), [<sup>68</sup>Ga]Ga-TacsBOMB5 (1.98 ± 0.10 %ID/g), and [<sup>68</sup>Ga]Ga-TacsBOMB6 (6.50 ± 0.36 %ID/g) were much lower than the value of [<sup>68</sup>Ga]Ga-RM2 (41.9 ± 10.1 %ID/g). Among the tested [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14) derivatives, [<sup>68</sup>Ga]Ga-TacsBOMB5 has the highest tumor uptake and tumor-to-background contrast ratios, which is promising for clinical translation to detect GRPR-expressing tumors. Due to the low pancreas uptake of its derivatives, [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14) represents a promising pharmacophore for the design of GRPR-targeting radiopharmaceuticals, especially for targeted radioligand therapy application.https://www.mdpi.com/1420-3049/27/12/3777gastrin-releasing peptide receptorpositron-emission tomographygallium-68pancreas uptake |
| spellingShingle | Lei Wang Zhengxing Zhang Helen Merkens Jutta Zeisler Chengcheng Zhang Aron Roxin Ruiyan Tan François Bénard Kuo-Shyan Lin <sup>68</sup>Ga-Labeled [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14) Derivatives: Promising GRPR-Targeting PET Tracers with Low Pancreas Uptake Molecules gastrin-releasing peptide receptor positron-emission tomography gallium-68 pancreas uptake |
| title | <sup>68</sup>Ga-Labeled [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14) Derivatives: Promising GRPR-Targeting PET Tracers with Low Pancreas Uptake |
| title_full | <sup>68</sup>Ga-Labeled [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14) Derivatives: Promising GRPR-Targeting PET Tracers with Low Pancreas Uptake |
| title_fullStr | <sup>68</sup>Ga-Labeled [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14) Derivatives: Promising GRPR-Targeting PET Tracers with Low Pancreas Uptake |
| title_full_unstemmed | <sup>68</sup>Ga-Labeled [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14) Derivatives: Promising GRPR-Targeting PET Tracers with Low Pancreas Uptake |
| title_short | <sup>68</sup>Ga-Labeled [Leu<sup>13</sup>ψThz<sup>14</sup>]Bombesin(7–14) Derivatives: Promising GRPR-Targeting PET Tracers with Low Pancreas Uptake |
| title_sort | sup 68 sup ga labeled leu sup 13 sup ψthz sup 14 sup bombesin 7 14 derivatives promising grpr targeting pet tracers with low pancreas uptake |
| topic | gastrin-releasing peptide receptor positron-emission tomography gallium-68 pancreas uptake |
| url | https://www.mdpi.com/1420-3049/27/12/3777 |
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