Back to Search
Start Over
68 Ga-Labeled [Thz 14 ]Bombesin(7–14) Analogs: Promising GRPR-Targeting Agonist PET Tracers with Low Pancreas Uptake.
- Source :
- Molecules; Feb2023, Vol. 28 Issue 4, p1977, 15p
- Publication Year :
- 2023
-
Abstract
- With overexpression in various cancers, the gastrin-releasing peptide receptor (GRPR) is a promising target for cancer imaging and therapy. However, the high pancreas uptake of reported GRPR-targeting radioligands limits their clinical application. Our goal was to develop <superscript>68</superscript>Ga-labeled agonist tracers for detecting GRPR-expressing tumors with positron emission tomography (PET), and compare them with the clinically validated agonist PET tracer, [<superscript>68</superscript>Ga]Ga-AMBA. Ga-TacBOMB2, TacBOMB3, and TacBOMB4, derived from [Thz<superscript>14</superscript>]Bombesin(7–14), were confirmed to be GRPR agonists by a calcium mobilization study, and their binding affinities (K<subscript>i</subscript>(GRPR)) were determined to be 7.62 ± 0.19, 6.02 ± 0.59, and 590 ± 36.5 nM, respectively, via in vitro competition binding assays. [<superscript>68</superscript>Ga]Ga-TacBOMB2, [<superscript>68</superscript>Ga]Ga-TacBOMB3, and [<superscript>68</superscript>Ga]Ga-AMBA clearly visualized PC-3 tumor xenografts in a PET imaging study. [<superscript>68</superscript>Ga]Ga-TacBOMB2 showed comparable tumor uptake but superior tumor-to-background contrast ratios when compared to [<superscript>68</superscript>Ga]Ga-AMBA. Moreover, [<superscript>68</superscript>Ga]Ga-TacBOMB2 and [<superscript>68</superscript>Ga]Ga-TacBOMB3 showed a much lower rate of uptake in the pancreas (1.30 ± 0.14 and 2.41 ± 0.72%ID/g, respectively) than [<superscript>68</superscript>Ga]Ga-AMBA (62.4 ± 4.26%ID/g). In conclusion, replacing Met<superscript>14</superscript> in the GRPR-targeting sequence with Thz<superscript>14</superscript> retains high GRPR-binding affinity and agonist properties. With good tumor uptake and tumor-to-background uptake ratios, [<superscript>68</superscript>Ga]Ga-TacBOMB2 is promising for detecting GRPR-expressing tumors. The much lower pancreas uptake of [<superscript>68</superscript>Ga]Ga-TacBOMB2 and [<superscript>68</superscript>Ga]Ga-TacBOMB3 suggests that [Thz<superscript>14</superscript>]Bombesin(7–14) is a promising targeting vector for the design of GRPR-targeting radiopharmaceuticals, especially for radioligand therapy application. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 28
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- 162378439
- Full Text :
- https://doi.org/10.3390/molecules28041977