PET Probes for Preclinical Imaging of GRPR-Positive Prostate Cancer: Comparative Preclinical Study of [68Ga]Ga-NODAGA-AMBA and [44Sc]Sc-NODAGA-AMBA
Abstract
:1. Introduction
2. Results
2.1. Radiochemistry
2.2. LogP and Serum Stability Measurements
2.3. In Vitro Cellular Uptake Studies
2.4. Biodistribution and Pharmacokinetic Studies in Healthy Mice
2.5. PET Imaging and Ex Vivo Biodistribution Studies of PC-3 Tumor-Bearing Mice
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. 68Ga-Labelling of NODAGA-AMBA
4.3. 44Sc-Labelling of NODAGA-AMBA
4.4. Determination of Partition Coefficient and Metabolic Stability of 68Ga- and 44Sc-Labelled NODAGA-AMBA
4.5. Cell Lines
4.6. Cellular Uptake Studies
4.7. In Vivo Tumor Model
4.8. In Vivo PET Imaging
4.9. Ex Vivo Biodistribution Studies
4.10. Pharmacokinetic Studies and In Vivo Stability
4.11. Blocking Experiments
4.12. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AMBA | aminobenzoic-acid |
AR | androgen receptor |
BBN | bombesin |
BB2 | bombesin type 2 receptor |
BFC | bifunctional chelator |
DOTA | tetraazacyclododecane-tetrayl-tetraacetic acid |
DTPA | diethylenetriamine-pentaacetic acid |
18F-FCH | 18F-fluorocholine |
GRP | gastrin-releasing peptide |
GRPR | gastrin-releasing peptide receptor |
NET | neuroendocrine |
NODAGA | aminoethylamino-carboxy-oxobutyl-triazonane-diyldiacetic acid |
NOTA | triazacyclononane-triyl-triacetic acid |
PCa | prostate cancer |
PET | positron emission tomography |
SUV | standardized uptake values |
T/M | Tumor-to-muscle |
VOI | volumes of interest |
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Tumor | [68Ga]Ga-NODAGA-AMBA | [44Sc]Sc-NODAGA-AMBA | ||
---|---|---|---|---|
60 min | 120 min | 60 min | 120 min | |
PC3 | 3.78 ± 0.93 ** | 3.29 ± 1.20 ** | 4.56 ± 0.45 ** | 4.14 ± 0.47 ** |
PC3 blocked | 0.60 ± 0.22 | 0.48 ± 0.14 | 0.79 ± 0.16 | 0.69 ± 0.17 |
PC3 T/M | 13.21 ± 2.47 ** | 21.64 ± 3.78 ** | 16.88 ± 1.96 ** | 27.57 ± 2.88 ** |
PC3 T/M blocked | 1.97 ± 0.22 | 2.86 ± 0.47 | 2.19 ± 0.36 | 3.04 ± 0.62 |
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Kálmán-Szabó, I.; Szabó, J.P.; Arató, V.; Dénes, N.; Opposits, G.; Jószai, I.; Kertész, I.; Képes, Z.; Fekete, A.; Szikra, D.; et al. PET Probes for Preclinical Imaging of GRPR-Positive Prostate Cancer: Comparative Preclinical Study of [68Ga]Ga-NODAGA-AMBA and [44Sc]Sc-NODAGA-AMBA. Int. J. Mol. Sci. 2022, 23, 10061. https://doi.org/10.3390/ijms231710061
Kálmán-Szabó I, Szabó JP, Arató V, Dénes N, Opposits G, Jószai I, Kertész I, Képes Z, Fekete A, Szikra D, et al. PET Probes for Preclinical Imaging of GRPR-Positive Prostate Cancer: Comparative Preclinical Study of [68Ga]Ga-NODAGA-AMBA and [44Sc]Sc-NODAGA-AMBA. International Journal of Molecular Sciences. 2022; 23(17):10061. https://doi.org/10.3390/ijms231710061
Chicago/Turabian StyleKálmán-Szabó, Ibolya, Judit P. Szabó, Viktória Arató, Noémi Dénes, Gábor Opposits, István Jószai, István Kertész, Zita Képes, Anikó Fekete, Dezső Szikra, and et al. 2022. "PET Probes for Preclinical Imaging of GRPR-Positive Prostate Cancer: Comparative Preclinical Study of [68Ga]Ga-NODAGA-AMBA and [44Sc]Sc-NODAGA-AMBA" International Journal of Molecular Sciences 23, no. 17: 10061. https://doi.org/10.3390/ijms231710061