Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine
Abstract
:1. Introduction
2. Results
2.1. Establishment of FAPI1 to 5
2.2. Comparison of Cellular Uptake between FAPI1 to 5
2.3. Comparison of Body Distributions of FAPI1 or FAPI5 between Two Nuclides
2.4. Comparison of Anti-Tumor Effects due to Differences in Linker
3. Discussion
4. Materials and Methods
4.1. Synthesis of 211At-FAPI Compounds
4.2. Synthesis of 131I-FAPI Compounds
4.3. In Vitro Cellular Uptake Analysis
4.4. Preparation of Animals
4.5. Measurement of Biodistribution of FAP1 and FAPI5 Labeled with 131I or 211At
4.5.1. Biodistribution of 131I-FAPI1 and 131I-FAPI5
4.5.2. Biodistribution of 211At-FAPI1 and 211At-FAPI5
4.6. Examination of Therapeutic Effect
4.7. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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(a) 1 h | (b) 3 h | ||||
---|---|---|---|---|---|
131I-FAPI1 | 131I-FAPI5 | 131I-FAPI1 | 131I-FAPI5 | ||
Brain | 0.54 ± 0.15 | 0.50 ± 0.10 | Brain | 0.34 ± 0.04 | 0.30 ± 0.02 |
Thyroid | 7.96 ± 1.99 | 5.66 ± 0.26 | Thyroid | 12.86 ± 0.68 * | 8.40 ± 0.70 |
Salivary gland | 2.32 ± 0.12 | 2.65 ± 0.36 | Salivary gland | 1.72 ± 0.30 | 1.82 ± 0.11 |
Heart | 1.33 ± 0.06 | 1.21 ± 0.07 | Heart | 0.91 ± 0.12 | 1.95 ± 0.06 |
Lung | 3.82 ± 2.11 | 4.43 ± 2.34 | Lung | 2.15 ± 0.47 | 2.33 ± 0.38 |
Liver | 7.02 ± 0.90 | 7.40 ± 0.71 | Liver | 3.02 ± 0.70 | 2.85 ± 0.29 |
Stomach | 7.67 ± 3.50 | 7.75 ± 4.99 | Stomach | 2.57 ± 0.66 | 2.10 ± 0.84 |
Small Intestine | 48.18 ± 23.44 | 38.53 ± 17.18 | Small Intestine | 5.99 ± 1.91 | 5.54 ± 1.90 |
Colon | 9.63 ± 1.69 | 10.43 ± 1.67 | Colon | 155.39 ± 16.65 | 165.96 ± 15.26 |
Kidney | 3.68 ± 0.26 | 3.92 ± 0.41 | Kidney | 1.74 ± 0.12 | 1.74 ± 0.08 |
Pancreas | 1.54 ± 0.18 | 1.58 ± 0.30 | Pancreas | 0.63 ± 0.12 | 0.79 ± 0.12 |
Spleen | 1.42 ± 0.42 | 1.15 ± 0.06 | Spleen | 0.54 ± 0.17 | 0.64 ± 0.05 |
Testis | 0.56 ± 0.04 | 0.66 ± 0.08 | Testis | 0.76 ± 0.13 | 0.64 ± 0.08 |
Blood | 1.99 ± 0.20 | 2.36 ± 0.17 | Blood | 2.86 ± 0.46 | 2.32 ± 0.19 |
Bone | 0.47 ± 0.07 | 0.68 ± 0.09 | Bone | 0.37 ± 0.07 | 0.40 ± 0.01 |
Tumor | 0.77 ± 0.31 | 1.13 ± 0.10 | Tumor | 0.89 ± 0.44 | 1.13 ± 0.07 |
(a) 1 h | (b) 3 h | ||||
---|---|---|---|---|---|
211At-FAPI1 | 211At-FAPI5 | 211At-FAPI1 | 211At-FAPI5 | ||
Brain | 0.38 ± 0.04 | 0.30 ± 0.05 | Brain | 0.20 ± 0.04 | 0.30 ± 0.07 |
Thyroid | 3.73 ± 0.57 | 3.58 ± 0.71 | Thyroid | 16.12 ± 5.84 | 24.33 ± 6.86 |
Salivary gland | 4.18 ± 0.72 | 3.27 ± 0.38 | Salivary gland | 8.51 ± 2.25 | 6.43 ± 3.55 |
Heart | 3.24 ± 0.17 * | 1.51 ± 0.14 | Heart | 2.21 ± 0.13 | 0.90 ± 0.63 |
Lung | 4.61 ± 0.68 | 2.86 ± 0.24 | Lung | 4.92 ± 1.39 | 3.28 ± 1.95 |
Liver | 17.06 ± 0.98 * | 6.46 ± 0.62 | Liver | 1.77 ± 0.44 | 0.50 ± 0.61 |
Stomach | 19.31 ± 1.21 | 14.33 ± 3.00 | Stomach | 9.30 ± 1.27 * | 1.85 ± 1.70 |
Small Intestine | 33.16 ± 3.61 | 28.20 ± 5.27 | Small Intestine | 4.85 ± 1.28 | 4.89 ± 3.82 |
Colon | 6.34 ± 0.35 | 4.29 ± 0.44 | Colon | 32.44 ± 14.99 | 58.40 ± 9.91 |
Kidney | 6.92 ± 1.34 * | 3.07 ± 0.07 | Kidney | 2.22 ± 0.24 | 1.56 ± 0.81 |
Pancreas | 1.43 ± 0.16 | 1.17 ± 0.12 | Pancreas | 0.63 ± 0.05 | 0.45 ± 0.29 |
Spleen | 3.93 ± 0.52 | 2.58 ± 0.51 | Spleen | 5.27 ± 1.11 | 4.32 ± 0.21 |
Testis | 1.19 ± 0.10 | 1.05 ± 0.07 | Testis | 1.51 ± 0.28 | 1.95 ± 0.46 |
Blood | 3.76 ± 2.69 | 1.32 ± 0.04 | Blood | 1.20 ± 0.11 | 1.33 ± 0.24 |
Bone | 1.07 ± 0.12 | 0.61 ± 0.13 | Bone | 0.70 ± 0.14 | 1.35 ± 0.51 |
Tumor | 2.15 ± 0.24 * | 1.24 ± 0.14 | Tumor | 3.04 ± 0.69 * | 1.48 ± 0.89 |
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Aso, A.; Nabetani, H.; Matsuura, Y.; Kadonaga, Y.; Shirakami, Y.; Watabe, T.; Yoshiya, T.; Mochizuki, M.; Ooe, K.; Kawakami, A.; et al. Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine. Int. J. Mol. Sci. 2023, 24, 8701. https://doi.org/10.3390/ijms24108701
Aso A, Nabetani H, Matsuura Y, Kadonaga Y, Shirakami Y, Watabe T, Yoshiya T, Mochizuki M, Ooe K, Kawakami A, et al. Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine. International Journal of Molecular Sciences. 2023; 24(10):8701. https://doi.org/10.3390/ijms24108701
Chicago/Turabian StyleAso, Ayaka, Hinako Nabetani, Yoshifumi Matsuura, Yuichiro Kadonaga, Yoshifumi Shirakami, Tadashi Watabe, Taku Yoshiya, Masayoshi Mochizuki, Kazuhiro Ooe, Atsuko Kawakami, and et al. 2023. "Evaluation of Astatine-211-Labeled Fibroblast Activation Protein Inhibitor (FAPI): Comparison of Different Linkers with Polyethylene Glycol and Piperazine" International Journal of Molecular Sciences 24, no. 10: 8701. https://doi.org/10.3390/ijms24108701