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Evaluation of Radiolabeling PSMA-Targeted Long Circulating Peptide as a Theranostic Agent in Human Prostate Tumor-Bearing Mice

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Future Trends and Challenges of Molecular Imaging and AI Innovation (FASMI 2020)

Abstract

The prostate-specific membrane antigen (PSMA) is a great target for prostate cancer in the current. The MH-PC-AB-56, a molecule with PSMA-targeted activity and with an albumin-binding motif, was radiolabeled with indium as a diagnostic agent and with lutetium with a therapeutic agent, respectively. We evaluated the molecule's theranostic application with 111In and 177Lu in NanoSPECT/CT imaging. Methods: The radiolabeled peptide, 111In/177Lu-MH-PC-AB-56, was performed with sodium acetate buffer and heating with 15 min or 30 min at 95℃. The radiochemical purity was analyzed by TLC and HPLC. The PSMA-expressed tumor cell LNCaP was implanted right front leg at BALB/c nude mice. NanoSPECT/CT image was performed at 1 h, 4 h, 24 h, 48 h, 72 h, and 96 h after injection of 111In-MH-PC-AB-56 or 177Lu-MH-PC-AB-56. Results: The radiochemical purity of 111In-MH-PC-AB-56 or 177Lu-MH-PC-AB-56 was 99.09 ± 0.38% and 98.87 ± 0.73% by radio-HPLC analysis, respectively. The in vitro labeling stability of both radiolabeled peptide was 97.0% ± 0.8% and 94.5% ± 2.5% at 4 h in normal saline by radio-HPLC analysis, respectively. The highest uptake of 111In-MH-PC-AB-56 in the tumor appeared at 24 h (43.78 ± 6.55%ID/g), and the uptake in the tumor was a decline after 24 h. During 1 h to 4 h, the kidney and muscle had the highest accumulation of 111In-MH-PC-AB-56 with 37.62 ± 3.69%ID/g to 39.66 ± 7.59%ID/g and 6.58 ± 0.59%ID/g to 6.70 ± 0.45%ID/g, respectively. The highest uptake of 177Lu-MH-PC-AB-56 in the tumor appeared at 24 h (22.08 ± 6.63%ID/g) and retained until 96 h (23.41 ± 5.18%ID/g). During 1 h to 4 h, the kidney had the highest accumulation of 177Lu-MH-PC-AB-56 with 40.35 ± 4.89%ID/g to 42.63 ± 20.14%ID/g. Conclusion: Our results indicated that both 111In-MH-PC-AB-56 and 177Lu-MH-PC-AB-56 highly accumulated at the tumor lesion, and both 111In-MH-PC-AB-56 and 177Lu-MH-PC-AB-56 were similar distribution in the liver and kidney with positive correlation (r = 0.960 and 0.979) by NanoSPECT/CT imaging.

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Acknowledgements

We thanked the support from the Ministry of Economic Affairs, ROC with grant number 108-EC-17-A-22-1587.

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The authors declare that they have no conflict of interest.

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Correspondence to Ming-Hsin Li .

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Li, MH. et al. (2022). Evaluation of Radiolabeling PSMA-Targeted Long Circulating Peptide as a Theranostic Agent in Human Prostate Tumor-Bearing Mice. In: Lin, KP., Liu, RS., Yang, BH. (eds) Future Trends and Challenges of Molecular Imaging and AI Innovation. FASMI 2020. Springer Proceedings in Physics, vol 272. Springer, Cham. https://doi.org/10.1007/978-3-030-92786-8_11

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