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Journal of Nuclear Medicine

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A LONG-CIRCULATING AGENT FOR PSMA EXPRESSED PROSTATE CARCINOMA

Ming-Hsin Li, Shang-Nan Lo, Shih-Ming Wang, Su-Jung Chen, Shih-Ying Lee, Shih-Wei Lo, Ming-Wei Chen and Wei-Lin Lo
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 3097;
Ming-Hsin Li
1Isotope Application Division Institute of Nuclear Energy Research Taoyuan City Taiwan
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Shang-Nan Lo
1Isotope Application Division Institute of Nuclear Energy Research Taoyuan City Taiwan
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Shih-Ming Wang
1Isotope Application Division Institute of Nuclear Energy Research Taoyuan City Taiwan
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Su-Jung Chen
1Isotope Application Division Institute of Nuclear Energy Research Taoyuan City Taiwan
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Shih-Ying Lee
1Isotope Application Division Institute of Nuclear Energy Research Taoyuan City Taiwan
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Shih-Wei Lo
1Isotope Application Division Institute of Nuclear Energy Research Taoyuan City Taiwan
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Ming-Wei Chen
1Isotope Application Division Institute of Nuclear Energy Research Taoyuan City Taiwan
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Wei-Lin Lo
1Isotope Application Division Institute of Nuclear Energy Research Taoyuan City Taiwan
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Abstract

3097

Introduction: Prostate-specific membrane antigen (PSMA) is a well-known targeting for prostate cancer. PSMA-617 is prostate radionuclide ligand therapy (PRLT) classic idol of NAAG inhibitor-modified. We design a precursor MH-PC-AB-9 that has a spacer link urea-based NAAG inhibitor and albumin binder to change the pharmacokinetics of NAAG inhibitor for PSMA. We use lysine, tyrosine, tyrosine, and glutamic acid (from N-terminal to C-terminal) as a spacer. And 4-(p-Tolyl) butyric acid link the lysine's side chain as an albumin binder. The chelator is DOTA and the one carboxylic acid of DOTA is conjugating with lysine’ N-terminal.

Methods: 20 μg of the precursor was diluted with sodium acetate buffer pH6.0 and added to 0.1 GBq of [In-111] InCl3 in 0.01N HCl. The solution heated to 95 ℃ for 15 min with 500 rpm agitation. Radiochemical purity was established by thin layer chromatography (TLC) and high pressure liquid chromatography (HPLC). The TLC chamber was loaded with 10 % methanol in water. The Xselect HSS T3 column (4.6 mm x 250 mm) was used and eluted with a linear gradient from 20 to 60% acetonitrile in water (0.1% TFA) over 10 min at a flow rate of 0.8 mL/min. The detector was used gamma radiated detector and UV detector was adjusted for 220 nm. The bioactivity to recognized PSMA of [In-111] In-MH-PC-AB-9 was performed by LNCaP tumor-bearing mice.

Results: The chemical purity of [In-111] In-MH-PC-AB-9 was over 95% determined by TLC and HPLC. The retardation factor of free [In-111] In is 0.27 and [In-111] In-MH-PC-AB-9 is 0.95 in TLC. The retention time of free [In-111] In is 3.26 min and [In-111] In-MH-PC-AB-9 is 11.052 min in HPLC. The distribution of [In-111] In-MH-PC-AB-9 in tumor-bearing mice was imaging with nano-SPECT/CT at 1, 24, 72 hours. There still has radioactive accumulated until post-injection 72 hours at the tumor site.

Conclusions: The precursor MH-PC-AB-9 has long circulating time was provided by labeling with [In-111] InCl3 and injected into tumor-bearing mice. And the radioactive was increasing with post-injected time. Hence, MH-PC-AB-9 has improved the blood half-life of the NAAG inhibitor more than PSMA-617. Supporting data Figure1. Thin layer chromatography to analyze the radiochemical purity of [In-111] In-MH-PC-AB-9. A is free [In-111] InCl3; B is [In-111] In-MH-PC-AB-9. Figure2. The radiochemical purity of [In-111] In-MH-PC-AB-9 is analyzed by HPLC. The A and B is radio detector; C is UV detector. Figure3. The biodistribution of [In-111] In-MH-PC-AB-9 is imaging with nano-SPECT/CT at post-injected 1, 24 and 72 hours.

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Journal of Nuclear Medicine
Vol. 61, Issue supplement 1
May 1, 2020
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A LONG-CIRCULATING AGENT FOR PSMA EXPRESSED PROSTATE CARCINOMA
Ming-Hsin Li, Shang-Nan Lo, Shih-Ming Wang, Su-Jung Chen, Shih-Ying Lee, Shih-Wei Lo, Ming-Wei Chen, Wei-Lin Lo
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 3097;

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A LONG-CIRCULATING AGENT FOR PSMA EXPRESSED PROSTATE CARCINOMA
Ming-Hsin Li, Shang-Nan Lo, Shih-Ming Wang, Su-Jung Chen, Shih-Ying Lee, Shih-Wei Lo, Ming-Wei Chen, Wei-Lin Lo
Journal of Nuclear Medicine May 2020, 61 (supplement 1) 3097;
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