Synthesis, preclinical evaluation, and first-in-human study of Al18F-PSMA-Q for prostate cancer imaging
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature..
PURPOSE: To investigate the potential of a novel Al18F-labeled PSMA-targeted radiotracer for PCa diagnosis through both preclinical and pilot clinical studies.
METHODS: Al18F-PSMA-Q was prepared automatically. The binding affinity to PSMA was evaluated in vitro using the 22Rv1 (PSMA +) and PC-3 (PSMA -) cell lines. Pharmacokinetics evaluation, biodistribution study, Micro-PET imaging of Al18F-PSMA-Q in normal mice and tumor-bearing mice, and a comparison with 18F-DCFPyL were performed. PET/CT imaging was performed on 8 healthy volunteers and 20 newly diagnosed PCa patients at 1 h post-injection (p.i.). The biodistribution in human and preliminary diagnostic efficacy of Al18F-PSMA-Q were evaluated, and the radiation dosimetry was estimated using OLINDA/EXM 2.0 software.
RESULT: Qualified Al18F-PSMA-Q was efficiently prepared with a non-decay-corrected radiochemical yield (RCY) of 22.0-28.3%, a specific activity (SA) of > 50 GBq/μmol. The hydrophilicity was comparably high with a log P value of - 3.69 ± 0.39. Al18F-PSMA-Q was found to bind to PSMA specifically with a Ki value of 17.05 ± 1.14 nM. The distribution and elimination half-lives of Al18F-PSMA-Q were 3.93 min and 14.22 min, respectively, which were shorter than those of 18F-DCFPyL. Micro-PET imaging of Al18F-PSMA-Q can clearly differentiate 22Rv1 tumors from PC-3 tumors and background with a high SUVmax of 2.17 ± 0.42 and a tumor-to-muscle ratio of 84.37 ± 31.62, which were higher than those of 18F-DCFPyL (1.79 ± 0.39 and 13.25 ± 1.65). The uptake of Al18F-PSMA-Q in 22Rv1 cells and tumors can be substantially blocked by 2-PMPA. High level accumulation of Al18F-PSMA-Q was observed in organs physiologically expressing PSMA. Twenty-six tumor lesions were detected in 20 PCa patients, and the mean SUVmax values of primary tumors, lymph node metastasis, bone metastases, and tumor-muscle ratios were 19.71 ± 16.52, 5.11, 31.30 ± 29.85, and 44.77 ± 22.29, respectively. The mean SUVmax of tumors in patients with PSA > 10 ng/mL was significantly higher than that in patients with PSA ≤ 10 ng/mL (25.97 ± 18.64 vs. 10.33 ± 3.74). Meanwhile, the mean SUVmax of tumors in patients with a Gleason score ≥ 8 was significantly higher than that in patients with a Gleason score < 8 (31.85 ± 22.09 vs. 13.18 ± 11.58). The kidneys received the highest estimated dose of 0.098 ± 0.006 mGy/MBq, and the effective dose was calculated as 0.0128 ± 0.007 mGy/MBq.
CONCLUSION: The novel qualified PSMA-targeted radiotracer Al18F-PSMA-Q was conveniently prepared with favorable yield and SA. The results of preclinical and pilot clinical studies exhibited a high specific uptake in PCa lesions and an excellent tumor-to-background ratio with a reasonable radiation exposure, which indicated the great potential of Al18F-PSMA-Q for PCa imaging.
TRIAL REGISTRATION: Chinese Clinical trial registry ChiCTR2100053507, Registered 23 November 2021, retrospectively registered.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:49 |
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| Enthalten in: |
European journal of nuclear medicine and molecular imaging - 49(2022), 8 vom: 09. Juli, Seite 2774-2785 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Yitian [VerfasserIn] |
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| Links: |
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| Themen: |
Al18F |
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| Anmerkungen: |
Date Completed 21.06.2022 Date Revised 02.09.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00259-022-05775-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM339266082 |
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| 041 | |a eng | ||
| 100 | 1 | |a Wu, Yitian |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Synthesis, preclinical evaluation, and first-in-human study of Al18F-PSMA-Q for prostate cancer imaging |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Revised 02.09.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. | ||
| 520 | |a PURPOSE: To investigate the potential of a novel Al18F-labeled PSMA-targeted radiotracer for PCa diagnosis through both preclinical and pilot clinical studies | ||
| 520 | |a METHODS: Al18F-PSMA-Q was prepared automatically. The binding affinity to PSMA was evaluated in vitro using the 22Rv1 (PSMA +) and PC-3 (PSMA -) cell lines. Pharmacokinetics evaluation, biodistribution study, Micro-PET imaging of Al18F-PSMA-Q in normal mice and tumor-bearing mice, and a comparison with 18F-DCFPyL were performed. PET/CT imaging was performed on 8 healthy volunteers and 20 newly diagnosed PCa patients at 1 h post-injection (p.i.). The biodistribution in human and preliminary diagnostic efficacy of Al18F-PSMA-Q were evaluated, and the radiation dosimetry was estimated using OLINDA/EXM 2.0 software | ||
| 520 | |a RESULT: Qualified Al18F-PSMA-Q was efficiently prepared with a non-decay-corrected radiochemical yield (RCY) of 22.0-28.3%, a specific activity (SA) of > 50 GBq/μmol. The hydrophilicity was comparably high with a log P value of - 3.69 ± 0.39. Al18F-PSMA-Q was found to bind to PSMA specifically with a Ki value of 17.05 ± 1.14 nM. The distribution and elimination half-lives of Al18F-PSMA-Q were 3.93 min and 14.22 min, respectively, which were shorter than those of 18F-DCFPyL. Micro-PET imaging of Al18F-PSMA-Q can clearly differentiate 22Rv1 tumors from PC-3 tumors and background with a high SUVmax of 2.17 ± 0.42 and a tumor-to-muscle ratio of 84.37 ± 31.62, which were higher than those of 18F-DCFPyL (1.79 ± 0.39 and 13.25 ± 1.65). The uptake of Al18F-PSMA-Q in 22Rv1 cells and tumors can be substantially blocked by 2-PMPA. High level accumulation of Al18F-PSMA-Q was observed in organs physiologically expressing PSMA. Twenty-six tumor lesions were detected in 20 PCa patients, and the mean SUVmax values of primary tumors, lymph node metastasis, bone metastases, and tumor-muscle ratios were 19.71 ± 16.52, 5.11, 31.30 ± 29.85, and 44.77 ± 22.29, respectively. The mean SUVmax of tumors in patients with PSA > 10 ng/mL was significantly higher than that in patients with PSA ≤ 10 ng/mL (25.97 ± 18.64 vs. 10.33 ± 3.74). Meanwhile, the mean SUVmax of tumors in patients with a Gleason score ≥ 8 was significantly higher than that in patients with a Gleason score < 8 (31.85 ± 22.09 vs. 13.18 ± 11.58). The kidneys received the highest estimated dose of 0.098 ± 0.006 mGy/MBq, and the effective dose was calculated as 0.0128 ± 0.007 mGy/MBq | ||
| 520 | |a CONCLUSION: The novel qualified PSMA-targeted radiotracer Al18F-PSMA-Q was conveniently prepared with favorable yield and SA. The results of preclinical and pilot clinical studies exhibited a high specific uptake in PCa lesions and an excellent tumor-to-background ratio with a reasonable radiation exposure, which indicated the great potential of Al18F-PSMA-Q for PCa imaging | ||
| 520 | |a TRIAL REGISTRATION: Chinese Clinical trial registry ChiCTR2100053507, Registered 23 November 2021, retrospectively registered | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Al18F | |
| 650 | 4 | |a Clinical study | |
| 650 | 4 | |a PET | |
| 650 | 4 | |a PSMA | |
| 650 | 4 | |a Prostate cancer | |
| 650 | 7 | |a Radiopharmaceuticals |2 NLM | |
| 650 | 7 | |a Prostate-Specific Antigen |2 NLM | |
| 650 | 7 | |a EC 3.4.21.77 |2 NLM | |
| 700 | 1 | |a Zhang, Xiaojun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Haoxi |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Baixuan |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Jiahe |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Shuwei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jinming |e verfasserin |4 aut | |
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