Synthesis, preclinical evaluation, and first-in-human study of Al18F-PSMA-Q for prostate cancer imaging
Purpose To investigate the potential of a novel Al 18 F-labeled PSMA-targeted radiotracer for PCa diagnosis through both preclinical and pilot clinical studies. Methods Al 18 F-PSMA-Q was prepared automatically. The binding affinity to PSMA was evaluated in vitro using the 22Rv1 (PSMA +) and PC-3 (P...
Gespeichert in:
| Veröffentlicht in: | European journal of nuclear medicine and molecular imaging 2022-07, Vol.49 (8), p.2774-2785 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2785 |
|---|---|
| container_issue | 8 |
| container_start_page | 2774 |
| container_title | European journal of nuclear medicine and molecular imaging |
| container_volume | 49 |
| creator | Wu, Yitian Zhang, Xiaojun Zhou, Haoxi Xu, Baixuan Tian, Jiahe Sun, Shuwei Zhang, Jinming |
| description | Purpose
To investigate the potential of a novel Al
18
F-labeled PSMA-targeted radiotracer for PCa diagnosis through both preclinical and pilot clinical studies.
Methods
Al
18
F-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 Al
18
F-PSMA-Q in normal mice and tumor-bearing mice, and a comparison with
18
F-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 Al
18
F-PSMA-Q were evaluated, and the radiation dosimetry was estimated using OLINDA/EXM 2.0 software.
Result
Qualified Al
18
F-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. Al
18
F-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 Al
18
F-PSMA-Q were 3.93 min and 14.22 min, respectively, which were shorter than those of
18
F-DCFPyL. Micro-PET imaging of Al
18
F-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
18
F-DCFPyL (1.79 ± 0.39 and 13.25 ± 1.65). The uptake of Al
18
F-PSMA-Q in 22Rv1 cells and tumors can be substantially blocked by 2-PMPA. High level accumulation of Al
18
F-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 |
| doi_str_mv | 10.1007/s00259-022-05775-z |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2648900963</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2678132159</sourcerecordid><originalsourceid>FETCH-LOGICAL-c197z-a1474b05bfac56043b0fcdab9c733e07a44ac313e6c012c71ba55c240662d0143</originalsourceid><addsrcrecordid>eNp9kMFLwzAYxYsoOKf_gKeAFw-LfknapjmO4VSYqEzPIc3SLaNLZ9IK219vtKLgwdP3HX7v8d5LknMCVwSAXwcAmgkMlGLIOM_w_iAZkJwIzKEQhz8_h-PkJIQ1ACloIQbJcr5z7coEG0Zo642urbNa1ci8q7pTrW3cCCm3QJX1ocXW4VW3UQ6FtlvsUFOhcU2KKX6aP4zxM6oaH02a0KrWIK2cNh7ZjVpatzxNjipVB3P2fYfJ6_TmZXKHZ4-395PxDGsi-B4rkvK0hKyslM5ySFkJlV6oUmjOmAGu0lRpRpjJNRCqOSlVlmmaQp7TBZCUDZPL3jfmeOtMaOXGBm3qWjnTdEHSPC0EgMhZRC_-oOum8y6mixQvCKMkE5GiPaVjseBNJbc-dvI7SUB-bi_77WXcXn5tL_dRxHpRiLBbGv9r_Y_qA71ghrE</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2678132159</pqid></control><display><type>article</type><title>Synthesis, preclinical evaluation, and first-in-human study of Al18F-PSMA-Q for prostate cancer imaging</title><source>SpringerLink Journals - AutoHoldings</source><creator>Wu, Yitian ; Zhang, Xiaojun ; Zhou, Haoxi ; Xu, Baixuan ; Tian, Jiahe ; Sun, Shuwei ; Zhang, Jinming</creator><creatorcontrib>Wu, Yitian ; Zhang, Xiaojun ; Zhou, Haoxi ; Xu, Baixuan ; Tian, Jiahe ; Sun, Shuwei ; Zhang, Jinming</creatorcontrib><description>Purpose
To investigate the potential of a novel Al
18
F-labeled PSMA-targeted radiotracer for PCa diagnosis through both preclinical and pilot clinical studies.
Methods
Al
18
F-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 Al
18
F-PSMA-Q in normal mice and tumor-bearing mice, and a comparison with
18
F-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 Al
18
F-PSMA-Q were evaluated, and the radiation dosimetry was estimated using OLINDA/EXM 2.0 software.
Result
Qualified Al
18
F-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. Al
18
F-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 Al
18
F-PSMA-Q were 3.93 min and 14.22 min, respectively, which were shorter than those of
18
F-DCFPyL. Micro-PET imaging of Al
18
F-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
18
F-DCFPyL (1.79 ± 0.39 and 13.25 ± 1.65). The uptake of Al
18
F-PSMA-Q in 22Rv1 cells and tumors can be substantially blocked by 2-PMPA. High level accumulation of Al
18
F-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 Al
18
F-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 Al
18
F-PSMA-Q for PCa imaging.
Trial registration
Chinese Clinical trial registry ChiCTR2100053507, Registered 23 November 2021, retrospectively registered.</description><identifier>ISSN: 1619-7070</identifier><identifier>EISSN: 1619-7089</identifier><identifier>DOI: 10.1007/s00259-022-05775-z</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Biodistribution ; Bone tumors ; Cardiology ; Computed tomography ; Dosimeters ; Dosimetry ; Fluorine isotopes ; Imaging ; Kidneys ; Lesions ; Lymph nodes ; Medical imaging ; Medicine ; Medicine & Public Health ; Metastases ; Muscles ; Nuclear Medicine ; Oncology ; Oncology – Genitourinary ; Organs ; Original Article ; Orthopedics ; Patients ; Pharmacokinetics ; Positron emission ; Prostate cancer ; Radiation ; Radiation effects ; Radioactive tracers ; Radiochemistry ; Radiology ; Tomography ; Tumors</subject><ispartof>European journal of nuclear medicine and molecular imaging, 2022-07, Vol.49 (8), p.2774-2785</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c197z-a1474b05bfac56043b0fcdab9c733e07a44ac313e6c012c71ba55c240662d0143</citedby><cites>FETCH-LOGICAL-c197z-a1474b05bfac56043b0fcdab9c733e07a44ac313e6c012c71ba55c240662d0143</cites><orcidid>0000-0002-9425-5180</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00259-022-05775-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00259-022-05775-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,41493,42562,51324</link.rule.ids></links><search><creatorcontrib>Wu, Yitian</creatorcontrib><creatorcontrib>Zhang, Xiaojun</creatorcontrib><creatorcontrib>Zhou, Haoxi</creatorcontrib><creatorcontrib>Xu, Baixuan</creatorcontrib><creatorcontrib>Tian, Jiahe</creatorcontrib><creatorcontrib>Sun, Shuwei</creatorcontrib><creatorcontrib>Zhang, Jinming</creatorcontrib><title>Synthesis, preclinical evaluation, and first-in-human study of Al18F-PSMA-Q for prostate cancer imaging</title><title>European journal of nuclear medicine and molecular imaging</title><addtitle>Eur J Nucl Med Mol Imaging</addtitle><description>Purpose
To investigate the potential of a novel Al
18
F-labeled PSMA-targeted radiotracer for PCa diagnosis through both preclinical and pilot clinical studies.
Methods
Al
18
F-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 Al
18
F-PSMA-Q in normal mice and tumor-bearing mice, and a comparison with
18
F-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 Al
18
F-PSMA-Q were evaluated, and the radiation dosimetry was estimated using OLINDA/EXM 2.0 software.
Result
Qualified Al
18
F-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. Al
18
F-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 Al
18
F-PSMA-Q were 3.93 min and 14.22 min, respectively, which were shorter than those of
18
F-DCFPyL. Micro-PET imaging of Al
18
F-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
18
F-DCFPyL (1.79 ± 0.39 and 13.25 ± 1.65). The uptake of Al
18
F-PSMA-Q in 22Rv1 cells and tumors can be substantially blocked by 2-PMPA. High level accumulation of Al
18
F-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 Al
18
F-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 Al
18
F-PSMA-Q for PCa imaging.
Trial registration
Chinese Clinical trial registry ChiCTR2100053507, Registered 23 November 2021, retrospectively registered.</description><subject>Biodistribution</subject><subject>Bone tumors</subject><subject>Cardiology</subject><subject>Computed tomography</subject><subject>Dosimeters</subject><subject>Dosimetry</subject><subject>Fluorine isotopes</subject><subject>Imaging</subject><subject>Kidneys</subject><subject>Lesions</subject><subject>Lymph nodes</subject><subject>Medical imaging</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Muscles</subject><subject>Nuclear Medicine</subject><subject>Oncology</subject><subject>Oncology – Genitourinary</subject><subject>Organs</subject><subject>Original Article</subject><subject>Orthopedics</subject><subject>Patients</subject><subject>Pharmacokinetics</subject><subject>Positron emission</subject><subject>Prostate cancer</subject><subject>Radiation</subject><subject>Radiation effects</subject><subject>Radioactive tracers</subject><subject>Radiochemistry</subject><subject>Radiology</subject><subject>Tomography</subject><subject>Tumors</subject><issn>1619-7070</issn><issn>1619-7089</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kMFLwzAYxYsoOKf_gKeAFw-LfknapjmO4VSYqEzPIc3SLaNLZ9IK219vtKLgwdP3HX7v8d5LknMCVwSAXwcAmgkMlGLIOM_w_iAZkJwIzKEQhz8_h-PkJIQ1ACloIQbJcr5z7coEG0Zo642urbNa1ci8q7pTrW3cCCm3QJX1ocXW4VW3UQ6FtlvsUFOhcU2KKX6aP4zxM6oaH02a0KrWIK2cNh7ZjVpatzxNjipVB3P2fYfJ6_TmZXKHZ4-395PxDGsi-B4rkvK0hKyslM5ySFkJlV6oUmjOmAGu0lRpRpjJNRCqOSlVlmmaQp7TBZCUDZPL3jfmeOtMaOXGBm3qWjnTdEHSPC0EgMhZRC_-oOum8y6mixQvCKMkE5GiPaVjseBNJbc-dvI7SUB-bi_77WXcXn5tL_dRxHpRiLBbGv9r_Y_qA71ghrE</recordid><startdate>20220701</startdate><enddate>20220701</enddate><creator>Wu, Yitian</creator><creator>Zhang, Xiaojun</creator><creator>Zhou, Haoxi</creator><creator>Xu, Baixuan</creator><creator>Tian, Jiahe</creator><creator>Sun, Shuwei</creator><creator>Zhang, Jinming</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9425-5180</orcidid></search><sort><creationdate>20220701</creationdate><title>Synthesis, preclinical evaluation, and first-in-human study of Al18F-PSMA-Q for prostate cancer imaging</title><author>Wu, Yitian ; Zhang, Xiaojun ; Zhou, Haoxi ; Xu, Baixuan ; Tian, Jiahe ; Sun, Shuwei ; Zhang, Jinming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c197z-a1474b05bfac56043b0fcdab9c733e07a44ac313e6c012c71ba55c240662d0143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Biodistribution</topic><topic>Bone tumors</topic><topic>Cardiology</topic><topic>Computed tomography</topic><topic>Dosimeters</topic><topic>Dosimetry</topic><topic>Fluorine isotopes</topic><topic>Imaging</topic><topic>Kidneys</topic><topic>Lesions</topic><topic>Lymph nodes</topic><topic>Medical imaging</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Muscles</topic><topic>Nuclear Medicine</topic><topic>Oncology</topic><topic>Oncology – Genitourinary</topic><topic>Organs</topic><topic>Original Article</topic><topic>Orthopedics</topic><topic>Patients</topic><topic>Pharmacokinetics</topic><topic>Positron emission</topic><topic>Prostate cancer</topic><topic>Radiation</topic><topic>Radiation effects</topic><topic>Radioactive tracers</topic><topic>Radiochemistry</topic><topic>Radiology</topic><topic>Tomography</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Yitian</creatorcontrib><creatorcontrib>Zhang, Xiaojun</creatorcontrib><creatorcontrib>Zhou, Haoxi</creatorcontrib><creatorcontrib>Xu, Baixuan</creatorcontrib><creatorcontrib>Tian, Jiahe</creatorcontrib><creatorcontrib>Sun, Shuwei</creatorcontrib><creatorcontrib>Zhang, Jinming</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>Proquest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of nuclear medicine and molecular imaging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Yitian</au><au>Zhang, Xiaojun</au><au>Zhou, Haoxi</au><au>Xu, Baixuan</au><au>Tian, Jiahe</au><au>Sun, Shuwei</au><au>Zhang, Jinming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis, preclinical evaluation, and first-in-human study of Al18F-PSMA-Q for prostate cancer imaging</atitle><jtitle>European journal of nuclear medicine and molecular imaging</jtitle><stitle>Eur J Nucl Med Mol Imaging</stitle><date>2022-07-01</date><risdate>2022</risdate><volume>49</volume><issue>8</issue><spage>2774</spage><epage>2785</epage><pages>2774-2785</pages><issn>1619-7070</issn><eissn>1619-7089</eissn><abstract>Purpose
To investigate the potential of a novel Al
18
F-labeled PSMA-targeted radiotracer for PCa diagnosis through both preclinical and pilot clinical studies.
Methods
Al
18
F-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 Al
18
F-PSMA-Q in normal mice and tumor-bearing mice, and a comparison with
18
F-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 Al
18
F-PSMA-Q were evaluated, and the radiation dosimetry was estimated using OLINDA/EXM 2.0 software.
Result
Qualified Al
18
F-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. Al
18
F-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 Al
18
F-PSMA-Q were 3.93 min and 14.22 min, respectively, which were shorter than those of
18
F-DCFPyL. Micro-PET imaging of Al
18
F-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
18
F-DCFPyL (1.79 ± 0.39 and 13.25 ± 1.65). The uptake of Al
18
F-PSMA-Q in 22Rv1 cells and tumors can be substantially blocked by 2-PMPA. High level accumulation of Al
18
F-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 Al
18
F-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 Al
18
F-PSMA-Q for PCa imaging.
Trial registration
Chinese Clinical trial registry ChiCTR2100053507, Registered 23 November 2021, retrospectively registered.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><doi>10.1007/s00259-022-05775-z</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-9425-5180</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1619-7070 |
| ispartof | European journal of nuclear medicine and molecular imaging, 2022-07, Vol.49 (8), p.2774-2785 |
| issn | 1619-7070 1619-7089 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2648900963 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | Biodistribution Bone tumors Cardiology Computed tomography Dosimeters Dosimetry Fluorine isotopes Imaging Kidneys Lesions Lymph nodes Medical imaging Medicine Medicine & Public Health Metastases Muscles Nuclear Medicine Oncology Oncology – Genitourinary Organs Original Article Orthopedics Patients Pharmacokinetics Positron emission Prostate cancer Radiation Radiation effects Radioactive tracers Radiochemistry Radiology Tomography Tumors |
| title | Synthesis, preclinical evaluation, and first-in-human study of Al18F-PSMA-Q for prostate cancer imaging |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-12T03%3A43%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Synthesis,%20preclinical%20evaluation,%20and%20first-in-human%20study%20of%20Al18F-PSMA-Q%20for%20prostate%20cancer%20imaging&rft.jtitle=European%20journal%20of%20nuclear%20medicine%20and%20molecular%20imaging&rft.au=Wu,%20Yitian&rft.date=2022-07-01&rft.volume=49&rft.issue=8&rft.spage=2774&rft.epage=2785&rft.pages=2774-2785&rft.issn=1619-7070&rft.eissn=1619-7089&rft_id=info:doi/10.1007/s00259-022-05775-z&rft_dat=%3Cproquest_cross%3E2678132159%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2678132159&rft_id=info:pmid/&rfr_iscdi=true |