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A comparison study of dynamic [18F]Alfatide II imaging and [11C]MET in orthotopic rat models of glioblastoma

Purpose To investigate and compare the dynamic positron emission tomography (PET) imaging with [ 18 F]Alfatide II Imaging and [ 11 C]Methionine ([ 11 C]MET) in orthotopic rat models of glioblastoma multiforme (GBM), and to assess the utility of [ 18 F]Alfatide II in detecting and evaluating neoangio...

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Published in:Journal of cancer research and clinical oncology 2024-04, Vol.150 (4), p.208-208, Article 208
Main Authors: Pan, Yue, Dang, Haodan, Zhou, Haoxi, Fu, Huaping, Wu, Shina, Liu, Huanhuan, Zhang, Jinming, Wang, Ruimin, Tian, Yuan, Xu, Baixuan
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container_title Journal of cancer research and clinical oncology
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creator Pan, Yue
Dang, Haodan
Zhou, Haoxi
Fu, Huaping
Wu, Shina
Liu, Huanhuan
Zhang, Jinming
Wang, Ruimin
Tian, Yuan
Xu, Baixuan
description Purpose To investigate and compare the dynamic positron emission tomography (PET) imaging with [ 18 F]Alfatide II Imaging and [ 11 C]Methionine ([ 11 C]MET) in orthotopic rat models of glioblastoma multiforme (GBM), and to assess the utility of [ 18 F]Alfatide II in detecting and evaluating neoangiogenesis in GBM. Methods [ 18 F]Alfatide II and [ 11 C]MET were injected into the orthotopic GBM rat models ( n  = 20, C6 glioma cells), followed by dynamic PET/MR scans 21 days after surgery of tumor implantation. On the PET image with both radiotracers, the MRI-based volume-of-interest (VOI) was manually delineated encompassing glioblastoma. Time-activity curves were expressed as tumor-to-normal brain ratio (TNR) parameters and PET pharmacokinetic modeling (PKM) performed using 2-tissue-compartment models (2TCM). Immunofluorescent staining (IFS), western blotting and blocking experiment of tumor tissue were performed for the validation. Results Compared to 11 C-MET, [ 18 F]Alfatide II presented a persistent accumulation in the tumor, albeit with a slightly lower SUVmean of 0.79 ± 0.25, and a reduced uptake in the contralateral normal brain tissue, respectively. This resulted in a markedly higher tumor-to-normal brain ratio (TNR) of 18.22 ± 1.91. The time–activity curve (TACs) showed a significant increase in radioactive uptake in tumor tissue, followed by a plateau phase up to 60 min for [ 18 F]Alfatide II (time to peak:255 s) and 40 min for [ 11 C]MET (time to peak:135 s) post injection. PKM confirmed significantly higher K 1 (0.23/0.07) and K 3 (0.26/0.09) in the tumor region compared to the normal brain with [ 18 F]Alfatide II. Compared to [ 11 C]MET imaging, PKM confirmed both significantly higher K 1 /K 2 (1.24 ± 0.79/1.05 ± 0.39) and K 3 /K 4 (11.93 ± 4.28/3.89 ± 1.29) in the tumor region with [ 18 F]Alfatide II. IFS confirmed significant expression of integrin and tumor vascularization in tumor region. Conclusion [ 18 F]Alfatide II demonstrates potential in imaging tumor-associated neovascularization in the context of glioblastoma multiforme (GBM), suggesting its utility as a tool for further exploration in neovascular characterization.
doi_str_mv 10.1007/s00432-024-05688-4
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Methods [ 18 F]Alfatide II and [ 11 C]MET were injected into the orthotopic GBM rat models ( n  = 20, C6 glioma cells), followed by dynamic PET/MR scans 21 days after surgery of tumor implantation. On the PET image with both radiotracers, the MRI-based volume-of-interest (VOI) was manually delineated encompassing glioblastoma. Time-activity curves were expressed as tumor-to-normal brain ratio (TNR) parameters and PET pharmacokinetic modeling (PKM) performed using 2-tissue-compartment models (2TCM). Immunofluorescent staining (IFS), western blotting and blocking experiment of tumor tissue were performed for the validation. Results Compared to 11 C-MET, [ 18 F]Alfatide II presented a persistent accumulation in the tumor, albeit with a slightly lower SUVmean of 0.79 ± 0.25, and a reduced uptake in the contralateral normal brain tissue, respectively. This resulted in a markedly higher tumor-to-normal brain ratio (TNR) of 18.22 ± 1.91. The time–activity curve (TACs) showed a significant increase in radioactive uptake in tumor tissue, followed by a plateau phase up to 60 min for [ 18 F]Alfatide II (time to peak:255 s) and 40 min for [ 11 C]MET (time to peak:135 s) post injection. PKM confirmed significantly higher K 1 (0.23/0.07) and K 3 (0.26/0.09) in the tumor region compared to the normal brain with [ 18 F]Alfatide II. Compared to [ 11 C]MET imaging, PKM confirmed both significantly higher K 1 /K 2 (1.24 ± 0.79/1.05 ± 0.39) and K 3 /K 4 (11.93 ± 4.28/3.89 ± 1.29) in the tumor region with [ 18 F]Alfatide II. IFS confirmed significant expression of integrin and tumor vascularization in tumor region. Conclusion [ 18 F]Alfatide II demonstrates potential in imaging tumor-associated neovascularization in the context of glioblastoma multiforme (GBM), suggesting its utility as a tool for further exploration in neovascular characterization.</description><identifier>ISSN: 1432-1335</identifier><identifier>ISSN: 0171-5216</identifier><identifier>EISSN: 1432-1335</identifier><identifier>DOI: 10.1007/s00432-024-05688-4</identifier><identifier>PMID: 38647690</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animal models ; Animals ; Brain Neoplasms - diagnostic imaging ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; Brain tumors ; Cancer Research ; Carbon Radioisotopes ; Cell Line, Tumor ; Disease Models, Animal ; Fluorine Radioisotopes ; Glioblastoma ; Glioblastoma - diagnostic imaging ; Glioblastoma - metabolism ; Glioblastoma - pathology ; Glioma ; Glioma cells ; Hematology ; Humans ; Internal Medicine ; Male ; Medicine ; Medicine &amp; Public Health ; Methionine ; Methionine - pharmacokinetics ; Neuroimaging ; Oncology ; Peptides, Cyclic - pharmacokinetics ; Pharmacokinetics ; Positron emission tomography ; Positron-Emission Tomography - methods ; Radiopharmaceuticals - pharmacokinetics ; Rats ; Vascularization ; Western blotting</subject><ispartof>Journal of cancer research and clinical oncology, 2024-04, Vol.150 (4), p.208-208, Article 208</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c426t-4b8201d3c3b19f569dbe30572301e1db398c5763add55f6f7d7eda2ecdb6e2803</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38647690$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pan, Yue</creatorcontrib><creatorcontrib>Dang, Haodan</creatorcontrib><creatorcontrib>Zhou, Haoxi</creatorcontrib><creatorcontrib>Fu, Huaping</creatorcontrib><creatorcontrib>Wu, Shina</creatorcontrib><creatorcontrib>Liu, Huanhuan</creatorcontrib><creatorcontrib>Zhang, Jinming</creatorcontrib><creatorcontrib>Wang, Ruimin</creatorcontrib><creatorcontrib>Tian, Yuan</creatorcontrib><creatorcontrib>Xu, Baixuan</creatorcontrib><title>A comparison study of dynamic [18F]Alfatide II imaging and [11C]MET in orthotopic rat models of glioblastoma</title><title>Journal of cancer research and clinical oncology</title><addtitle>J Cancer Res Clin Oncol</addtitle><addtitle>J Cancer Res Clin Oncol</addtitle><description>Purpose To investigate and compare the dynamic positron emission tomography (PET) imaging with [ 18 F]Alfatide II Imaging and [ 11 C]Methionine ([ 11 C]MET) in orthotopic rat models of glioblastoma multiforme (GBM), and to assess the utility of [ 18 F]Alfatide II in detecting and evaluating neoangiogenesis in GBM. Methods [ 18 F]Alfatide II and [ 11 C]MET were injected into the orthotopic GBM rat models ( n  = 20, C6 glioma cells), followed by dynamic PET/MR scans 21 days after surgery of tumor implantation. On the PET image with both radiotracers, the MRI-based volume-of-interest (VOI) was manually delineated encompassing glioblastoma. Time-activity curves were expressed as tumor-to-normal brain ratio (TNR) parameters and PET pharmacokinetic modeling (PKM) performed using 2-tissue-compartment models (2TCM). Immunofluorescent staining (IFS), western blotting and blocking experiment of tumor tissue were performed for the validation. Results Compared to 11 C-MET, [ 18 F]Alfatide II presented a persistent accumulation in the tumor, albeit with a slightly lower SUVmean of 0.79 ± 0.25, and a reduced uptake in the contralateral normal brain tissue, respectively. This resulted in a markedly higher tumor-to-normal brain ratio (TNR) of 18.22 ± 1.91. The time–activity curve (TACs) showed a significant increase in radioactive uptake in tumor tissue, followed by a plateau phase up to 60 min for [ 18 F]Alfatide II (time to peak:255 s) and 40 min for [ 11 C]MET (time to peak:135 s) post injection. PKM confirmed significantly higher K 1 (0.23/0.07) and K 3 (0.26/0.09) in the tumor region compared to the normal brain with [ 18 F]Alfatide II. Compared to [ 11 C]MET imaging, PKM confirmed both significantly higher K 1 /K 2 (1.24 ± 0.79/1.05 ± 0.39) and K 3 /K 4 (11.93 ± 4.28/3.89 ± 1.29) in the tumor region with [ 18 F]Alfatide II. IFS confirmed significant expression of integrin and tumor vascularization in tumor region. 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Public Health</subject><subject>Methionine</subject><subject>Methionine - pharmacokinetics</subject><subject>Neuroimaging</subject><subject>Oncology</subject><subject>Peptides, Cyclic - pharmacokinetics</subject><subject>Pharmacokinetics</subject><subject>Positron emission tomography</subject><subject>Positron-Emission Tomography - methods</subject><subject>Radiopharmaceuticals - pharmacokinetics</subject><subject>Rats</subject><subject>Vascularization</subject><subject>Western blotting</subject><issn>1432-1335</issn><issn>0171-5216</issn><issn>1432-1335</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kcFvFCEUxonR2Hb1H_BgSLx4GX0MAzN7MptNazep8VJPpiEMMFMaBlZgmux_L-PWWj14gvB-7-N770PoDYEPBKD9mAAaWldQNxUw3nVV8wydkuWJUMqeP7mfoLOU7gBIy9r6JTqhHW9avoZT5DZYhWkvo03B45RnfcBhwPrg5WQV_k66i5uNG2S22uDdDttJjtaPWHpdimR78-X8GluPQ8y3IYd96Yky4ylo49KiNDobeidTDpN8hV4M0iXz-uFcoW8X59fby-rq6-fddnNVqabmuWr6rgaiqaI9WQ-Mr3VvKBTnFIghuqfrTrGWU6k1YwMfWt0aLWujdM9N3QFdoU9H3f3cT0Yr43OUTuxjcR8PIkgr_q54eyvGcC8IAcqasrYVev-gEMOP2aQsJpuUcU56E-YkKDSMLJvlBX33D3oX5ujLfAtFWfHNu0LVR0rFkFI0w6MbAmJJUxzTFCVN8StNsbh4-3SOx5bf8RWAHoFUSn408c_f_5H9CR_5qow</recordid><startdate>20240422</startdate><enddate>20240422</enddate><creator>Pan, Yue</creator><creator>Dang, Haodan</creator><creator>Zhou, Haoxi</creator><creator>Fu, Huaping</creator><creator>Wu, Shina</creator><creator>Liu, Huanhuan</creator><creator>Zhang, Jinming</creator><creator>Wang, Ruimin</creator><creator>Tian, Yuan</creator><creator>Xu, Baixuan</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20240422</creationdate><title>A comparison study of dynamic [18F]Alfatide II imaging and [11C]MET in orthotopic rat models of glioblastoma</title><author>Pan, Yue ; 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Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cancer research and clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pan, Yue</au><au>Dang, Haodan</au><au>Zhou, Haoxi</au><au>Fu, Huaping</au><au>Wu, Shina</au><au>Liu, Huanhuan</au><au>Zhang, Jinming</au><au>Wang, Ruimin</au><au>Tian, Yuan</au><au>Xu, Baixuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A comparison study of dynamic [18F]Alfatide II imaging and [11C]MET in orthotopic rat models of glioblastoma</atitle><jtitle>Journal of cancer research and clinical oncology</jtitle><stitle>J Cancer Res Clin Oncol</stitle><addtitle>J Cancer Res Clin Oncol</addtitle><date>2024-04-22</date><risdate>2024</risdate><volume>150</volume><issue>4</issue><spage>208</spage><epage>208</epage><pages>208-208</pages><artnum>208</artnum><issn>1432-1335</issn><issn>0171-5216</issn><eissn>1432-1335</eissn><abstract>Purpose To investigate and compare the dynamic positron emission tomography (PET) imaging with [ 18 F]Alfatide II Imaging and [ 11 C]Methionine ([ 11 C]MET) in orthotopic rat models of glioblastoma multiforme (GBM), and to assess the utility of [ 18 F]Alfatide II in detecting and evaluating neoangiogenesis in GBM. Methods [ 18 F]Alfatide II and [ 11 C]MET were injected into the orthotopic GBM rat models ( n  = 20, C6 glioma cells), followed by dynamic PET/MR scans 21 days after surgery of tumor implantation. On the PET image with both radiotracers, the MRI-based volume-of-interest (VOI) was manually delineated encompassing glioblastoma. Time-activity curves were expressed as tumor-to-normal brain ratio (TNR) parameters and PET pharmacokinetic modeling (PKM) performed using 2-tissue-compartment models (2TCM). Immunofluorescent staining (IFS), western blotting and blocking experiment of tumor tissue were performed for the validation. Results Compared to 11 C-MET, [ 18 F]Alfatide II presented a persistent accumulation in the tumor, albeit with a slightly lower SUVmean of 0.79 ± 0.25, and a reduced uptake in the contralateral normal brain tissue, respectively. This resulted in a markedly higher tumor-to-normal brain ratio (TNR) of 18.22 ± 1.91. The time–activity curve (TACs) showed a significant increase in radioactive uptake in tumor tissue, followed by a plateau phase up to 60 min for [ 18 F]Alfatide II (time to peak:255 s) and 40 min for [ 11 C]MET (time to peak:135 s) post injection. PKM confirmed significantly higher K 1 (0.23/0.07) and K 3 (0.26/0.09) in the tumor region compared to the normal brain with [ 18 F]Alfatide II. Compared to [ 11 C]MET imaging, PKM confirmed both significantly higher K 1 /K 2 (1.24 ± 0.79/1.05 ± 0.39) and K 3 /K 4 (11.93 ± 4.28/3.89 ± 1.29) in the tumor region with [ 18 F]Alfatide II. IFS confirmed significant expression of integrin and tumor vascularization in tumor region. Conclusion [ 18 F]Alfatide II demonstrates potential in imaging tumor-associated neovascularization in the context of glioblastoma multiforme (GBM), suggesting its utility as a tool for further exploration in neovascular characterization.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>38647690</pmid><doi>10.1007/s00432-024-05688-4</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Animal models
Animals
Brain Neoplasms - diagnostic imaging
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Brain tumors
Cancer Research
Carbon Radioisotopes
Cell Line, Tumor
Disease Models, Animal
Fluorine Radioisotopes
Glioblastoma
Glioblastoma - diagnostic imaging
Glioblastoma - metabolism
Glioblastoma - pathology
Glioma
Glioma cells
Hematology
Humans
Internal Medicine
Male
Medicine
Medicine & Public Health
Methionine
Methionine - pharmacokinetics
Neuroimaging
Oncology
Peptides, Cyclic - pharmacokinetics
Pharmacokinetics
Positron emission tomography
Positron-Emission Tomography - methods
Radiopharmaceuticals - pharmacokinetics
Rats
Vascularization
Western blotting
title A comparison study of dynamic [18F]Alfatide II imaging and [11C]MET in orthotopic rat models of glioblastoma
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