[18F]KS1, a novel ascorbate-based ligand images ROS in tumor models of rodents and nonhuman primates
Over production of reactive oxygen species (ROS) caused by altered redox regulation of signaling pathways is common in many types of cancers. While PET imaging is recognized as the standard tool for cancer imaging, there are no clinically-approved PET radiotracers for ROS-imaging in cancer diagnosis...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222013269 |
| _version_ | 1811180246687285248 |
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| author | Naresh Damuka Nagaraju Bashetti Akiva Mintz Avinash H. Bansode Mack Miller Ivan Krizan Cristina Furdui Bhuvanachandra Bhoopal Krishna Kumar Gollapelli JV Shanmukha Kumar Gagan Deep Greg Dugan Mark Cline Kiran Kumar Solingapuram Sai |
| author_facet | Naresh Damuka Nagaraju Bashetti Akiva Mintz Avinash H. Bansode Mack Miller Ivan Krizan Cristina Furdui Bhuvanachandra Bhoopal Krishna Kumar Gollapelli JV Shanmukha Kumar Gagan Deep Greg Dugan Mark Cline Kiran Kumar Solingapuram Sai |
| author_sort | Naresh Damuka |
| collection | DOAJ |
| description | Over production of reactive oxygen species (ROS) caused by altered redox regulation of signaling pathways is common in many types of cancers. While PET imaging is recognized as the standard tool for cancer imaging, there are no clinically-approved PET radiotracers for ROS-imaging in cancer diagnosis and treatment. An ascorbate-based radio ligand promises to meet this urgent need. Our laboratory recently synthesized [18F] KS1, a fluoroethoxy furanose ring-containing ascorbate derivative, to track ROS in prostate tumor-bearing mice. Here we report cell uptake assays of [18F]KS1 with different ROS-regulating agents, PET imaging in head and neck squamous cell carcinoma (HNSCC) mice, and doxorubicin-induced rats; PET imaging in healthy and irradiated hepatic tumor-bearing rhesus to demonstrate its translational potential. Our preliminary evaluations demonstrated that KS1 do not generate ROS in tumor cells at tracer-level concentrations and tumor-killing properties at pharmacologic doses. [18F]KS1 uptake was low in HNSCC pretreated with ROS blockers, and high with ROS inducers. Tumors in high ROS-expressing SCC-61 took up significantly more [18F]KS1 than rSCC-61 (low-ROS expressing HNSCC); high uptake in doxorubicin-treated rats compared to saline-treated controls. Rodent biodistribution and PET imaging of [18F]KS1 in healthy rhesus monkeys demonstrated its favorable safety, pharmacokinetic properties with excellent washout profile, within 3.0 h of radiotracer administration. High uptake of [18F]KS1 in liver tumor tissues of the irradiated hepatic tumor-bearing monkey showed target selectivity. Our strong data in vitro, in vivo, and ex vivo here supports the high translational utility of [18F]KS1 to image ROS. |
| first_indexed | 2024-04-11T06:47:16Z |
| format | Article |
| id | doaj.art-9037725abf044ab3a4b3c63fe778673b |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-11T06:47:16Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-9037725abf044ab3a4b3c63fe778673b2022-12-22T04:39:19ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-12-01156113937[18F]KS1, a novel ascorbate-based ligand images ROS in tumor models of rodents and nonhuman primatesNaresh Damuka0Nagaraju Bashetti1Akiva Mintz2Avinash H. Bansode3Mack Miller4Ivan Krizan5Cristina Furdui6Bhuvanachandra Bhoopal7Krishna Kumar Gollapelli8JV Shanmukha Kumar9Gagan Deep10Greg Dugan11Mark Cline12Kiran Kumar Solingapuram Sai13Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Chemistry, Koneru Lakshmaiah Education Foundation, Andhra Pradesh, IndiaDepartment of Radiology, Columbia University, New York, NY, United StatesDepartment of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Chemistry, Koneru Lakshmaiah Education Foundation, Andhra Pradesh, IndiaDepartment of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United StatesDepartment of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, United States; Correspondence to: Department of Radiology. Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.Over production of reactive oxygen species (ROS) caused by altered redox regulation of signaling pathways is common in many types of cancers. While PET imaging is recognized as the standard tool for cancer imaging, there are no clinically-approved PET radiotracers for ROS-imaging in cancer diagnosis and treatment. An ascorbate-based radio ligand promises to meet this urgent need. Our laboratory recently synthesized [18F] KS1, a fluoroethoxy furanose ring-containing ascorbate derivative, to track ROS in prostate tumor-bearing mice. Here we report cell uptake assays of [18F]KS1 with different ROS-regulating agents, PET imaging in head and neck squamous cell carcinoma (HNSCC) mice, and doxorubicin-induced rats; PET imaging in healthy and irradiated hepatic tumor-bearing rhesus to demonstrate its translational potential. Our preliminary evaluations demonstrated that KS1 do not generate ROS in tumor cells at tracer-level concentrations and tumor-killing properties at pharmacologic doses. [18F]KS1 uptake was low in HNSCC pretreated with ROS blockers, and high with ROS inducers. Tumors in high ROS-expressing SCC-61 took up significantly more [18F]KS1 than rSCC-61 (low-ROS expressing HNSCC); high uptake in doxorubicin-treated rats compared to saline-treated controls. Rodent biodistribution and PET imaging of [18F]KS1 in healthy rhesus monkeys demonstrated its favorable safety, pharmacokinetic properties with excellent washout profile, within 3.0 h of radiotracer administration. High uptake of [18F]KS1 in liver tumor tissues of the irradiated hepatic tumor-bearing monkey showed target selectivity. Our strong data in vitro, in vivo, and ex vivo here supports the high translational utility of [18F]KS1 to image ROS.http://www.sciencedirect.com/science/article/pii/S0753332222013269Positron emission tomography imagingReactive oxygen speciesAscorbateBiodistribution, RadioligandsCancer |
| spellingShingle | Naresh Damuka Nagaraju Bashetti Akiva Mintz Avinash H. Bansode Mack Miller Ivan Krizan Cristina Furdui Bhuvanachandra Bhoopal Krishna Kumar Gollapelli JV Shanmukha Kumar Gagan Deep Greg Dugan Mark Cline Kiran Kumar Solingapuram Sai [18F]KS1, a novel ascorbate-based ligand images ROS in tumor models of rodents and nonhuman primates Biomedicine & Pharmacotherapy Positron emission tomography imaging Reactive oxygen species Ascorbate Biodistribution, Radioligands Cancer |
| title | [18F]KS1, a novel ascorbate-based ligand images ROS in tumor models of rodents and nonhuman primates |
| title_full | [18F]KS1, a novel ascorbate-based ligand images ROS in tumor models of rodents and nonhuman primates |
| title_fullStr | [18F]KS1, a novel ascorbate-based ligand images ROS in tumor models of rodents and nonhuman primates |
| title_full_unstemmed | [18F]KS1, a novel ascorbate-based ligand images ROS in tumor models of rodents and nonhuman primates |
| title_short | [18F]KS1, a novel ascorbate-based ligand images ROS in tumor models of rodents and nonhuman primates |
| title_sort | 18f ks1 a novel ascorbate based ligand images ros in tumor models of rodents and nonhuman primates |
| topic | Positron emission tomography imaging Reactive oxygen species Ascorbate Biodistribution, Radioligands Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222013269 |
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