Novel positron emission tomography imaging targeting cell surface glycans for pancreatic cancer: 18 F ‐labeled rBC2LCN lectin
Advancement in early detection modalities will greatly improve the overall prognoses of pancreatic ductal adenocarcinoma (PDAC). For this purpose, we report a novel class of tumor‐specific probes for positron emission tomography (PET) based on targeting cell surface glycans. The PDAC‐targeting abili...
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| Vydané v: | Cancer science Ročník 114; číslo 8; s. 3364 - 3373 |
|---|---|
| Hlavní autori: | , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
England
01.08.2023
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| ISSN: | 1347-9032, 1349-7006, 1349-7006 |
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| Abstract | Advancement in early detection modalities will greatly improve the overall prognoses of pancreatic ductal adenocarcinoma (PDAC). For this purpose, we report a novel class of tumor‐specific probes for positron emission tomography (PET) based on targeting cell surface glycans. The PDAC‐targeting ability of rBC2LCN lectin, combined with fluorine‐18 (
18
F) ([
18
F]FB‐rBC2LCN), resulted in reproducible, high‐contrast PET imaging of tumors in a PDAC xenograft mouse model. [
18
F]
N
‐succinimidyl‐4‐fluorobenzoate ([
18
F]SFB) was conjugated to rBC2LCN, and [
18
F]FB‐rBC2LCN was successfully prepared with a radiochemical purity >95%. Cell binding and uptake revealed that [
18
F]FB‐rBC2LCN binds to H‐type‐3‐positive Capan‐1 pancreatic cancer cells. As early as 60 min after [
18
F]FB‐rBC2LCN (0.34 ± 0.15 MBq) injection into the tail vein of nude mice subcutaneously bearing Capan‐1 tumors, tumor uptake was high (6.6 ± 1.8 %ID/g), and the uptake increased over time (8.8 ± 1.9 %ID/g and 11 ± 3.2 %ID/g at 150 and 240 min after injection, respectively). Tumor‐to‐muscle ratios increased over time, up to 19 ± 1.8 at 360 min. High‐contrast PET imaging of tumors relative to background muscle was also achieved as early as 60 min after injection of [
18
F]FB‐rBC2LCN (0.66 ± 0.12 MBq) and continued to increase up to 240 min. Our
18
F‐labeled rBC2LCN lectin warrants further clinical development to improve the accuracy and sensitivity of early‐stage pancreatic cancer detection. |
|---|---|
| AbstractList | Advancement in early detection modalities will greatly improve the overall prognoses of pancreatic ductal adenocarcinoma (PDAC). For this purpose, we report a novel class of tumor-specific probes for positron emission tomography (PET) based on targeting cell surface glycans. The PDAC-targeting ability of rBC2LCN lectin, combined with fluorine-18 (
F) ([
F]FB-rBC2LCN), resulted in reproducible, high-contrast PET imaging of tumors in a PDAC xenograft mouse model. [
F]N-succinimidyl-4-fluorobenzoate ([
F]SFB) was conjugated to rBC2LCN, and [
F]FB-rBC2LCN was successfully prepared with a radiochemical purity >95%. Cell binding and uptake revealed that [
F]FB-rBC2LCN binds to H-type-3-positive Capan-1 pancreatic cancer cells. As early as 60 min after [
F]FB-rBC2LCN (0.34 ± 0.15 MBq) injection into the tail vein of nude mice subcutaneously bearing Capan-1 tumors, tumor uptake was high (6.6 ± 1.8 %ID/g), and the uptake increased over time (8.8 ± 1.9 %ID/g and 11 ± 3.2 %ID/g at 150 and 240 min after injection, respectively). Tumor-to-muscle ratios increased over time, up to 19 ± 1.8 at 360 min. High-contrast PET imaging of tumors relative to background muscle was also achieved as early as 60 min after injection of [
F]FB-rBC2LCN (0.66 ± 0.12 MBq) and continued to increase up to 240 min. Our
F-labeled rBC2LCN lectin warrants further clinical development to improve the accuracy and sensitivity of early-stage pancreatic cancer detection. Advancement in early detection modalities will greatly improve the overall prognoses of pancreatic ductal adenocarcinoma (PDAC). For this purpose, we report a novel class of tumor-specific probes for positron emission tomography (PET) based on targeting cell surface glycans. The PDAC-targeting ability of rBC2LCN lectin, combined with fluorine-18 (18 F) ([18 F]FB-rBC2LCN), resulted in reproducible, high-contrast PET imaging of tumors in a PDAC xenograft mouse model. [18 F]N-succinimidyl-4-fluorobenzoate ([18 F]SFB) was conjugated to rBC2LCN, and [18 F]FB-rBC2LCN was successfully prepared with a radiochemical purity >95%. Cell binding and uptake revealed that [18 F]FB-rBC2LCN binds to H-type-3-positive Capan-1 pancreatic cancer cells. As early as 60 min after [18 F]FB-rBC2LCN (0.34 ± 0.15 MBq) injection into the tail vein of nude mice subcutaneously bearing Capan-1 tumors, tumor uptake was high (6.6 ± 1.8 %ID/g), and the uptake increased over time (8.8 ± 1.9 %ID/g and 11 ± 3.2 %ID/g at 150 and 240 min after injection, respectively). Tumor-to-muscle ratios increased over time, up to 19 ± 1.8 at 360 min. High-contrast PET imaging of tumors relative to background muscle was also achieved as early as 60 min after injection of [18 F]FB-rBC2LCN (0.66 ± 0.12 MBq) and continued to increase up to 240 min. Our 18 F-labeled rBC2LCN lectin warrants further clinical development to improve the accuracy and sensitivity of early-stage pancreatic cancer detection.Advancement in early detection modalities will greatly improve the overall prognoses of pancreatic ductal adenocarcinoma (PDAC). For this purpose, we report a novel class of tumor-specific probes for positron emission tomography (PET) based on targeting cell surface glycans. The PDAC-targeting ability of rBC2LCN lectin, combined with fluorine-18 (18 F) ([18 F]FB-rBC2LCN), resulted in reproducible, high-contrast PET imaging of tumors in a PDAC xenograft mouse model. [18 F]N-succinimidyl-4-fluorobenzoate ([18 F]SFB) was conjugated to rBC2LCN, and [18 F]FB-rBC2LCN was successfully prepared with a radiochemical purity >95%. Cell binding and uptake revealed that [18 F]FB-rBC2LCN binds to H-type-3-positive Capan-1 pancreatic cancer cells. As early as 60 min after [18 F]FB-rBC2LCN (0.34 ± 0.15 MBq) injection into the tail vein of nude mice subcutaneously bearing Capan-1 tumors, tumor uptake was high (6.6 ± 1.8 %ID/g), and the uptake increased over time (8.8 ± 1.9 %ID/g and 11 ± 3.2 %ID/g at 150 and 240 min after injection, respectively). Tumor-to-muscle ratios increased over time, up to 19 ± 1.8 at 360 min. High-contrast PET imaging of tumors relative to background muscle was also achieved as early as 60 min after injection of [18 F]FB-rBC2LCN (0.66 ± 0.12 MBq) and continued to increase up to 240 min. Our 18 F-labeled rBC2LCN lectin warrants further clinical development to improve the accuracy and sensitivity of early-stage pancreatic cancer detection. Advancement in early detection modalities will greatly improve the overall prognoses of pancreatic ductal adenocarcinoma (PDAC). For this purpose, we report a novel class of tumor‐specific probes for positron emission tomography (PET) based on targeting cell surface glycans. The PDAC‐targeting ability of rBC2LCN lectin, combined with fluorine‐18 ( 18 F) ([ 18 F]FB‐rBC2LCN), resulted in reproducible, high‐contrast PET imaging of tumors in a PDAC xenograft mouse model. [ 18 F] N ‐succinimidyl‐4‐fluorobenzoate ([ 18 F]SFB) was conjugated to rBC2LCN, and [ 18 F]FB‐rBC2LCN was successfully prepared with a radiochemical purity >95%. Cell binding and uptake revealed that [ 18 F]FB‐rBC2LCN binds to H‐type‐3‐positive Capan‐1 pancreatic cancer cells. As early as 60 min after [ 18 F]FB‐rBC2LCN (0.34 ± 0.15 MBq) injection into the tail vein of nude mice subcutaneously bearing Capan‐1 tumors, tumor uptake was high (6.6 ± 1.8 %ID/g), and the uptake increased over time (8.8 ± 1.9 %ID/g and 11 ± 3.2 %ID/g at 150 and 240 min after injection, respectively). Tumor‐to‐muscle ratios increased over time, up to 19 ± 1.8 at 360 min. High‐contrast PET imaging of tumors relative to background muscle was also achieved as early as 60 min after injection of [ 18 F]FB‐rBC2LCN (0.66 ± 0.12 MBq) and continued to increase up to 240 min. Our 18 F‐labeled rBC2LCN lectin warrants further clinical development to improve the accuracy and sensitivity of early‐stage pancreatic cancer detection. |
| Author | Tateno, Hiroaki Hatano, Kentaro Shimomura, Osamu Louphrasitthiphol, Pakavarin Kuroda, Yukihito Oda, Tatsuya Mathis, Bryan J. |
| Author_xml | – sequence: 1 givenname: Yukihito orcidid: 0000-0002-6920-6731 surname: Kuroda fullname: Kuroda, Yukihito organization: Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic Surgery, Faculty of Medicine University of Tsukuba Tsukuba Japan – sequence: 2 givenname: Tatsuya orcidid: 0000-0001-6115-0158 surname: Oda fullname: Oda, Tatsuya organization: Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic Surgery, Faculty of Medicine University of Tsukuba Tsukuba Japan – sequence: 3 givenname: Osamu surname: Shimomura fullname: Shimomura, Osamu organization: Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic Surgery, Faculty of Medicine University of Tsukuba Tsukuba Japan – sequence: 4 givenname: Pakavarin surname: Louphrasitthiphol fullname: Louphrasitthiphol, Pakavarin organization: Department of Gastrointestinal and Hepato‐Biliary‐Pancreatic Surgery, Faculty of Medicine University of Tsukuba Tsukuba Japan – sequence: 5 givenname: Bryan J. surname: Mathis fullname: Mathis, Bryan J. organization: International Medical Center University of Tsukuba Hospital Tsukuba Japan – sequence: 6 givenname: Hiroaki surname: Tateno fullname: Tateno, Hiroaki organization: Cellular and Molecular Biotechnology Research Institute National Institute of Advanced Industrial Science and Technology Tsukuba Japan – sequence: 7 givenname: Kentaro orcidid: 0000-0001-8154-3119 surname: Hatano fullname: Hatano, Kentaro organization: Department of Applied Molecular Imaging, Faculty of Medicine University of Tsukuba Tsukuba Japan |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/37203465$$D View this record in MEDLINE/PubMed |
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| Keywords | fluorine-18 pancreatic cancer molecular imaging lectin PET |
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| Snippet | Advancement in early detection modalities will greatly improve the overall prognoses of pancreatic ductal adenocarcinoma (PDAC). For this purpose, we report a... |
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| SubjectTerms | Animals Carcinoma, Pancreatic Ductal Cell Line, Tumor Humans Mice Mice, Nude Pancreatic Neoplasms Pancreatic Neoplasms - diagnostic imaging Positron-Emission Tomography - methods Radiopharmaceuticals |
| Title | Novel positron emission tomography imaging targeting cell surface glycans for pancreatic cancer: 18 F ‐labeled rBC2LCN lectin |
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