Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging
Abstract Background Pretargeted imaging allows the use of short-lived radionuclides when imaging the accumulation of slow clearing targeting agents such as antibodies. The biotin-(strept)avidin and the bispecific antibody-hapten interactions have been applied in clinical pretargeting studies; unfort...
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| Fformat: | Erthygl |
| Iaith: | English |
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SpringerOpen
2019-05-01
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| Cyfres: | EJNMMI Research |
| Pynciau: | |
| Mynediad Ar-lein: | http://link.springer.com/article/10.1186/s13550-019-0520-y |
| _version_ | 1828760739562651648 |
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| author | Patricia E. Edem Jean-Philippe Sinnes Stefanie Pektor Nicole Bausbacher Raffaella Rossin Abdolreza Yazdani Matthias Miederer Andreas Kjær John F. Valliant Marc S. Robillard Frank Rösch Matthias M. Herth |
| author_facet | Patricia E. Edem Jean-Philippe Sinnes Stefanie Pektor Nicole Bausbacher Raffaella Rossin Abdolreza Yazdani Matthias Miederer Andreas Kjær John F. Valliant Marc S. Robillard Frank Rösch Matthias M. Herth |
| author_sort | Patricia E. Edem |
| collection | DOAJ |
| description | Abstract Background Pretargeted imaging allows the use of short-lived radionuclides when imaging the accumulation of slow clearing targeting agents such as antibodies. The biotin-(strept)avidin and the bispecific antibody-hapten interactions have been applied in clinical pretargeting studies; unfortunately, these systems led to immunogenic responses in patients. The inverse electron demand Diels-Alder (IEDDA) reaction between a radiolabelled tetrazine (Tz) and a trans-cyclooctene (TCO)-functionalized targeting vector is a promising alternative for clinical pretargeted imaging due to its fast reaction kinetics. This strategy was first applied in nuclear medicine using an 111In-labelled Tz to image TCO-functionalized antibodies in tumour-bearing mice. Since then, the IEDDA has been used extensively in pretargeted nuclear imaging and radiotherapy; however, these studies have only been performed in mice. Herein, we report the 44Sc labelling of a Tz and evaluate it in pretargeted imaging in Wistar rats. Results 44Sc was obtained from an in house 44Ti/44Sc generator. A 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-functionalized tetrazine was radiolabelled with 44Sc resulting in radiochemical yields of 85–95%, a radiochemical purity > 99% at an apparent molar activity of 1 GBq/mmol. The 44Sc-labelled Tz maintained stability in solution for up to 24 h. A TCO-functionalized bisphosphonate, which accumulates in skeletal tissue, was used as a targeting vector to evaluate the 44Sc-labelled Tz. Biodistribution data of the 44Sc-labelled Tz showed specific uptake (0.9 ± 0.3% ID/g) in the bones (humerus and femur) of rats pre-treated with the TCO-functionalized bisphosphonate. This uptake was not present in rats not receiving pre-treatment (< 0.03% ID/g). Conclusions We have prepared a 44Sc-labelled Tz and used it in pretargeted PET imaging with rats treated with TCO-functionalized bisphosponates. This allowed for the evaluation of the IEDDA reaction in animals larger than a typical mouse. Non-target accumulation was low, and there was a 30-fold higher bone uptake in the pre-treated rats compared to the non-treated controls. Given its convenient half-life and the ability to perform positron emission tomography with a previously studied DOTA-functionalized Tz, scandium-44 (t 1/2 = 3.97 h) proved to be a suitable radioisotope for this study. |
| first_indexed | 2024-12-11T01:18:24Z |
| format | Article |
| id | doaj.art-3c3a2b2c7f3b4c0690ccc0893c5a719d |
| institution | Directory Open Access Journal |
| issn | 2191-219X |
| language | English |
| last_indexed | 2024-12-11T01:18:24Z |
| publishDate | 2019-05-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Research |
| spelling | doaj.art-3c3a2b2c7f3b4c0690ccc0893c5a719d2022-12-22T01:25:48ZengSpringerOpenEJNMMI Research2191-219X2019-05-01911810.1186/s13550-019-0520-yEvaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imagingPatricia E. Edem0Jean-Philippe Sinnes1Stefanie Pektor2Nicole Bausbacher3Raffaella Rossin4Abdolreza Yazdani5Matthias Miederer6Andreas Kjær7John F. Valliant8Marc S. Robillard9Frank Rösch10Matthias M. Herth11Department of Clinical Physiology, Nuclear Medicine & PET, RigshospitaletJohannes Gutenberg-Universität MainzUniversity Medical Center MainzUniversity Medical Center MainzTagworks PharmaceuticalsMcMaster UniversityUniversity Medical Center MainzDepartment of Clinical Physiology, Nuclear Medicine & PET, RigshospitaletMcMaster UniversityTagworks PharmaceuticalsJohannes Gutenberg-Universität MainzDepartment of Clinical Physiology, Nuclear Medicine & PET, RigshospitaletAbstract Background Pretargeted imaging allows the use of short-lived radionuclides when imaging the accumulation of slow clearing targeting agents such as antibodies. The biotin-(strept)avidin and the bispecific antibody-hapten interactions have been applied in clinical pretargeting studies; unfortunately, these systems led to immunogenic responses in patients. The inverse electron demand Diels-Alder (IEDDA) reaction between a radiolabelled tetrazine (Tz) and a trans-cyclooctene (TCO)-functionalized targeting vector is a promising alternative for clinical pretargeted imaging due to its fast reaction kinetics. This strategy was first applied in nuclear medicine using an 111In-labelled Tz to image TCO-functionalized antibodies in tumour-bearing mice. Since then, the IEDDA has been used extensively in pretargeted nuclear imaging and radiotherapy; however, these studies have only been performed in mice. Herein, we report the 44Sc labelling of a Tz and evaluate it in pretargeted imaging in Wistar rats. Results 44Sc was obtained from an in house 44Ti/44Sc generator. A 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-functionalized tetrazine was radiolabelled with 44Sc resulting in radiochemical yields of 85–95%, a radiochemical purity > 99% at an apparent molar activity of 1 GBq/mmol. The 44Sc-labelled Tz maintained stability in solution for up to 24 h. A TCO-functionalized bisphosphonate, which accumulates in skeletal tissue, was used as a targeting vector to evaluate the 44Sc-labelled Tz. Biodistribution data of the 44Sc-labelled Tz showed specific uptake (0.9 ± 0.3% ID/g) in the bones (humerus and femur) of rats pre-treated with the TCO-functionalized bisphosphonate. This uptake was not present in rats not receiving pre-treatment (< 0.03% ID/g). Conclusions We have prepared a 44Sc-labelled Tz and used it in pretargeted PET imaging with rats treated with TCO-functionalized bisphosponates. This allowed for the evaluation of the IEDDA reaction in animals larger than a typical mouse. Non-target accumulation was low, and there was a 30-fold higher bone uptake in the pre-treated rats compared to the non-treated controls. Given its convenient half-life and the ability to perform positron emission tomography with a previously studied DOTA-functionalized Tz, scandium-44 (t 1/2 = 3.97 h) proved to be a suitable radioisotope for this study.http://link.springer.com/article/10.1186/s13550-019-0520-yScandium-44 (44Sc)Positron emission tomography (PET)TetrazineTrans-cyclooctene (TCO)Pretargeted imagingInverse electron demand Diels-Alder (IEDDA) |
| spellingShingle | Patricia E. Edem Jean-Philippe Sinnes Stefanie Pektor Nicole Bausbacher Raffaella Rossin Abdolreza Yazdani Matthias Miederer Andreas Kjær John F. Valliant Marc S. Robillard Frank Rösch Matthias M. Herth Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging EJNMMI Research Scandium-44 (44Sc) Positron emission tomography (PET) Tetrazine Trans-cyclooctene (TCO) Pretargeted imaging Inverse electron demand Diels-Alder (IEDDA) |
| title | Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging |
| title_full | Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging |
| title_fullStr | Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging |
| title_full_unstemmed | Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging |
| title_short | Evaluation of the inverse electron demand Diels-Alder reaction in rats using a scandium-44-labelled tetrazine for pretargeted PET imaging |
| title_sort | evaluation of the inverse electron demand diels alder reaction in rats using a scandium 44 labelled tetrazine for pretargeted pet imaging |
| topic | Scandium-44 (44Sc) Positron emission tomography (PET) Tetrazine Trans-cyclooctene (TCO) Pretargeted imaging Inverse electron demand Diels-Alder (IEDDA) |
| url | http://link.springer.com/article/10.1186/s13550-019-0520-y |
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