First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study
Abstract Background Following resection and standard adjuvant radio- and chemotherapy, approved maintenance therapies for glioblastoma are lacking. Intracavitary radioimmunotherapy (iRIT) with 177Lu-labeled 6A10-Fab fragments targeting tumor-associated carbonic anhydrase XII and injected into the re...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-09-01
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| Series: | EJNMMI Research |
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| Online Access: | https://doi.org/10.1186/s13550-023-01029-7 |
| _version_ | 1797451535042478080 |
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| author | Wolfgang Roll Michael Müther Guido Böning Astrid Delker Nils Warneke Franz-Josef Gildehaus Michael Schäfers Walter Stummer Reinhard Zeidler Hans-Jürgen Reulen Lars Stegger |
| author_facet | Wolfgang Roll Michael Müther Guido Böning Astrid Delker Nils Warneke Franz-Josef Gildehaus Michael Schäfers Walter Stummer Reinhard Zeidler Hans-Jürgen Reulen Lars Stegger |
| author_sort | Wolfgang Roll |
| collection | DOAJ |
| description | Abstract Background Following resection and standard adjuvant radio- and chemotherapy, approved maintenance therapies for glioblastoma are lacking. Intracavitary radioimmunotherapy (iRIT) with 177Lu-labeled 6A10-Fab fragments targeting tumor-associated carbonic anhydrase XII and injected into the resection cavity offers a novel and promising strategy for improved tumor control. Methods Three glioblastoma patients underwent tumor resection followed by standard radio- and chemotherapy. These patients with stable disease following completion of standard therapy underwent iRIT on compassionate grounds. After surgical implantation of a subcutaneous injection reservoir with a catheter into the resection cavity, a leakage test with [99mTc]Tc-DTPA was performed to rule out leakage into other cerebral compartments. IRIT comprised three consecutive applications over three months for each patient, with 25%, 50%, 25% of the total activity injected. A dosimetry protocol was included with blood sampling and SPECT/CT of the abdomen to calculate doses for the bone marrow and kidneys as potential organs at risk. Results All three patients presented without relevant leakage after application of [99mTc]Tc-DTPA. Two patients underwent three full cycles of iRIT (592 MBq and 1228 MBq total activity). One patient showed histologically proven tumor progression after the second cycle (526 MBq total activity). No relevant therapy-associated toxicities or adverse events were observed. Dosimetry did not reveal absorbed doses above upper dose limits for organs at risk. Conclusions In first individual cases, iRIT with [177Lu]Lu-6A10-Fab appears to be feasible and safe, without therapy-related side effects. A confirmatory multicenter phase-I-trial was recently opened and is currently recruiting. |
| first_indexed | 2024-03-09T14:55:05Z |
| format | Article |
| id | doaj.art-4b7795c149c041df88ca457cecc3e060 |
| institution | Directory Open Access Journal |
| issn | 2191-219X |
| language | English |
| last_indexed | 2024-03-09T14:55:05Z |
| publishDate | 2023-09-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Research |
| spelling | doaj.art-4b7795c149c041df88ca457cecc3e0602023-11-26T14:12:28ZengSpringerOpenEJNMMI Research2191-219X2023-09-011311810.1186/s13550-023-01029-7First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot studyWolfgang Roll0Michael Müther1Guido Böning2Astrid Delker3Nils Warneke4Franz-Josef Gildehaus5Michael Schäfers6Walter Stummer7Reinhard Zeidler8Hans-Jürgen Reulen9Lars Stegger10Department of Nuclear Medicine, University Hospital MünsterWest German Cancer CentreDepartment of Nuclear Medicine, University Hospital, Ludwig-Maximilians-University MunichDepartment of Nuclear Medicine, University Hospital, Ludwig-Maximilians-University MunichWest German Cancer CentreDepartment of Nuclear Medicine, University Hospital, Ludwig-Maximilians-University MunichDepartment of Nuclear Medicine, University Hospital MünsterWest German Cancer CentreDepartment of Otorhinolaryngology, University Hospital, Ludwig-Maximilians-University MunichDepartment of Neurosurgery, University Hospital, Ludwig-Maximilians-University MunichDepartment of Nuclear Medicine, University Hospital MünsterAbstract Background Following resection and standard adjuvant radio- and chemotherapy, approved maintenance therapies for glioblastoma are lacking. Intracavitary radioimmunotherapy (iRIT) with 177Lu-labeled 6A10-Fab fragments targeting tumor-associated carbonic anhydrase XII and injected into the resection cavity offers a novel and promising strategy for improved tumor control. Methods Three glioblastoma patients underwent tumor resection followed by standard radio- and chemotherapy. These patients with stable disease following completion of standard therapy underwent iRIT on compassionate grounds. After surgical implantation of a subcutaneous injection reservoir with a catheter into the resection cavity, a leakage test with [99mTc]Tc-DTPA was performed to rule out leakage into other cerebral compartments. IRIT comprised three consecutive applications over three months for each patient, with 25%, 50%, 25% of the total activity injected. A dosimetry protocol was included with blood sampling and SPECT/CT of the abdomen to calculate doses for the bone marrow and kidneys as potential organs at risk. Results All three patients presented without relevant leakage after application of [99mTc]Tc-DTPA. Two patients underwent three full cycles of iRIT (592 MBq and 1228 MBq total activity). One patient showed histologically proven tumor progression after the second cycle (526 MBq total activity). No relevant therapy-associated toxicities or adverse events were observed. Dosimetry did not reveal absorbed doses above upper dose limits for organs at risk. Conclusions In first individual cases, iRIT with [177Lu]Lu-6A10-Fab appears to be feasible and safe, without therapy-related side effects. A confirmatory multicenter phase-I-trial was recently opened and is currently recruiting.https://doi.org/10.1186/s13550-023-01029-7RadioimmunotherapyCarbonic anhydrase XIIImmunoglobulin Fab fragmentsGlioblastomaLutetium-177 |
| spellingShingle | Wolfgang Roll Michael Müther Guido Böning Astrid Delker Nils Warneke Franz-Josef Gildehaus Michael Schäfers Walter Stummer Reinhard Zeidler Hans-Jürgen Reulen Lars Stegger First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study EJNMMI Research Radioimmunotherapy Carbonic anhydrase XII Immunoglobulin Fab fragments Glioblastoma Lutetium-177 |
| title | First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study |
| title_full | First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study |
| title_fullStr | First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study |
| title_full_unstemmed | First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study |
| title_short | First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study |
| title_sort | first clinical experience with fractionated intracavitary radioimmunotherapy using 177lu lu 6a10 fab fragments in patients with glioblastoma a pilot study |
| topic | Radioimmunotherapy Carbonic anhydrase XII Immunoglobulin Fab fragments Glioblastoma Lutetium-177 |
| url | https://doi.org/10.1186/s13550-023-01029-7 |
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