Preparation of <superscript>177</superscript>Lu‐labeled Nimotuzumab for radioimmunotherapy of EGFR‐positive cancers: Comparison of DOTA and CHX‐A″‐DTPA as bifunctional chelators.
In: Journal of Labelled Compounds & Radiopharmaceuticals, Jg. 62 (2019-04-15), Heft 4, S. 158-165
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Zugriff:
This study was aimed at evaluating the role of bifunctional chelators DOTA‐NCS and CHX‐A″‐DTPA‐NCS used for conjugating 177Lu with Nimotuzumab on the radiochemical yields, purity, in vitro stability, and specificity of the radioimmunoconjugates to EGFR. Two immunoconjugates were prepared wherein Nimotuzumab was conjugated with the acyclic ligand p‐NCS‐Bn‐CHX‐A″‐DTPA and macrocyclic ligand p‐NCS‐Bn‐DOTA. These were radiolabeled with 177Lu, purified on PD‐10 column, and characterized by SE‐HPLC. In vitro stability was determined up to 4 days post preparation. Specificity of the radioimmunoconjugates was ascertained by in vitro studies in A431 cells while the biodistribution patterns were studied in normal Swiss mice up to 96 hours post injection. Four to five molecules of CHX‐A″‐DTPA/DOTA were attached to one molecule of Nimotuzumab. Radiochemical purity of both 177Lu‐CHX‐A″‐DTPA‐Nimotuzumab and 177Lu‐DOTA‐Nimotuzumab was determined to be greater than 98%. Both the radioimmunoconjugates exhibited good in vitro stability at 37°C up to 4 days post preparation in saline, and their clearance was largely by the hepatobiliary route. The DOTA‐ and CHX‐A″‐DTPA‐based radioimmunoconjugates could be prepared with good radiochemical purity, in vitro stability, and specificity to EGFR. Further studies in EGFR‐positive cancers would pave way for them for use in the clinics. The two immunoconjugates of nimotuzumab prepared by conjugation with the acyclic ligand p‐NCS‐Bn‐CHX‐A″‐DTPA and macrocyclic ligand p‐NCS‐Bn‐DOTA were labeled with 177Lu. The specificity of the two radioimmunoconjugates was ascertained by in vitro studies in A431 cells. [ABSTRACT FROM AUTHOR]
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Titel: |
Preparation of <superscript>177</superscript>Lu‐labeled Nimotuzumab for radioimmunotherapy of EGFR‐positive cancers: Comparison of DOTA and CHX‐A″‐DTPA as bifunctional chelators.
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Autor/in / Beteiligte Person: | Pandey, Usha ; Kameswaran, Mythili ; Gamre, Naresh ; Dash, Ashutosh |
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Zeitschrift: | Journal of Labelled Compounds & Radiopharmaceuticals, Jg. 62 (2019-04-15), Heft 4, S. 158-165 |
Veröffentlichung: | 2019 |
Medientyp: | academicJournal |
ISSN: | 0362-4803 (print) |
DOI: | 10.1002/jlcr.3707 |
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