Preclinical evaluation and automated synthesis of [89Zr]ZrDFOSquaramide-girentuximab for diagnostic imaging of carbonic anhydrase IX positive tumours

Noor, A; McGowan, ER; Van Zuylekom, JK; Cullinane, C; Roselt, PD; Hicks, RJ; Wheatcroft, MP; Donnelly, PS

Author(s): Noor, A; McGowan, ER; Van Zuylekom, JK; Cullinane, C; Roselt, PD; Hicks, RJ; Wheatcroft, MP; Donnelly, PS;
Details: Publication Year 2024-11-26,Volume 9,Issue #1,Page 80
Journal Title: EJNMMI Radiopharmacy and Chemistry
Publication Type: Research article
Abstract: BACKGROUND: Carbonic Anhydrase IX (CAIX) is a zinc metalloenzyme that is over-expressed in many cancers making it a valid target for targeted diagnostic imaging with Positron Emission Tomography (PET). The monoclonal antibody girentuximab binds to CAIX and when radiolabelled with positron-emitting zirconium-89 can be used for diagnostic PET imaging of CAIX positive tumours. RESULTS: Reaction of desferrioxamine squaramide ethyl ester with girentuximab allowed isolation of a conjugate with desferrioxamine squaramide (DFOSq) covalently attached to girentuximab through stable vinylogous amide linkages to give DFOSq-girentuximab. This conjugate was radiolabelled with zirconium-89 to give [(89)Zr]ZrDFOSq-girentuximab and the tumour uptake of the tracer was evaluated in CAIX positive HT29 tumour-bearing mice. Analysis of the PET images and biodistribution studies showed that the tracer displays high tumour uptake. An automated process for production of [(89)Zr]ZrDFOSq-girentuximab was developed, using [(89)Zr]ZrCl(4) as a starting material that was also synthesized in an automated process. This automated process allows isolation of [(89)Zr]ZrDFOSq-girentuximab in radiochemical yields of 80-90% and in > 95% radiochemical purity. CONCLUSIONS: [(89)Zr]ZrDFOSq-girentuximab has high uptake in CAIX positive tumours. An automated procedure for the synthesis of [(89)Zr]ZrDFOSq-girentuximab using [(89)Zr]ZrCl(4) as a starting material has been developed. This automated process could be readily adapted to other antibodies.
Publisher: Springer Nature
Keywords: Automated synthesis; Carbonic anhydrase IX; DFO-squaramide; Girentuximab; Radiopharmaceuticals; Zirconium-89; Zirconium-89 labelled antibodies
Department(s): Laboratory Research; Cancer Imaging
Publisher's Version: https://doi.org/10.1186/s41181-024-00310-x
Open Access at Publisher's Site: https://doi.org/10.1186/s41181-024-00310-x
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-12-17 06:20:10

Last Modified: 2024-12-17 06:26:01