ArticleDalton transactions (Cambridge, England : 2003)2014
H6phospa-trastuzumab: bifunctional methylenephosphonate-based chelator with 89Zr, 111In and 177Lu.
Article in Dalton transactions (Cambridge, England : 2003), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Biodistribution, dosimetry, and temporal signal-to-noise ratio analyses of normal and cancer uptake of [Nuclear medicine and biologyTrial
- Dipicolinic acid (DPA)-based chelators for zirconium-89 PET imaging applications.Bioorganic & medicinal chemistry letters · 2026Article
- The Evaluation of (1Molecules (Basel, Switzerland) · 2025Article
- Development of a multi faceted platform containing a tetrazine, fluorophore and chelator: synthesis, characterization, radiolabeling, and immuno-SPECT imaging.EJNMMI radiopharmacy and chemistry · 2022Article
- The Race for Hydroxamate-Based Zirconium-89 Chelators.Cancers · 2021Review
- Polyazamacrocycle Ligands FacilitateInorganic chemistry · 2020Article
- A High-Denticity Chelator Based on Desferrioxamine for Enhanced Coordination of Zirconium-89.Inorganic chemistry · 2020Article
- Production and Semi-Automated Processing ofMolecules (Basel, Switzerland) · 2020Article
- ImmunoPET: Concept, Design, and Applications.Chemical reviews · 2020Review
- Oxyaapa: A Picolinate-Based Ligand with Five Oxygen Donors that Strongly Chelates Lanthanides.Inorganic chemistry · 2020Article
- Rod-shape theranostic nanoparticles facilitate antiretroviral drug biodistribution and activity in human immunodeficiency virus susceptible cells and tissues.Theranostics · 2020Article
- Evaluation of polydentate picolinic acid chelating ligands and an α-melanocyte-stimulating hormone derivative for targeted alpha therapy using ISOL-producedEJNMMI radiopharmacy and chemistry · 2019Article
- Article
- Recent Advances in Zirconium-89 Chelator Development.Molecules (Basel, Switzerland) · 2018Review
- Review
- Investigation of the complexation ofDalton transactions (Cambridge, England : 2003) · 2017Article
- Zirconium tetraazamacrocycle complexes display extraordinary stability and provide a new strategy for zirconium-89-based radiopharmaceutical development.Chemical science · 2017Article
- Comparison of the octadentate bifunctional chelator DFO*-pPhe-NCS and the clinically used hexadentate bifunctional chelator DFO-pPhe-NCS forEuropean journal of nuclear medicine and molecular imaging · 2017Article
- Evaluation of macrocyclic hydroxyisophthalamide ligands as chelators for zirconium-89.PloS one · 2017Article
- p-SCN-Bn-HOPO: A Superior Bifunctional Chelator for (89)Zr ImmunoPET.Bioconjugate chemistry · 2015Article
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5 authors.
Funding
Abstract
The acyclic chelator H6phospa and the bifunctional derivative p-SCN-Bn-H6phospa have been synthesized using nosyl protection chemistry and evaluated with (89)Zr, (111)In, and (177)Lu. The p-SCN-Bn-H6phospa derivative was successfully conjugated to trastuzumab with isotopic dilution assays indicating 3.3 ± 0.1 chelates per antibody and in vitro cellular binding assays indicating an immunoreactivity value of 97.9 ± 2.6%. Radiolabeling of the H6phospa-trastuzumab immunoconjugate was achieved with (111)In in 70-90% yields at room temperature in 30 minutes, while (177)Lu under the same conditions produced more inconsistent yields of 40-80%. Stability experiments in human serum revealed the (111)In-phospa-trastuzumab complex to be 52.0 ± 5.3% intact after 5 days at 37 °C, while the (177)Lu-phospa-trastuzumab to be only 2.0 ± 0.3% intact. Small animal SPECT/CT imaging using mice bearing subcutaneous SKOV-3 ovarian cancer xenografts was performed, and it was found that (111)In-phospa-trastuzumab successfully identified and delineated small (~2 mm in diameter) tumors from surrounding tissues, despite visible uptake in the kidneys and bone due to moderate chelate instability. As predicted from stability assays in serum, the (177)Lu-phospa-trastuzumab conjugate served as a negative control and displayed no tumor uptake, with high uptake in bones indicating rapid and complete radiometal dissociation and suggesting a potential application of H6phospa in transient lanthanide chelation for bone-delivery. Radiolabeling with (89)Zr was attempted, but even with elevated temperatures of 37 °C, the maximum observed radiometal incorporation over 18 hours was 12%. It can be concluded from this work that H6phospa is not superior to the previously studied H4octapa for use with (111)In and (177)Lu, but improvements in (89)Zr radiolabeling were observed over H4octapa, suggesting H6phospa to be an excellent starting point for elaboration of (89)Zr-based radiopharmaceutical development. To our knowledge, H6phospa is the best desferrioxamine alternative for (89)Zr radiolabeling to be studied to date.
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