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| Content Provider | PubMed Central |
|---|---|
| Author | Price, Eric W. Zeglis, Brian M. Lewis, Jason S. Adam, Michael J. Orvig, Chris |
| Abstract | The acyclic chelator H6phospa and the bifunctional derivativep-SCN-Bn-H6phospa have been synthesized usingnosyl protection chemistry and evaluated with 89Zr, 111In,and 177Lu. The p-SCN-Bn-H6phospaderivative was successfully conjugated to trastuzumab with isotopic dilutionassays indicating 3.3 ± 0.1 chelates per antibody and invitro cellular binding assays indicating an immunoreactivity valueof 97.9 ± 2.6%. Radiolabeling of theH6phospa-trastuzumab immunoconjugate was achieved with111In in 70–90% yields at room temperature in 30minutes, while 177Lu under the same conditions produced moreinconsistent yields of 40–80%. Stability experiments in humanserum revealed the 111In-phospa-trastuzumab complex to be 52.0± 5.3% intact after 5 days at 37 °C, while the177Lu-phospa-trastuzumab to be only 2.0 ± 0.3%intact. Small animal SPECT/CT imaging using mice bearing subcutaneous SKOV-3ovarian cancer xenografts was performed, and it was found that111In-phospa-trastuzumab successfully identified and delineated small(~2 mm in diameter) tumors from surrounding tissues, despite visibleuptake in the kidneys and bone due to moderate chelate instability. As predictedfrom stability assays in serum, the 177Lu-phospa-trastuzumabconjugate served as a negative control and displayed no tumor uptake, with highuptake in bones indicating rapid and complete radiometal dissociation andsuggesting a potential application of H6phospa in transientlanthanide chelation for bone-delivery. Radiolabeling with 89Zr wasattempted, but even with elevated temperatures of 37 °C, the maximumobserved radiometal incorporation over 18 hours was 12%. It can beconcluded from this work that H6phospa is not superior to thepreviously studied H4octapa for use with 111In and177Lu, but improvements in 89Zr radiolabeling wereobserved over H4octapa, suggesting H6phospa to be anexcellent starting point for elaboration of 89Zr-basedradiopharmaceutical development. To our knowledge, H6phospa is thebest desferrioxamine alternative for 89Zr radiolabeling to be studiedto date. |
| Related Links | http://dx.doi.org/10.1039/c3dt51940f |
| Ending Page | 131 |
| Page Count | 13 |
| Starting Page | 119 |
| File Format | |
| ISSN | 14779226 |
| e-ISSN | 14779234 |
| Journal | Dalton transactions (Cambridge, England : 2003) |
| Issue Number | 1 |
| Volume Number | 43 |
| Language | English |
| Publisher Date | 2014-01-01 |
| Access Restriction | Open |
| Subject Keyword | Inorganic Chemistry Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Inorganic Chemistry |
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