Positron emission tomography (PET) imaging of neuroblastoma and melanoma with 64Cu-SarAr immunoconjugates

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dc.contributor.authorVoss, SDen_AU
dc.contributor.authorSmith, SVen_AU
dc.contributor.authorDiBartolo, Nen_AU
dc.contributor.authorMcIntosh, LJen_AU
dc.contributor.authorCyr, EMen_AU
dc.contributor.authorBonab, AAen_AU
dc.contributor.authorDearling, JLJen_AU
dc.contributor.authorCarter, EAen_AU
dc.contributor.authorFischman, AJen_AU
dc.contributor.authorTreves, STen_AU
dc.contributor.authorGillies, SDen_AU
dc.contributor.authorSargeson, AMen_AU
dc.contributor.authorHuston, JSen_AU
dc.contributor.authorPackard, ABen_AU
dc.date.accessioned2010-10-21T02:55:25Zen_AU
dc.date.available2010-10-21T02:55:25Zen_AU
dc.date.issued2007-10-30en_AU
dc.date.statistics2007-10-30en_AU
dc.description.abstractThe advancement of positron emission tomography (PET) depends on the development of new radiotracers that will complement 18F-FDG. Copper-64 (64Cu) is a promising PET radionuclide, particularly for antibody-targeted imaging, but the high in vivo lability of conventional chelates has limited its clinical application. The objective of this work was to evaluate the novel chelating agent SarAr (1-N-(4-aminobenzyl)-3, 6,10,13,16,19-hexaazabicyclo[6.6.6] eicosane-1,8-diamine) for use in developing a new class of tumor-specific 64Cu radiopharmaceuticals for imaging neuroblastoma and melanoma. The anti-GD2 monoclonal antibody (mAb) 14.G2a, and its chimeric derivative, ch14.18, target disialogangliosides that are overexpressed on neuroblastoma and melanoma. Both mAbs were conjugated to SarAr using carbodiimide coupling. Radiolabeling with 64Cu resulted in >95% of the 64Cu being chelated by the immunoconjugate. Specific activities of at least 10 μCi/μg (1 Ci = 37 GBq) were routinely achieved, and no additional purification was required after 64Cu labeling. Solid-phase radioimmunoassays and intact cell-binding assays confirmed retention of bioactivity. Biodistribution studies in athymic nude mice bearing s.c. neuroblastoma (IMR-6, NMB-7) and melanoma (M21) xenografts showed that 15–20% of the injected dose per gram accumulated in the tumor at 24 hours after injection, and only 5–10% of the injected dose accumulated in the liver, a lower value than typically seen with other chelators. Uptake by a GD2-negative tumor xenograft was significantly lower (<5% injected dose per gram). MicroPET imaging confirmed significant uptake of the tracer in GD-2-positive tumors, with minimal uptake in GD-2-negative tumors and nontarget tissues such as liver. The 64Cu-SarAr-mAb system described here is potentially applicable to 64Cu-PET imaging with a broad range of antibody or peptide-based imaging agents. © 2007, National Academy of Sciencesen_AU
dc.identifier.citationVoss, S. D., Smith, S. V., DiBartolo, N., McLntos, L. J., Cyr, E. M., Bonab, A. A., Dearling, J. L. J., Carter, E. A., Fischman, A. J., Treves, S. T., Gillies, S. D., Sargeson, A. M., Huston, J. S., & Packard, A. B. (2007). Positron emission tomography (PET) imaging of neuroblastoma and melanoma with Cu-64-SarAr immunoconjugates. Proceedings of the National Academy of Sciences, 104(44), 17489-17493. doi:10.1073/pnas.0708436104en_AU
dc.identifier.govdoc2883en_AU
dc.identifier.issn0027-8424en_AU
dc.identifier.issue44en_AU
dc.identifier.journaltitleProceedings of the National Academy of Sciencesen_AU
dc.identifier.pagination17489-17493en_AU
dc.identifier.urihttp://dx.doi.org/10.1073/pnas.0708436104en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/2722en_AU
dc.identifier.volume104en_AU
dc.language.isoenen_AU
dc.publisherNational Academy of Sciencesen_AU
dc.subjectPositron computed tomographyen_AU
dc.subjectMelanomasen_AU
dc.subjectTracer techniquesen_AU
dc.subjectRadiopharmaceuticalsen_AU
dc.subjectNeoplasmsen_AU
dc.subjectCopper 64en_AU
dc.titlePositron emission tomography (PET) imaging of neuroblastoma and melanoma with 64Cu-SarAr immunoconjugatesen_AU
dc.typeJournal Articleen_AU
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