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Search: onr:"swepub:oai:DiVA.org:kth-75531" > Imaging of Human Ep...

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  • Heskamp, Sandra (author)

Imaging of Human Epidermal Growth Factor Receptor Type 2 Expression with (18)F-Labeled Affibody Molecule Z(HER2:2395) in a Mouse Model for Ovarian Cancer

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • 2011-12-15
  • Society of Nuclear Medicine,2012
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-75531
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-75531URI
  • https://doi.org/10.2967/jnumed.111.093047DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-164421URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20120206
  • Affibody molecules are small (7 kDa) proteins with subnanomolar targeting affinity. Previous SPECT studies in xenografts have shown that the Affibody molecule (111)In-DOTA-Z(HER2:2395) can discriminate between high and low human epidermal growth factor receptor type 2 (HER2)-expressing tumors, indicating that radiolabeled Affibody molecules have potential for patient selection for HER2-targeted therapy. Compared with SPECT, PET with positron-emitting radionuclides, such as (18)F, may improve imaging of HER2 expression because of higher sensitivity and improved quantification of PET. The aim of the present study was to determine whether the (18)F-labeled NOTA-conjugated Affibody molecule Z(HER2:2395) is a suitable agent for imaging of HER2 expression. The tumor-targeting properties of (18)F-labeled Z(HER2:2395) were compared with (111)In- and (68)Ga-labeled Z(HER2:2395) in mice with HER2-expressing SK-OV-3 xenografts. Methods: Z(HER2:2395) was conjugated with NOTA and radiolabeled with (18)F, (68)Ga, and (111)In. Radiolabeling with (18)F was based on the complexation of Al(18)F by NOTA. The 50% inhibitory concentration values for NOTA-Z(HER2:2395) labeled with (19)F, (69)Ga, and (115)In were determined in a competitive cell-binding assay using SK-OV-3 cells. Mice bearing subcutaneous SK-OV-3 xenografts were injected intravenously with radiolabeled NOTA-Z(HER2:2395). One and 4 h after injection, PET/CT or SPECT/CT images were acquired, and the biodistribution was determined by ex vivo measurement. Results: The 50% inhibitory concentration values for (19)F-, (69)Ga-, and (115)In-NOTA-Z(HER2:2395) were 5.0, 6.3, and 5.3 nM, respectively. One hour after injection, tumor uptake was 4.4 +/- 0.8 percentage injected dose per gram (% ID/g), 5.6 +/- 1.6 % ID/g, and 7.1 +/- 1.4 % ID/g for (18)F-, (68)Ga-, and (111)In-NOTA-Z(HER2:2395), respectively, and the respective tumor-to-blood ratios were 7.4 +/- 1.8, 8.0 +/- 1.3, and 4.8 +/- 1.3. Tumor uptake was specific, because uptake could be blocked efficiently by coinjection of an excess of unlabeled Z(HER2:2395). PET/CT and SPECT/CT images clearly visualized HER2-expressing SK-OV-3 xenografts. Conclusion: This study showed that (18)F-NOTA-Z(HER2:2395) is a promising new imaging agent for HER2 expression in tumors. Affibody molecules were successfully labeled with (18)F within 30 min, based on the complexation of Al(18)F by NOTA. Further research is needed to determine whether this technique can be used for patient selection for HER2-targeted therapy.

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  • Laverman, Peter (author)
  • Rosik, DanielKTH,Molekylär Bioteknologi(Swepub:kth)u1m2u8ne (author)
  • Boschetti, Frederic (author)
  • van der Graaf, Winette T. A. (author)
  • Oyen, Wim J. G. (author)
  • van Laarhoven, Hanneke W. M. (author)
  • Tolmachev, VladimirUppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Vladimir Tolmachev(Swepub:uu)vladtolm (author)
  • Boerman, Otto C. (author)
  • KTHMolekylär Bioteknologi (creator_code:org_t)

Related titles

  • In:Journal of Nuclear Medicine: Society of Nuclear Medicine53:1, s. 146-1530161-55051535-56672159-662X

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