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

LIBRIS Formathandbok  (Information om MARC21)
00004537naa a2200469 4500
008120206s2012 | |||||||||||000 ||eng|
024a urn:nbn:se:kth:diva-755312 urn
024a https://doi.org/10.2967/jnumed.111.0930472 DOI
040 a (SwePub)kth
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
100a Heskamp, Sandra4 aut
2451 0a 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
264 1c 2012
338 a print2 rdacarrier
500 a QC 20120206
520 a 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.
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Radiology, Nuclear Medicine and Medical Imaging0 (SwePub)302082 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Radiologi och bildbehandling0 (SwePub)302082 hsv//swe
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicin0 (SwePub)3022 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicine0 (SwePub)3022 hsv//eng
653 a HER2
653 a Affibody molecule
653 a PET
653 a (18)F
653 a ovarian cancer
700a Laverman, Peter4 aut
700a Rosik, Danielu KTH,Molekylär Bioteknologi (stängd 20130101)4 aut0 (Swepub:kth)u1m2u8ne
700a Boschetti, Frederic4 aut
700a van der Graaf, Winette T. A.4 aut
700a Oyen, Wim J. G.4 aut
700a van Laarhoven, Hanneke W. M.4 aut
700a Tolmachev, Vladimir4 aut
700a Boerman, Otto C.4 aut
710a KTHb Molekylär Bioteknologi (stängd 20130101)4 org
773t Journal of Nuclear Medicineg 53:1, s. 146-153q 53:1<146-153x 0161-5505x 1535-5667
8564 8u http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-75531x lärosäteslänky Till lärosätets (kth) databas
8564 8u https://doi.org/10.2967/jnumed.111.093047

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