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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005840naa a2200613 4500
001oai:DiVA.org:kth-117890
003SwePub
008130206s2014 | |||||||||||000 ||eng|
009oai:DiVA.org:uu-218569
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-1178902 URI
0247 a https://doi.org/10.1021/bc400343r2 DOI
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2185692 URI
040 a (SwePub)kthd (SwePub)uu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Rosik, Danielu KTH,Proteinteknologi4 aut0 (Swepub:kth)u1m2u8ne
2451 0a Incorporation of a Triglutamyl Spacer Improves the Biodistribution of Synthetic Affibody Molecules Radiofluorinated at the N-Terminus via Oxime Formation with F-18-4-Fluorobenzaldehyde
264 c 2013-12-27
264 1b American Chemical Society (ACS),c 2014
338 a print2 rdacarrier
500 a QC 20140221. Updated from manuscript to article in journal.
520 a Affibody molecules are a class of affinity agents for molecular imaging based on a non-immunoglobulin protein scaffold. Previous studies have demonstrated high contrast for in vivo imaging of cancer-associated molecular abnormalities using Affibody molecules. Using the radionuclide F-18 for labeling and PET as the imaging modality, the sensitivity of molecular imaging using Affibody molecules can be further increased. The use of oxime formation between an aminooxy-functionalized peptide and F-18-fluorobenzaldehyde (F-18-FBA) is a promising way of radiolabeling of targeting peptides. However, previous studies demonstrated that application of this method to Affibody molecules is associated with high liver uptake. We hypothesized that incorporation of a triglutamyl spacer between the aminooxy moiety and the N-terminus of a synthetic Affibody molecule would decrease the hepatic uptake of the F-18-N-(4-fluorobenzylidine)oxime) (F-18-FBO)-labeled tracer. To verify this, we have produced two variants of the HER2-targeting Z(HER2:342) Affibody molecule by peptide synthesis: OA-PEP4313, where aminooxyacetic acid was conjugated directly to the N-terminal alanine, and OA-E-3-PEP4313, where a triglutamyl spacer was introduced between the aminooxy moiety and the N-terminus. We have found that the use of the spacer is associated with a minor decrease of affinity, from K-D = 49 pM to K-D = 180 pM. Radiolabeled F-18-FBO-E-3-PEP4313 demonstrated specific binding to HER2-expressing ovarian carcinoma SKOV-3 cells and slow internalization. Biodistribution studies in mice demonstrated that the use of a triglutamyl linker decreased uptake of radioactivity in liver 2.7-fold at 2 h after injection. Interestingly, radioactivity uptake in kidneys was also reduced (2.4-fold). Experiments in BALB/C nu/nu mice bearing SKOV-3 xenografts demonstrated HER2-specific uptake of F-18-FBO-E-3-PEP4313 in tumors. At 2 h pi, the tumor uptake (20 +/- 2% ID/g) exceeded uptake in liver 5-fold and uptake in kidneys 3.6-fold. The tumor-to-blood ratio was 21 +/- 3. The microPET/CT imaging experiment confirmed the biodistribution data. In conclusion, the use of a triglutamyl spacer is a convenient way to improve the biodistribution profile of Affibody molecules labeled at the N-terminus using F-18-FBA. It provides a tracer capable of producing high-contrast images of HER2-expressing tumors.
650 7a TEKNIK OCH TEKNOLOGIERx Medicinteknikx Medicinsk laboratorie- och mätteknik0 (SwePub)206012 hsv//swe
650 7a ENGINEERING AND TECHNOLOGYx Medical Engineeringx Medical Laboratory and Measurements Technologies0 (SwePub)206012 hsv//eng
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaper0 (SwePub)3012 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicine0 (SwePub)3012 hsv//eng
653 a Positron-Emission-Tomography
653 a In-Vivo
653 a Anti-Her2 Affibody
653 a Labeling Methods
653 a Her2 Expression
653 a Immuno-Pet
653 a Peptides
653 a Affinity
653 a Proteins
653 a Receptor
7001 a Thibblin, Alfu Uppsala universitet,Plattformen för preklinisk PET4 aut0 (Swepub:uu)alfthibb
7001 a Antoni, Gunnaru Uppsala universitet,Plattformen för preklinisk PET,Enheten för onkologi4 aut0 (Swepub:uu)gunnarat
7001 a Orlova, Annau Uppsala universitet,Plattformen för preklinisk PET4 aut0 (Swepub:uu)annaorlo
7001 a Eriksson Karlström, Amelieu KTH,Proteinteknologi4 aut0 (Swepub:kth)u10x6l4n
7001 a Tolmachev, Vladimiru Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Tolmachev4 aut0 (Swepub:uu)vladtolm
7001 a Honarvar, Hadisu Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Tolmachev4 aut0 (Swepub:uu)hadho340
7001 a Strand, Joannau Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Tolmachev4 aut0 (Swepub:uu)joast981
7001 a Selvaraju, Ram Kumaru Uppsala universitet,Plattformen för preklinisk PET4 aut0 (Swepub:uu)ramse695
7001 a Altai, Mohamedu Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Tolmachev4 aut0 (Swepub:uu)mohal988
7102 a KTHb Proteinteknologi4 org
7730 t Bioconjugate chemistryd : American Chemical Society (ACS)g 25:1, s. 82-92q 25:1<82-92x 1043-1802x 1520-4812
8564 u http://uu.diva-portal.org/smash/get/diva2:695994/FULLTEXT01
8564 u https://uu.diva-portal.org/smash/get/diva2:695994/FULLTEXT01.pdfx primaryx Raw objecty fulltext:preprint
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-117890
8564 8u https://doi.org/10.1021/bc400343r
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-218569

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