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LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004981naa a2200493 4500
001oai:DiVA.org:uu-17054
003SwePub
008090325s2008 | |||||||||||000 ||eng|
009oai:DiVA.org:kth-9724
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-170542 URI
0247 a https://doi.org/10.1007/s00259-008-0845-72 DOI
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-97242 URI
040 a (SwePub)uud (SwePub)kth
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Ekblad, Torunu KTH,Skolan för bioteknologi (BIO)4 aut0 (Swepub:kth)u18tluq7
2451 0a Development and preclinical characterisation of 99mTc-labelled Affibody molecules with reduced renal uptake
264 c 2008-07-02
264 1b Springer Science and Business Media LLC,c 2008
338 a print2 rdacarrier
500 a QC 20100716. Uppdaterad från in press till published (20100716).
520 a Purpose  Affibody molecules are low molecular weight proteins (7 kDa), which can be selected to bind to tumour-associated target proteins with subnanomolar affinity. Because of rapid tumour localisation and clearance from nonspecific compartments, Affibody molecules are promising tracers for molecular imaging. Earlier, 99mTc-labelled Affibody molecules demonstrated specific targeting of tumour xenografts. However, the biodistribution was suboptimal either because of hepatobiliary excretion or high renal uptake of the radioactivity. The goal of this study was to optimise the biodistribution of Affibody molecules by chelator engineering. Materials and methods  Anti-HER2 ZHER2:342 Affibody molecules, carrying the mercaptoacetyl-glutamyl-seryl-glutamyl (maESE), mercaptoacetyl-glutamyl-glutamyl-seryl (maEES) and mercaptoacetyl-seryl-glutamyl-glutamyl (maSEE) chelators, were prepared by peptide synthesis and labelled with 99mTc. The tumour-targeting capacity of these conjugates was compared with each other and with the best previously available conjugate, 99mTc-maEEE-ZHER2:342, in nude mice bearing SKOV-3 xenografts. The tumour-targeting capacity of the most promising conjugate, 99mTc-maESE-ZHER2:342, was compared with radioiodinated ZHER2:342. Results  All novel conjugates demonstrated successful tumour targeting and a low degree of hepatobiliary excretion. The renal uptakes of serine-containing conjugates, 33 ± 5, 68 ± 21 and 71 ± 10%IA/g, for99mTc-maESE-ZHER2:342, 99mTc-maEES-ZHER2:342 and 99mTc-maSEE-ZHER2:342, respectively, were significantly reduced in comparison with 99mTc-maEEE-ZHER2:342 (102 ± 13%IA/g). For 99mTc-maESE-ZHER2:342, a tumour uptake of 9.6 ± 1.8%IA/g and a tumour-to-blood ratio of 58 ± 6 were reached at 4 h p.i. Conclusions  A combination of serine and glutamic acid residues in the chelator sequence confers increased renal excretion and relatively low renal uptake of 99mTc-labelled Affibody molecules. In combination with preserved targeting capacity, this improved imaging of targets in abdominal area.
653 a Affibody molecule
653 a HER2
653 a Renal uptake
653 a Technetium-99m
653 a Tumour targeting
653 a MEDICINE
653 a MEDICIN
7001 a Tran, Thuyu Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University4 aut
7001 a Orlova, Annau Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University4 aut0 (Swepub:uu)annaorlo
7001 a Widström, Charlesu Uppsala universitet,Enheten för onkologi,Section of Hospital Physics, Department of Oncology, Uppsala University Hospital4 aut
7001 a Feldwisch, Joachimu Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University4 aut
7001 a Abrahmsén, Larsu Affibody AB, Bromma4 aut
7001 a Wennborg, Andersu Affibody AB, Bromma4 aut
7001 a Eriksson Karlström, Amelieu KTH,Skolan för bioteknologi (BIO)4 aut0 (Swepub:kth)u10x6l4n
7001 a Tolmachev, Vladimiru Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,Institutionen för medicinska vetenskaper,Unit of Nuclear Medicine, Department of Medical Sciences, Uppsala University4 aut0 (Swepub:uu)vladtolm
7102 a KTHb Skolan för bioteknologi (BIO)4 org
7730 t European Journal of Nuclear Medicine and Molecular Imagingd : Springer Science and Business Media LLCg 35:12, s. 2245-2255q 35:12<2245-2255x 1619-7070x 1619-7089
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-17054
8564 8u https://doi.org/10.1007/s00259-008-0845-7
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-9724

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