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Pre-clinical evalua...
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Orlova, AnnaUppsala universitet,Enheten för biomedicinsk strålningsvetenskap
(author)
Pre-clinical evaluation of [111In]-benzyl-DOTA-Z(HER2:342), a potential agent for imaging of HER2 expression in malignant tumors
- Article/chapterEnglish2007
Publisher, publication year, extent ...
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Spandidos Publications,2007
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-17045
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-17045URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-16865URI
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https://doi.org/10.3892/ijmm.20.3.397DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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QC 20100525
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Imaging of expression of human epidermal growth factor receptor type 2 (HER2) in breast carcinomas may help to select patients eligible for trastuzumab therapy. The Affibody molecule Z(HER2:342) is a small (7-kDa) non-immunoglobulin affinity protein, which binds to HER2 with a picomolar affinity. Previously, a benzyl-DTPA conjugate of Z(HER2:342) was labeled with 111In and demonstrated good targeting in murine xenografts. We considered that the use of the macrocyclic chelator DOTA could increase the label stability and enhance a choice of nuclides, which could be used as a label for Z(HER2:342). The goal of this study was the preparation and pre-clinical evaluation of the indium-111- labeled DOTA-derivative of Z(HER2:342). Isothiocyanate-benzyl-DOTA was coupled to recombinant Z(HER2:342), and the conjugate was efficiently labeled with 111In at 60 degrees C. The specificity of 111In-benzyl-DOTA-Z(HER2:342) binding to HER2 was confirmed in vitro using HER2-expressing breast carcinoma BT474 and ovarian carcinoma SKOV-3 cell lines. Biodistribution of 111In-benzyl-DOTA-Z(HER2:342) was performed in nude mice bearing LS174T xenografts and compared directly with the biodistribution of 111In-benzyl-DTPA-Z(HER2:342). In vivo, 111In-benzyl-DOTA-Z(HER2:342) demonstrated quick clearance from blood and non-specific organs except the kidneys. Four hours post injection (pi), the tumor uptake of 111In-benzyl-DOTA-Z(HER2:342) (4.4+/-1.0% IA/g) was specific and the tumor-to-blood ratio was 23. The use of benzyl-DTPA provided higher tumor-to-blood and tumor-to-liver ratios. gamma-camera imaging showed clear visualization of HER2-expressing xenografts using 111In-benzyl-DOTA-Z(HER2:342). 111In-benzyl-DOTA-Z(HER2:342) has a potential for imaging of HER2 expression in malignant tumors.
Subject headings and genre
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MEDICIN OCH HÄLSOVETENSKAP Medicinsk bioteknologi hsv//swe
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MEDICAL AND HEALTH SCIENCES Medical Biotechnology hsv//eng
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Animals
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Breast Neoplasms/*genetics/metabolism/*radionuclide imaging
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Cell Line; Tumor
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Drug Evaluation; Preclinical
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Female
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Genes; erbB-2
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Humans
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Indium Radioisotopes/diagnostic use/pharmacokinetics
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Mice
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Mice; Inbred BALB C
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Mice; Nude
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Neoplasm Transplantation
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Ovarian Neoplasms/*genetics/metabolism/*radionuclide imaging
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Pentetic Acid/*analogs & derivatives/diagnostic use/pharmacokinetics
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Radiopharmaceuticals/diagnostic use/pharmacokinetics
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Receptor; erbB-2/metabolism
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Tissue Distribution
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Transplantation; Heterologous
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MEDICINE
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MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
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Tran, ThuyUppsala universitet,Enheten för biomedicinsk strålningsvetenskap(Swepub:uu)thutr111
(author)
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Widström, CharlesUppsala universitet,Avdelningen för sjukhusfysik
(author)
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Engfeldt, Torun
(author)
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Eriksson Karlström, AmelieKTH,Molekylär Bioteknologi(Swepub:kth)u10x6l4n
(author)
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Tolmachev, VladimirUppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Institutionen för medicinska vetenskaper(Swepub:uu)vladtolm
(author)
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Uppsala universitetEnheten för biomedicinsk strålningsvetenskap
(creator_code:org_t)
Related titles
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In:International Journal of Molecular Medicine: Spandidos Publications20:3, s. 397-4041107-37561791-244X
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