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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 ...
- Spandidos Publications,2007
- printrdacarrier
Numbers
- LIBRIS-ID:oai:DiVA.org:uu-17045
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-17045URI
- https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-16865URI
- https://doi.org/10.3892/ijmm.20.3.397DOI
Supplementary language notes
- Language:English
- Summary in:English
Part of subdatabase
- SwePubSwePub
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Notes
- QC 20100525
- 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
- MEDICIN OCH HÄLSOVETENSKAP Medicinsk bioteknologi hsv//swe
- MEDICAL AND HEALTH SCIENCES Medical Biotechnology hsv//eng
- Animals
- Breast Neoplasms/*genetics/metabolism/*radionuclide imaging
- Cell Line; Tumor
- Drug Evaluation; Preclinical
- Female
- Genes; erbB-2
- Humans
- Indium Radioisotopes/diagnostic use/pharmacokinetics
- Mice
- Mice; Inbred BALB C
- Mice; Nude
- Neoplasm Transplantation
- Ovarian Neoplasms/*genetics/metabolism/*radionuclide imaging
- Pentetic Acid/*analogs & derivatives/diagnostic use/pharmacokinetics
- Radiopharmaceuticals/diagnostic use/pharmacokinetics
- Receptor; erbB-2/metabolism
- Tissue Distribution
- Transplantation; Heterologous
- MEDICINE
- MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
- Tran, ThuyUppsala universitet,Enheten för biomedicinsk strålningsvetenskap(Swepub:uu)thutr111 (author)
- Widström, CharlesUppsala universitet,Avdelningen för sjukhusfysik (author)
- Engfeldt, Torun (author)
- Eriksson Karlström, AmelieKTH,Molekylär Bioteknologi(Swepub:kth)u10x6l4n (author)
- Tolmachev, VladimirUppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Institutionen för medicinska vetenskaper(Swepub:uu)vladtolm (author)
- Uppsala universitetEnheten för biomedicinsk strålningsvetenskap (creator_code:org_t)
Related titles
- In:International Journal of Molecular Medicine: Spandidos Publications20:3, s. 397-4041107-37561791-244X
Internet link
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=17671747&dopt=Citation
- https://www.spandidos-publications.com/ijmm/20/3/397/download
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-17045
- https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-16865
- https://doi.org/10.3892/ijmm.20.3.397
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