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Pre-clinical evalua...
Pre-clinical evaluation of [111In]-benzyl-DOTA-Z(HER2:342), a potential agent for imaging of HER2 expression in malignant tumors
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- Orlova, Anna (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Tran, Thuy (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap
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- Widström, Charles (författare)
- Uppsala universitet,Avdelningen för sjukhusfysik
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Engfeldt, Torun (författare)
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- Eriksson Karlström, Amelie (författare)
- KTH,Molekylär Bioteknologi
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- Tolmachev, Vladimir (författare)
- Uppsala universitet,Enheten för biomedicinsk strålningsvetenskap,Institutionen för medicinska vetenskaper
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(creator_code:org_t)
- Spandidos Publications, 2007
- 2007
- Engelska.
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Ingår i: International Journal of Molecular Medicine. - : Spandidos Publications. - 1107-3756 .- 1791-244X. ; 20:3, s. 397-404
- Relaterad länk:
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http://www.ncbi.nlm....
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https://www.spandido...
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https://urn.kb.se/re...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology (hsv//eng)
Nyckelord
- 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
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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