Search: WFRF:(Stone Elander Sharon)
> (2010-2014) >
HER2-Positive Tumor...
HER2-Positive Tumors Imaged Within 1 Hour Using a Site-Specifically C-11-Labeled Sel-Tagged Affibody Molecule
-
- Wållberg, Helena (author)
- KTH,Molekylär Bioteknologi
-
- Grafström, Jonas (author)
- Karolinska Institutet
-
- Cheng, Qing (author)
- Karolinska Institutet
-
show more...
-
Lu, Li (author)
-
Ahlzén, Hanna-Stina Martinsson (author)
-
- Samén, Erik (author)
- Karolinska Institutet
-
Thorell, Jan-Olov (author)
-
- Johansson, Katarina (author)
- Karolinska Institutet
-
Dunås, Finn (author)
-
- Olofsson, Maria Hägg (author)
- Karolinska Institutet
-
- Stone-Elander, Sharon (author)
- Karolinska Institutet
-
Arnér, Elias S. J. (author)
-
- Ståhl, Stefan (author)
- KTH,Molekylär Bioteknologi
-
show less...
-
(creator_code:org_t)
-
-
show more...
-
-
show less...
- ISSN 1535-5667
- 2012-08-07
- 2012
- English.
-
In: Journal of Nuclear Medicine. - Stockholm : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 53:9, s. 1446-1453
- Related links:
-
http://jnm.snmjourna...
-
show more...
-
http://hdl.handle.ne... (primary) (Object in context) (free)
-
https://urn.kb.se/re...
-
https://doi.org/10.2...
-
http://hdl.handle.ne...
-
http://kipublication...
-
show less...
Abstract
Subject headings
Close
- A rapid, reliable method for distinguishing tumors or metastases that overexpress human epidermal growth factor receptor 2 (HER2) from those that do not is highly desired for individualizing therapy and predicting prognoses. In vivo imaging methods are available but not yet in clinical practice; new methodologies improving speed, sensitivity, and specificity are required. Methods: A HER2-binding Affibody molecule, Z(HER2:342), was recombinantly fused with a C-terminal selenocysteine-containing tetrapeptide Sel-tag, allowing site-specific labeling with either C-11 or Ga-68, followed by biodistribution studies with small-animal PET. Dosimetry data for the 2 radiotracers were compared. Imaging of HER2-expressing human tumor xenografts was performed using the C-11-labeled Affibody molecule. Results: Both the C-11- and Ga-68-labeled tracers initially cleared rapidly from the blood, followed by a slower decrease to 4-5 percentage injected dose per gram of tissue at 1 h. Final retention in the kidneys was much lower (>5-fold) for the C-11-labeled protein, and its overall absorbed dose was considerably lower. C-11-Z(HER2:342) showed excellent tumor-targeting capability, with almost 10 percentage injected dose per gram of tissue in HER2-expressing tumors within 1 h. Specificity was demonstrated by preblocking binding sites with excess ligand, yielding significantly reduced radiotracer uptake (P = 0.002), comparable to uptake in tumors with low HER2 expression. Conclusion: To our knowledge, the Sel-tagging technique is the first that enables site-specific C-11-radiolabeling of proteins. Here we present the finding that, in a favorable combination between radionuclide half-life and in vivo pharmacokinetics of the Affibody molecules, C-11-labeled Set-tagged Z(HER2:342) can successfully be used for rapid and repeated PET studies of HER2 expression in tumors.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- Affibody molecule
- Sel-tag
- C-11
- selenium
- positron emission tomography
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Wållberg, Helena
-
Grafström, Jonas
-
Cheng, Qing
-
Lu, Li
-
Ahlzén, Hanna-St ...
-
Samén, Erik
-
show more...
-
Thorell, Jan-Olo ...
-
Johansson, Katar ...
-
Dunås, Finn
-
Olofsson, Maria ...
-
Stone-Elander, S ...
-
Arnér, Elias S. ...
-
Ståhl, Stefan
-
show less...
- About the subject
-
- NATURAL SCIENCES
-
NATURAL SCIENCES
-
and Biological Scien ...
-
and Biochemistry and ...
- Articles in the publication
-
Journal of Nucle ...
- By the university
-
Royal Institute of Technology
-
Karolinska Institutet