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HER2-Positive Tumors Imaged Within 1 Hour Using a Site-Specifically C-11-Labeled Sel-Tagged Affibody Molecule
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- Wållberg, Helena (författare)
- KTH,Molekylär Bioteknologi
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- Grafström, Jonas (författare)
- Karolinska Institutet
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- Cheng, Qing (författare)
- Karolinska Institutet
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Lu, Li (författare)
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Ahlzén, Hanna-Stina Martinsson (författare)
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- Samén, Erik (författare)
- Karolinska Institutet
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Thorell, Jan-Olov (författare)
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- Johansson, Katarina (författare)
- Karolinska Institutet
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Dunås, Finn (författare)
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- Olofsson, Maria Hägg (författare)
- Karolinska Institutet
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- Stone-Elander, Sharon (författare)
- Karolinska Institutet
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Arnér, Elias S. J. (författare)
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- Ståhl, Stefan (författare)
- KTH,Molekylär Bioteknologi
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- ISSN 1535-5667
- 2012-08-07
- 2012
- Engelska.
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Ingår i: Journal of Nuclear Medicine. - Stockholm : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 53:9, s. 1446-1453
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Affibody molecule
- Sel-tag
- C-11
- selenium
- positron emission tomography
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- art (ämneskategori)
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Wållberg, Helena
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Grafström, Jonas
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Cheng, Qing
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Lu, Li
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Ahlzén, Hanna-St ...
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Samén, Erik
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visa fler...
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Thorell, Jan-Olo ...
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Johansson, Katar ...
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Dunås, Finn
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Olofsson, Maria ...
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Stone-Elander, S ...
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Arnér, Elias S. ...
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Ståhl, Stefan
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visa färre...
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