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HER2-Positive Tumors Imaged Within 1 Hour Using a Site-Specifically C-11-Labeled Sel-Tagged Affibody Molecule
KTH, Skolan för bioteknologi (BIO), Molekylär Bioteknologi.
Vise andre og tillknytning
2012 (engelsk)Inngår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 53, nr 9, s. 1446-1453Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
2012. Vol. 53, nr 9, s. 1446-1453
Emneord [en]
Affibody molecule, Sel-tag, C-11, selenium, positron emission tomography
HSV kategori
Identifikatorer
URN: urn:nbn:se:kth:diva-104146DOI: 10.2967/jnumed.111.102194ISI: 000308685100029Scopus ID: 2-s2.0-84866162512OAI: oai:DiVA.org:kth-104146DiVA, id: diva2:563685
Forskningsfinansiär
Swedish Research Council, 40510402 2004-5104 2008-2654 2008-3186
Merknad

QC 20121031

Tilgjengelig fra: 2012-10-31 Laget: 2012-10-29 Sist oppdatert: 2017-12-07bibliografisk kontrollert

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