RT Journal Article SR Electronic T1 HER2-Positive Tumors Imaged Within 1 Hour Using a Site-Specifically 11C-Labeled Sel-Tagged Affibody Molecule JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.111.102194 DO 10.2967/jnumed.111.102194 A1 Wållberg, Helena A1 Grafström, Jonas A1 Cheng, Qing A1 Lu, Li A1 Martinsson Ahlzén, Hanna-Stina A1 Samén, Erik A1 Thorell, Jan-Olov A1 Johansson, Katarina A1 Dunås, Finn A1 Olofsson, Maria Hägg A1 Stone-Elander, Sharon A1 Arnér, Elias S.J. A1 Ståhl, Stefan YR 2012 UL http://jnm.snmjournals.org/content/early/2012/08/07/jnumed.111.102194.abstract AB 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, ZHER2:342, was recombinantly fused with a C-terminal selenocysteine-containing tetrapeptide Sel-tag, allowing site-specific labeling with either 11C or 68Ga, 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 11C-labeled Affibody molecule. Results: Both the 11C- and 68Ga-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 11C-labeled protein, and its overall absorbed dose was considerably lower. 11C-ZHER2:342 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 11C-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, 11C-labeled Sel-tagged ZHER2:342 can successfully be used for rapid and repeated PET studies of HER2 expression in tumors.