TY - JOUR T1 - Human Epidermal Growth Factor Receptor 3–Specific Tumor Uptake and Biodistribution of <sup>89</sup>Zr-MSB0010853 Visualized by Real-Time and Noninvasive PET Imaging JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1210 LP - 1215 DO - 10.2967/jnumed.116.181586 VL - 58 IS - 8 AU - Frank J. Warnders AU - Anton G.T. Terwisscha van Scheltinga AU - Christine Knuehl AU - Maarten van Roy AU - Erik F.J. de Vries AU - Jos G.W. Kosterink AU - Elisabeth G.E. de Vries AU - Marjolijn N. Lub-de Hooge Y1 - 2017/08/01 UR - http://jnm.snmjournals.org/content/58/8/1210.abstract N2 - The human epidermal growth factor receptor 3 (HER3) is an interesting target for antitumor therapy. For optimal HER3 signaling inhibition, a biparatopic Nanobody construct (MSB0010853) was developed that binds 2 different HER3 epitopes. In addition, MSB0010853 contains a third HER3 epitope that binds albumin to extend its circulation time. MSB0010853 is cross-reactive with HER3 and albumin of mouse origin. We aimed to gain insight into MSB0010853 biodistribution and tumor uptake by radiolabeling the Nanobody construct with 89Zr. Methods: MSB0010853 was radiolabeled with 89Zr. Dose- and time-dependent tumor uptake was studied in nude BALB/c mice bearing a subcutaneous HER3 overexpressing H441 non–small cell lung cancer xenograft. Dose-dependent biodistribution of 89Zr-MSB0010853 was assessed ex vivo at 24 h after intravenous injection. Protein doses of 5, 10, 25, 100, and 1,000 μg were used. Time-dependent biodistribution of MSB0010853 was analyzed ex vivo at 3, 6, 24, and 96 h after intravenous administration of 25 μg of 89Zr-MSB0010853. PET imaging and biodistribution were performed 24 h after administration of 25 μg of 89Zr-MSB0010853 to mice bearing human H441, FaDu (high HER3 expression), or Calu-1 (no HER3 expression) tumor xenografts. Results: Radiolabeling of MSB0010853 with 89Zr was performed with a radiochemical purity of greater than 95%. Ex vivo biodistribution showed protein dose– and time-dependent distribution of 89Zr-MSB0010853 in all organs. Uptake of 89Zr-MSB0010853 in H441 tumors was only time-dependent. Tumor could be visualized up to at least 96 h after injection. The highest mean SUV of 0.6 ± 0.2 was observed at 24 h after injection of 25 μg of 89Zr-MSB0010853. 89Zr-MSB0010853 tumor uptake correlated with HER3 expression and was highest in H441 (6.2 ± 1.1 percentage injected dose per gram [%ID/g]) and lowest in Calu-1 (2.3 ± 0.3 %ID/g) xenografts. Conclusion: 89Zr-MSB0010853 organ distribution and tumor uptake in mice are time-dependent, and tumor uptake correlates with HER3 expression. In contrast to tumor uptake except for kidney uptake, organ distribution of 89Zr-MSB0010853 is protein dose–dependent for the tested doses. 89Zr-MSB0010853 PET imaging gives insight into the in vivo behavior of MSB0010853. ER -