TY - JOUR T1 - In Vivo Visualization of MET Tumor Expression and Anticalin Biodistribution with the MET-Specific Anticalin <sup>89</sup>Zr-PRS-110 PET Tracer JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 665 LP - 671 DO - 10.2967/jnumed.113.124941 VL - 55 IS - 4 AU - Anton G.T. Terwisscha van Scheltinga AU - Marjolijn N. Lub-de Hooge AU - Marlon J. Hinner AU - Remy B. Verheijen AU - Andrea Allersdorfer AU - Martin Hülsmeyer AU - Wouter B. Nagengast AU - Carolien P. Schröder AU - Jos G.W. Kosterink AU - Elisabeth G.E. de Vries AU - Laurent Audoly AU - Shane A. Olwill Y1 - 2014/04/01 UR - http://jnm.snmjournals.org/content/55/4/665.abstract N2 - Anticalins are a novel class of biopharmaceuticals, displaying highly desirable attributes as imaging agents. The anticalin PRS-110 was rationally engineered to target the oncogene MET with high affinity and specificity. The aim of this study was to visualize MET expression and analyze biodistribution of 89Zr-labeled PRS-110 in human tumor–bearing mice. Methods: 89Zr-PRS-110 was generated. For biodistribution studies (96 h after injection of tracer) 10 μg of 89Zr-PRS-110 (with 0–490 μg of unlabeled PRS-110) were injected into BALB/c mice bearing high MET-expressing H441 non–small cell lung cancer xenografts. Further characterization with PET imaging was performed at 6, 24, 48, and 96 h after injection of 50 μg of 89Zr-PRS-110 into mice bearing H441, primary glioblastoma U87-MG (intermediate MET), or ovarian cancer A2780 (low MET) xenografts. Drug distribution was also analyzed ex vivo using fluorescently labeled PRS-110. Results: Biodistribution analyses showed a dose-dependent tumor uptake of 89Zr-PRS-110, with the highest fractional tumor uptake at 10 μg of 89Zr-PRS-110, with no unlabeled PRS-110. Small-animal PET imaging supported by biodistribution data revealed specific tumor uptake of 89Zr-PRS-110 in the MET-expressing H441 and U87-MG tumors whereas the MET-negative A2780 tumor model showed a lower uptake similar to a non-MET binder anticalin control. Tumor uptake increased up to 24 h after tracer injection and remained high, whereas uptake in other organs decreased over time. Ex vivo fluorescence revealed intracellular presence of PRS-110. Conclusion: 89Zr-PRS-110 specifically accumulates in MET-expressing tumors in a receptor density–dependent manner. PET imaging provides real-time noninvasive information about PRS-110 distribution and tumor accumulation in preclinical models. ER -