TY - JOUR T1 - <strong>Targeted molecular imaging of c-Met in NSCLC using <sup>68</sup>Ga-labeled binding peptide</strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1042 LP - 1042 VL - 60 IS - supplement 1 AU - Xilin Sun AU - Zhaoguo Han AU - Ji Yan AU - Yang Liu AU - CHANGJIU ZHAO AU - Kai Wang Y1 - 2019/05/01 UR - http://jnm.snmjournals.org/content/60/supplement_1/1042.abstract N2 - 1042Objectives: c-Met is a receptor tyrosine kinase, implicating cellular processes including proliferation and apoptosis [1]. Abnormal activation of c-Met pathway plays important role in tumorigenesis, progressionin NSCLC andmediates acquired resistance to epidermal growth factor receptor (EGFR) targeted therapy in NSCLC [2]. Nevertheless, lacking accurate in vivo detection methods for c-Metchallenges the understanding of the underlying c-Met related EGFR-TKI resistance mechanismand overall efficacy of c-Met targeted treatment. In this study, we developed a novel PET tracer (68Ga-NODAGA-cMBP) based on c-Met-specific peptide with favorable pharmacokinetics and smaller size (~2 kDa) than antibodies (~150 kDa) and successfully used to image c-Met in NSCLC. Methods: cMBP (KSLSRHDHIHHH)is a c-Met-specific peptideidentified from phage display library [3], here, we synthesized and modified cMBP with a linker-NODAGA and purified with HPLC. Then 10 ug of NODAGA-cMBPwas added into 68GaCl3 (536.5 MBq in 1 mL) for chelation reaction. Stability of 68Ga-NODAGA-cMBP in phosphate buffer was measured by radio-HPLCin incubation time of 0.5, 1, 2, 4 h. Subcutaneous transplanted human NSCLC xenograftswith overexpression of c-Met (H1993) were established to assess tracer efficiencyand normal physiological level of c-Met (H1299) as negative control groups. PET/CT scanning (Discovery790Elite, GE healthcare) was performed at 0.5 h, 1 h and 2h after tail vein injection of 68Ga-NODAGA-cMBP (9.25 MBq in 150 uL saline,n=3). Image quantification was performed at AW4.6 software (GE Healthcare) with decay-corrected and calculated as %ID/g. Cell uptake and biodistribution of 68Ga-NODAGA-cMBP will be further supplemented. Results: 68Ga-NODAGA-cMBP was prepared with labeling yield of ≥62%and radiochemical purity of ≥95%. Stability of 68Ga-NODAGA-cMBPin phosphate buffer was expressed as radiochemical purity and always &gt;95% in all incubation time.H1993 tumors could be clearly observed in PET images (figure 1) at early 0.5 h after injection with highest tumor uptake of 0.77±0.04 %ID/g, significantly higher than H1299 (0.38±0.06 %ID/g, P &lt; 0.01). At 1 h and 2 h, tumor uptake was gradually decreased, but H1299 tumors were always obviously lower than H1993 tumors (P &lt; 0.05). From sequential images, we also find that 68Ga-NODAGA-cMBP can accumulate in c-Met-positive tumors quickly and specificly and be cleared through urinary system rapidly. As we know, imaging agents with rapid metabolism matching short half-life nuclide could provide favorable pharmacokinetics, and so did 68Ga-NODAGA-cMBP (t1/2=68.1 min).Conclution: We successfully develop a novel 68Ga-NODAGA-cMBPradiotracer with specific for c-Met and in vivoresults indicated 68Ga-NODAGA-cMBPwas feasible to quantitatively detect c-Met in NSCLC by PET/CT imaging.The 68Ga-NODAGA-cMBPPET/CT imaging has potential to be used for understanding the c-Met related tumorigenesis, progression and EGFR-TKI resistance mechanismin the noninvasive way. REFERENCES: 1 Trusolino L, Bertotti A, Comoglio PM. MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol. 2010;11:834-848.2 Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 2007;316:1039-1043.3 Kim K, Hur Y, Ryu EK, et al. A neutralizable epitope is induced on HGF upon its interaction with its receptor cMet. Biochem Biophys Res Commun. 2007;354:115-121. ER -