PET/CT Imaging of NSCLC with a αvβ6 Integrin-Targeting Peptide

Purpose Targeted therapies are regarded as promising approaches to increase 5-year survival rate of non-small cell lung cancer (NSCLC) patients. Here, we investigated the clinical value of the alpha(v)beta(6) integrin-specific peptide SFITGv6 as a diagnostic reagent targeting NSCLC. Methods Affinity and binding properties of [I-125]SFITGv6 or [Lu-177]SFITGv6 for alpha(v)beta(6) integrin-expressing NSCLC cell lines were evaluated in cell culture experiments including competition, kinetic, internalization, and efflux. To confirm alpha(v)beta(6) integrin specificity in vivo small-animal positron emission tomography (PET) imaging using [Ga-68]SFITGv6 as radiotracer and biodistribution of [Lu-177]SFITGv6 in NCI-H2009 and NCI-H322 tumor-bearing mice was performed. Finally, to distinguish between benign and malignant lesions [Ga-68]SFITGv6 was applied as radiotracer for PET/x-ray computed tomography (CT) imaging of NSCLC patients with unclear diagnosis upon routinely performed 2-deoxy-2-[F-18]flouro-D-glucose ([F-18]FDG)-PET/CT. The biodistribution of the SFITGv6-ligand in different organs and tumor lesions of NSCLC patients was quantified 1 h and 3 h after injection measuring standard uptake values (SUV)(max). Results In vitro experiments revealed a significant time-dependent SFITGv6 binding of up to 33 % to alpha(v)beta(6) integrin-expressing the cell lines NCI-H2009, NCI-H322, NCI-H292, NCI-H358, and high affinity (IC50-mean 3.1 nM) to NCI-H2009 and NCI-H322. Moreover, a fast internalization of approximately 66 % by NCI-H2009 and NCI-H322 cells was observed. Small-animal PET imaging and biodistribution experiments of NCI-H2009 and NCI-H322 xenografts demonstrated an increased tumor-specific accumulation of SFITGv6 40 to 60 min after injection. Finally, PET/CT scans of NSCLC patients after [F-18] FDG injection followed by [Ga-68]SFITGv6 application revealed correlating images. Comparing the uptake of [Ga-68]SFITGv6 and [F-18] FDG both PET/CT-examinations presented with significantly increased SUVmax values in histologically proven NSCLC lesions, but a generally higher accumulation of [F-18] FDG was noticed. Conclusions Even if SFITGv6 demonstrates excellent affinity and specificity for alpha(v)beta(6) integrin-expressing NSCLC cell lines and several NSCLC xenografts [F-18]FDG-PET/CT provides an advantage over [Ga-68]SFITGv6-PET/CT for the diagnosis of NSCLC patients.