PET/CT Imaging of NSCLC with a α_vβ₆ Integrin-Targeting Peptide

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 α_vβ₆ integrin-specific peptide SFITGv6 as a diagnostic reagent targeting NSCLC.

Affinity and binding properties of [¹²⁵I]SFITGv6 or [¹⁷⁷Lu]SFITGv6 for α_vβ₆ integrin-expressing NSCLC cell lines were evaluated in cell culture experiments including competition, kinetic, internalization, and efflux. To confirm α_vβ₆ integrin specificity in vivo small-animal positron emission tomography (PET) imaging using [⁶⁸Ga]SFITGv6 as radiotracer and biodistribution of [¹⁷⁷Lu]SFITGv6 in NCI-H2009 and NCI-H322 tumor-bearing mice was performed. Finally, to distinguish between benign and malignant lesions [⁶⁸Ga]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-[¹⁸F]flouro-D-glucose ([¹⁸F]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.

In vitro experiments revealed a significant time-dependent SFITGv6 binding of up to 33 % to α_vβ₆ integrin-expressing the cell lines NCI-H2009, NCI-H322, NCI-H292, NCI-H358, and high affinity (IC_50-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 [¹⁸F] FDG injection followed by [⁶⁸Ga]SFITGv6 application revealed correlating images. Comparing the uptake of [⁶⁸Ga]SFITGv6 and [¹⁸F] FDG both PET/CT-examinations presented with significantly increased SUV_max values in histologically proven NSCLC lesions, but a generally higher accumulation of [¹⁸F] FDG was noticed.

Even if SFITGv6 demonstrates excellent affinity and specificity for α_vβ₆ integrin-expressing NSCLC cell lines and several NSCLC xenografts [¹⁸F]FDG-PET/CT provides an advantage over [⁶⁸Ga]SFITGv6-PET/CT for the diagnosis of NSCLC patients.