Abstract | PURPOSE: METHODS: Affinity and binding properties of [125I] SFITGv6 or [177Lu] SFITGv6 for αvβ6 integrin-expressing NSCLC cell lines were evaluated in cell culture experiments including competition, kinetic, internalization, and efflux. To confirm αvβ6 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. RESULTS: In vitro experiments revealed a significant time-dependent SFITGv6 binding of up to 33 % to αvβ6 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 [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 SUVmax values in histologically proven NSCLC lesions, but a generally higher accumulation of [18F] FDG was noticed. CONCLUSIONS: Even if SFITGv6 demonstrates excellent affinity and specificity for αvβ6 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.
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Authors | Paul Flechsig, Thomas Lindner, Anastasia Loktev, Saskia Roesch, Walter Mier, Max Sauter, Michael Meister, Christel Herold-Mende, Uwe Haberkorn, Annette Altmann |
Journal | Molecular imaging and biology
(Mol Imaging Biol)
Vol. 21
Issue 5
Pg. 973-983
(10 2019)
ISSN: 1860-2002 [Electronic] United States |
PMID | 30671741
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Neoplasm
- Gallium Radioisotopes
- Integrins
- Peptide Fragments
- SFITGv6 peptide
- integrin alphavbeta6
- Fluorodeoxyglucose F18
- Gallium-68
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Topics |
- Animals
- Antigens, Neoplasm
(metabolism)
- Carcinoma, Non-Small-Cell Lung
(diagnostic imaging)
- Cell Line, Tumor
- Fluorodeoxyglucose F18
- Gallium Radioisotopes
(chemistry)
- Humans
- Integrins
(metabolism)
- Lung Neoplasms
(diagnostic imaging)
- Mice, Inbred BALB C
- Mice, Nude
- Peptide Fragments
(metabolism)
- Positron Emission Tomography Computed Tomography
- Tissue Distribution
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