[68Ga]Ga-DO3A-VS-Cys40-Exendin-4 was evaluated for binding to GLP-1R by in vitro autoradiography binding studies in INS-1 tumor from xenografts. In vivo biodistribution was investigated in healthy control mice, INS-1 xenografted and PANC1 xenografted immunodeficient mice at two different doses of peptide: 2.5 渭g/kg (baseline) and 100 渭g/kg (block). In vivo imaging of [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 in xenografted mice was evaluated by small animal PET/CT using a direct comparison with the clinically established insulinoma marker [11C]5-hydroxy-tryptophan ([11C]5-HTP).
GLP-1 receptor density could be quantified in INS-1 tumor biopsies. [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 showed significant uptake (p ≤ 0.05) in GLP1-R positive tissues such as INS-1 tumor, lungs and pancreas upon comparison between baseline and blocking studies. In vivo imaging showed concordant results with higher tumor-to-muscle ratio in INS-1 xenografted mice compared with [11C]5-HTP.
[68Ga]Ga-DO3A-VS-Cys40-Exendin-4 has high affinity and specificity for GLP-1R expressed on insulinoma in vitro and in vivo.