Aims: For the purpose of visualization and quantification of β cells, glucagon-like peptide 1 receptor (GLP-1R)-targeting imaging including single photon emission computed and positron emission tomography (SPECT/PET) has emerged recently. It is well known that internalization of the probes can affect visualization of regions of interest on SPECT/PET. However, the internalization and its effect on β-cell visualization of GLP-1R-targeting probes have not been fully examined. Therefore, we investigated time-based internalized activities of an exendin-4 (Ex4)-based probe, which was developed for clinical GLP-1R-targeting imaging.

Method: [18F]FB(ePEG12)12-Ex4 (18F-Ex4) was synthesized. Rat insulinoma cell line, INS-1 and Human Embryonic Kidney cells 293 expressing human GLP-1R (HEK_GLP-1R) were used as GLP-1R-positive cells. These cells were incubated with 18F-Ex4 (1.48 MBq) for different periods of time (0-120 minutes). Whole cell (WC) and internalized (IC) radioisotope activities were measured by the gamma counter.

Results: WC per incubated probe (IP) activities showed rapid rise within 30 minutes of incubation time and further gradual increase up to 120 minutes in INS-1 and HEK_GLP-1R cells, whereas wild type HEK293 showed no significant WC activity. The WC/IP differences between INS-1 and HEK_GLP-1R cells were significant at the 15-minutes mark (p=0.04) but reduced to insignificant after 30 minutes, although the two cell lines showed significantly different levels of GLP-1R mRNA expressions. IC/IP increased rapidly within 30 minutes and gradually up to 120 minutes. The IC/WC at the 120-minutes mark were significantly higher than those at the 30-minutes mark in both cell lines.

Conclusion: The 18F-Ex4 probe showed rapid uptakes and internalization in GLP-1R-expressing cell lines, which indicates that dual or delayed phases of GLP-1R-targeting imaging may be beneficial. In addition, a time-based hampering effect of GLP-1R-expression levels for β-cell visualization can be suggested.


T. Murakami: None. H. Fujimoto: None. N. Fujita: None. K. Hamamatsu: None. J. Fujikura: None. N. Inagaki: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Japan Tobacco Inc., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited.

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