@article {Brom1568, author = {Maarten Brom and Wim Oyen and Lieke Joosten and M. Gotthardt and Otto Boerman}, title = {Radiolabeled-DOTA-Exendin-3, a new agent for the detection of insulinomas with PET or SPECT}, volume = {50}, number = {supplement 2}, pages = {1568--1568}, year = {2009}, publisher = {Society of Nuclear Medicine}, abstract = {1568 Objectives Insulinomas are neuroendrocrine tumors derived from malignant pancreatic β-cells. The GLP-1 receptor (GLP-1R) is expressed at a high incidence (\>90\%) and high density in insulinomas. GLP-1, the natural ligand of the GLP-1R, is rapidly degraded in vivo. A more stable agonist of GLP-1 is Exendin-3. We investigated imaging of insulinomas with DOTA-conjugated Exendin-3 labeled with 111In or 68Ga. Methods Targeting of insulinomas with DOTA-Exendin-3 labeled with either 111In or 68Ga was investigated in vitro using insulinoma tumor cells (INS). In vivo targeting was investigated in BALB/c nude mice with subcutaneous (s.c.) INS tumors. PET imaging was performed using an Inveon{\textregistered} preclinical PET/CT scanner. Results In vitro assays showed specific binding and internalization of Exendin-3. In BALB/c nude mice with s.c. INS tumors a remarkably high uptake of 111In-DOTA-Exendin-3 in the tumor was observed : 25.4 {\textpm} 7.2 \%ID/g. Uptake was specific as determined by co-injection of an excess of unlabeled Exendin-3 (1.2 {\textpm} 0.03 \%ID/g). The pancreas also exhibited high and specific uptake: 11.3 {\textpm} 1.0 \%ID/g. Uptake in the kidneys was very high: 144 {\textpm} 24 \%ID/g and was not receptor-mediated (145 {\textpm} 3.5 \%ID/g). The biodistribution of 68Ga-labelled DOTA-Exendin-3 was similar to that of 111In-labelled DOTA-Exendin-3, although tumor uptake was significantly lower (8.9 {\textpm} 3.1 \%ID/g). The subcutaneous tumors were clearly visualized by small animal PET imaging after injection of 5 MBq of 68Ga-DOTA-Exendin-3. Conclusions 111In-DOTA-Exendin-3 and 68Ga-DOTA-Exendin-3 specifically accumulate in insulinomas. Therefore, 111In- DOTA-Exendin-3 and 68Ga-DOTA-Exendin-3 are promising tracers to visualize insulinoma lesions with PET and SPECT}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/50/supplement_2/1568}, eprint = {https://jnm.snmjournals.org/content}, journal = {Journal of Nuclear Medicine} }