TY - JOUR T1 - Radiolabeled-DOTA-Exendin-3, a new agent for the detection of insulinomas with PET or SPECT JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1568 LP - 1568 VL - 50 IS - supplement 2 AU - Maarten Brom AU - Wim Oyen AU - Lieke Joosten AU - M. Gotthardt AU - Otto Boerman Y1 - 2009/05/01 UR - http://jnm.snmjournals.org/content/50/supplement_2/1568.abstract N2 - 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® 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 ± 7.2 %ID/g. Uptake was specific as determined by co-injection of an excess of unlabeled Exendin-3 (1.2 ± 0.03 %ID/g). The pancreas also exhibited high and specific uptake: 11.3 ± 1.0 %ID/g. Uptake in the kidneys was very high: 144 ± 24 %ID/g and was not receptor-mediated (145 ± 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 ± 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 ER -