Glucagon-like peptide-1 receptor imaging for localization of insulinomas.
BACKGROUND
The surgical removal of insulinomas is hampered by difficulties to localize it using conventional radiological procedures. Recently these tumors were shown to exhibit a very high density of glucagon-like peptide-1 receptors (GLP-1R) in vitro that may be used as specific targets for in vivo receptor radiolabeling.


OBJECTIVE
The objective of the study was to test the 111In-labeled GLP-1R agonist 111In-DOTA-exendin-4 in localizing insulinomas using single photon emission computed tomography in combination with computed tomography images.


METHODS
This was a prospective open-label investigation.


METHODS
The study was conducted at three tertiary referral centers in Switzerland.


METHODS
Patients included six consecutive patients with proven clinical and biochemical endogenous hyperinsulinemic hypoglycemia.


METHODS
(111)In-DOTA-exendin-4 was administered iv at a dose of about 90 MBq (30 microg peptide) over 5 min. Whole-body planar images of the abdomen were performed at 20 min, 4 h, 23 h, 96 h, and up to 168 h after injection. After surgical removal of the insulinomas, GLP-1R expression was assessed in the tumor tissue in vitro by GLP-1R autoradiography.


METHODS
The detection rate of insulinomas was measured.


RESULTS
In all six cases, the GLP-1R scans successfully detected the insulinomas identified using conventional methods in four cases. By using a gamma-probe intraoperatively, GLP-1R detection permitted a successful surgical removal of the tumors in all patients, diagnosed histopathologically as five pancreatic and one extrapancreatic insulinomas. In vitro GLP-1R autoradiography showed a high density of GLP-1R in all tested insulinomas.


CONCLUSIONS
In vivo GLP-1R imaging is an innovative, noninvasive diagnostic approach that successfully localizes small insulinomas pre- and intraoperatively and that may in the future affect the strategy of insulinoma localization.
Christ
Emanuel
E
Division of Endocrinology, Inselspital, University Hospital of Bern, CH-3010 Bern, Switzerland.
Wild
Damian
D
Forrer
Flavio
F
Brändle
Michael
M
Sahli
Rahel
R
Clerici
Thomas
T
Gloor
Beat
B
Martius
Ferdinand
F
Maecke
Helmut
H
Reubi
Jean Claude
JC
D000328:Adult; D000368:Aged; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007205:Indium Radioisotopes; D007340:Insulinoma / Q000000981:diagnostic imaging*; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging; D018027:Receptors, Glucagon / Q000032:analysis*; D012680:Sensitivity and Specificity
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007205:Indium Radioisotopes; D018027:Receptors, Glucagon