The non-invasive detection of
insulinomas remains a diagnostic problem that is not solved by means of
somatostatin receptor scintigraphy. We investigated the biokinetics and specificity of uptake and degradation of the
incretin hormone glucagon-like peptide-1 (GLP-1) in a rat
insulinoma cell line (RINm5F) in order to ascertain whether radiolabelled
GLP-1 may be suitable for specific visualisation of
insulinomas in vivo.
GLP-1 (7-36)amide was radioiodinated according to the
iodogen method. The specificity of the uptake of [(125)I]
GLP-1(7-36)
amide by RINm5F cells was investigated. Degradation products of
GLP-1 (7-36)amide in the cell medium were purified by HPLC. Their masses and amino acid sequences were determined by (252)Cf-plasma desorption mass spectrometry. Lysosomal degradation was inhibited and after differential centrifugation the amount of radiotracer incorporated into lysosomes was determined. Biodistribution studies were performed in a rat
insulinoma model (NEDH rats and RINm5F cells) with [(123)I]
GLP-1(7-36)
amide and its more stable agonist [(123)I]
exendin 3. The uptake of radiotracer into
insulinoma cells reached a maximum within 5 min. It was inhibited by an excess of unlabelled
peptide. [(125)I]
GLP-1(7-36)
amide accumulated in the cells if lysosomal degradation was inhibited. Degradation products of the
peptide were found in the cell medium. We determined their mass and derived their amino acid sequence. Radiolabelling of
exendin 3 was more difficult than that of
GLP-1 because of the lack of
tyrosine in its primary structure. Biodistribution studies showed rapid blood clearance and uptake of the radiotracer into the tumour and the pancreas. It was also possible to detect
insulinomas in an animal model by external scintigraphy using radioiodinated
GLP-1 (7-36)amide and
exendin 3.
GLP-1 (7-36)amide is specifically internalised into
insulinoma cells by a receptor-mediated mechanism. Our results demonstrate that
GLP-1 receptor-directed scintigraphy may be a new method for the detection of
insulinomas in vivo. Due to the short half-life of
GLP-1, its more stable analogue
exendin 3 may better suit this purpose in vivo.