Labeling and quality control of 188Re-lanreotide.

Lanreotide was labelled with 1 8 8 Re obtained from 1 8 8 W/ 1 8 8 Re generator, using stannous ion as reducing agent, ascorbic acid as stabilizers and hydroxy ethylidene bisphosphonate (HEDP) as intermediary ligand at different molar ratios, pH and incubation times. Best yields (>95%) were obtained using molar ratios SnF2/lanreotide, ascorbic/lanreotide and HEDP/lanreotide of 40, 12 and 260, respectively, pH 1-2 with an incubation at 100°C for 30 min. Quality control evaluation and stability of the radiolabel compound was done by the following selected methods: chromatography in Whatman 3 MM with MEK and NaCI 0.15 M as solvents, ITLC-SG with ethanol-HCl 0.01N (90:10); reverse phase extraction cartridge (Sep-pak C18, Waters Associated) and RP-HPLC with radiometric and UV detection (220 nm) using MCH-5 n-capp column with linear gradient from 90% H 2 O (TFA 0.1%):10% ACN (TFA 0.1%) up to 10% H 2 O (TFA 0.1%):90% ACN (TFA 0.1%) in 30 min, at flow 1 ml/min. Biodistribution in normal mice showed that 1 8 8 Re-lanreotide is excreted mainly through the hepatobiliary system: more than 70% I.D. is present in gallbladder and intestines at 2 hr post injection. The stability of the 1 8 8 Re-peptide bond by cysteine challenge test at 37°C, during 2 and 24 hr of incubation time, reveals that approximately 300 and 100 molar ratio cys/peptide is required to displace 50% of the 1 8 8 Re from the complex. In vitro stability of 1 8 8 Re-lanreotide at room temperature (Rt) was demonstrated during 24 hr. Future works must be done in order to investigate its binding capacity to somatostatin receptors.