Labeling and quality control of 188Re-lanreotide.
Lanreotide was labelled with 188Re obtained from 188W/188Re 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 degrees 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 NaCl 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% H2O (TFA 0.1%): 10% ACN (TFA 0.1%) up to 10% H2O (TFA 0.1%):90% ACN (TFA 0.1%) in 30 min, at flow 1 ml/min. Biodistribution in normal mice showed that 188Re-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 188Re-peptide bond by cysteine challenge test at 37 degrees 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 188Re from the complex. In vitro stability of 188Re-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.
Verdera
Silvia
S
Department of Radiopharmacy, Nuclear Research Center, Faculty of Sciences, Almirante Harwood 6199, 11500 Montevideo, Uruguay. sverdera@hotmail.com
Balter
Henia
H
Rodríguez
Graciela
G
Oliver
Patricia
P
Souto
Beatriz
B
López
Andrea
A
Goncalvez
Zulena
Z
D000818:Animals; D051379:Mice; D010456:Peptides, Cyclic / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000592:standards; D011786:Quality Control; D011868:Radioisotopes / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000592:standards; D019275:Radiopharmaceuticals / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000592:standards; D017481:Receptors, Somatostatin / Q000378:metabolism; D012211:Rhenium / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000592:standards; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000592:standards; D014018:Tissue Distribution
D010456:Peptides, Cyclic; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C060347:lanreotide; D013004:Somatostatin; D012211:Rhenium