title: Lanreotide labeled with 99mTc: preparation, preclinical testing and comparison with (111)In-DTPA-octreotide.
abstract: Somatostatin receptors are known to be present at a high density in a large number of tumors while (111)In-DTPA-octreotide has been routinely used in oncology for imaging somatostatin receptor-positive tumors and metastases. Lanreotide is another somatostatin receptor-specific peptide, shown to be effective in controlling the growth of some human tumors. The aim of this study was to label lanreotide with 99mTc by a direct labeling method and to evaluate the distribution and elimination characteristics of the labeled agent in rats. (111)In-octreotide was used as the reference radiopharmaceutical. For both radiolabeled-peptides the activity in blood and most organs decreased relatively rapidly with time. On the other hand, 99mTc-lanreotide was excreted mainly by the gastrointestinal tract to feces while (111)In-DTPA-octreotide was eliminated mostly into urine. The rat liver perfusion experiments showed that bile clearance of 99mTc-lanreotide was about three-order times higher than for (111)In-DTPA-octreotide. Analysis of the elimination mechanisms of 99mTc-lanreotide and (111)In-DTPA-octreotide in the perfused rat kidney confirmed that both peptides were eliminated mostly by glomerular filtration. Different protein binding of the agents ((111)In-DTPA-octreotide was only weakly bound, whereas 99mTc-lanreotide was strongly bound to proteins) resulted in substantially lower renal clearance of 99mTc-lanreotide when compared with (111)In-DTPA-octreotide. The results indicated that 99mTc-lanreotide could be of value for the scintigraphic imaging of specific tumors.
authors.affiliation: Faculty of Pharmacy, Charles University, Hradec Kralove, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Laznicek
authors.forename: Alice
authors.initials: A
authors.lastname: Laznickova
authors.forename: Frantisek
authors.initials: F
authors.lastname: Trejtnar
authors.forename: Petr
authors.initials: P
authors.lastname: Lorenc
authors.forename: Alexandra
authors.initials: A
authors.lastname: Varvarigou
authors.forename: Penelope
authors.initials: P
authors.lastname: Bouziotis
authors.forename: Spyros
authors.initials: S
authors.lastname: Archimandritis
mesh_terms: D000818:Animals; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D007700:Kinetics; D015282:Octreotide / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000493:pharmacokinetics*; D010456:Peptides, Cyclic / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D013004:Somatostatin / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D013667:Technetium / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D007205:Indium Radioisotopes; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; C060347:lanreotide; D013004:Somatostatin; D013667:Technetium; D004369:Pentetic Acid; D015282:Octreotide