Radiopharmacokinetic and dosimetric parameters of 188Re-lanreotide in athymic mice with induced human cancer tumors

• Published in: International journal of pharmaceutics 2006-03, Vol.310 (1), p.125-130
• Main Authors: Molina-Trinidad, Eva M., Murphy, Consuelo Arteaga de, Ferro-Flores, Guillermina, Murphy-Stack, Eduardo, Jung-Cook, Helgi
• Format: Article
• Language: English
• Subjects: 188Re-lanreotide; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Biological and medical sciences; Dosimetry; Female; General pharmacology; HeLa Cells; Humans; Implanted tumors in athymic mice; Injections, Intravenous; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Models, Animal; Neoplasm Transplantation; Neuroblastoma - metabolism; Neuroblastoma - pathology; OLINDA code; Peptides, Cyclic - administration & dosage; Peptides, Cyclic - pharmacokinetics; Pharmaceutical technology. Pharmaceutical industry; Pharmacokinetics; Pharmacology. Drug treatments; Radiation Dosage; Radioisotopes; Radiopharmaceuticals - administration & dosage; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Rhenium; Somatostatin - administration & dosage; Somatostatin - analogs & derivatives; Somatostatin - pharmacokinetics; Tissue Distribution; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2005.11.043

Radiolabeled peptides, like the somatostatin analogs, have been used for peptide receptor-mediated radionuclide therapy (PRMRT) in metastatic neuroendocrine tumors. The eight amino acid peptide 3-(2-naphthalenyl)- d-alanyl- l-cysteinyl- l-tyrosyl- d-tryptophyl- l-lysyl- l-valyl- l-cysteinyl- l-threoninamide,cyclic(2 → 7)-disulfide (9Cl) (lanreotide) was found to bind to the five somatostatin tumor receptors. Lanreotide has been labeled via the bifunctional chelating agent, DOTA, to 111In, and 90Y. A direct labeling method was used to label lanreotide with 188Re. Athymic mice with implanted human cancer tumors (uterine-cervix, renal, and neuroblastoma) were injected with radiochemically pure 188Re-lanreotide (1.11 MBq). The percent injected activity (%IA/g) from serial blood samples was the input data for the WinNonlin computer program to obtain radiopharmacokinetic parameters. The organs’ percent injected activity per gram of tissue (%IA/g) was extrapolated to the weights of a 70 kg male model organs and the number of nuclear transitions ( N) were the input for the OLINDA/EXM program to obtain dosimetry estimates. Induced uterine-cervix tumors (HeLa cells) show a mean 2.4 %IA/g uptake up to 24 h and the tumor/blood ratio was over 1.85 (1.5–24 h post-injection) confirming 188Re-lanreotide remains bound to the tumor. The estimated tumor absorbed dose was 460 mGy/MBq. Human effective dose was 0.0182 mSv/MBq. Therefore, 188Re-lanreotide is a good candidate for PRMRT and a clinical trial is being planned in order to acquire individual dosimetric data.